Patent Publication Number: US-2023146253-A1

Title: Methods related to bronchial premalignant lesion severity and progression

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional under 35 U.S.C. § 121 of co-pending U.S. Ser. No. 16/545,032 filed Aug. 20, 2019, which claims benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 62/765,264 filed Aug. 20, 2018, the contents of which are incorporated herein by reference in their entireties. 
    
    
     GOVERNMENT SUPPORT 
     This invention was made with Government Support under Contract No. CA196408 awarded by the National Institutes of Health. The Government has certain rights in the invention. 
    
    
     TECHNICAL FIELD 
     The technology described herein relates to treatment, diagnosis, and monitoring of treatment for bronchial premalignant lesions. 
     BACKGROUND 
     Lung squamous cell cancer develops from non-cancerous lesions in the airway known as bronchial premalignant lesions. The presence of persistent or progressive dysplastic bronchial premalignant lesions is a marker of increased lung cancer risk both at the lesion site (where they are the presumed precursors of squamous cell lung cancer) and elsewhere in the lung. Not all bronchial premalignant lesions progress to invasive cancer, and those that do, progress at variable rates with variable outcomes. At present, there are no tools available in the clinic to identify which lesions will progress to cancer and which will not. Additionally, the current technology for detecting bronchial premalignant lesions is via autofluorescence and white-light bronchoscopy. A bronchoscopy procedure is invasive and is only moderately sensitive and specific at detecting small bronchial premalignant lesions as it requires visualization of the lesions. Finally, to date, the only treatment for bronchial premalignant lesions is to remove the lesions via surgery or bronchoscopy. 
     SUMMARY 
     The inventors have now developed: 1) tests for the presence of bronchial premalignant lesions (some of which do not require bronchoscopy and use the surprising finding that normal tissues elsewhere in the airway exhibit biomarkers indicating the presence of bronchial premalignant lesions in the subject), 2) methods for determining if the bronchial premalignant lesions is likely to progress to cancer, 3) new therapies for bronchial premalignant lesions which target the underlying molecular changes which characterize the bronchial premalignant lesions. 
     Accordingly, provided herein one aspect is a method of treating bronchial premalignant lesions, the method comprising: administering at least one of: (i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; (ii) at least every 6 months, one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or (iii) at least one anti-proliferative drug; to a subject determined to have at least one of: (a) an increased level of expression of at least one module 5 gene as compared to a non-proliferative lesion reference level; and (b) a decreased level of expression of at least one module 6 gene as compared to a non-proliferative lesion reference level. 
     In one embodiment of this aspect and all other aspects provided herein, the at least one module 5 gene is selected from the group consisting of: RACGAP1 and TPX2; and the at least one module 6 gene is selected from the group consisting of: NEK11 and IFT88. 
     In another embodiment of this aspect and all other aspects provided herein, the subject is further determined to have an increased level of expression of at least one module 7 or module 4 gene. 
     In another embodiment of this aspect and all other aspects provided herein, the at least one module 7 or module 4 gene is selected from the group consisting of: COX6A1; COX7A2; RPL26; and RPL23. 
     In another embodiment of this aspect and all other aspects provided herein, the level of expression of each of the genes of Table 15 is determined. The method of any of claims  1 - 5 , wherein the at least one anti-proliferative drug is selected from the group consisting of: Acetylcholine receptor antagonist; Acetylcholinesterase inhibitors; Adenosine receptor antagonists; Adrenergic receptor antagonists; AKT inhibitors; Angiotensin receptor antagonists; Apoptosis stimulants; Aurora kinase inhibitors; CDK inhibitors; Cyclooxygenase inhibitors; Cytokine production inhibitors; Dehydrogenase inhibitors; DNA protein kinase inhibitors; focal adhesion inhibitors; Dopamine receptor antagonist; EGFR inhibitors; ERK1 and ERK2 phosphorylation inhibitors; Estrogen receptor agonists; EZH2 inhibitors; FLT3 inhibitors; Glucocorticoid receptor agonists; Glutamate receptor antagonists; HDAC inhibitors; Histamine receptor antagonists; Histone lysine methyltransferase inhibitors; HSP inhibitors; IKK inhibitors; Ion channel antagonists; JAK inhibitors; JNK inhibitors; KIT inhibitors; Leucine rich repeat kinase inhibitors; MDM inhibitors; mediator release inhibitors; MEK inhibitors; MTOR inhibitors; Monoamine oxidase inhibitors; NFkB pathway inhibitors; nucleophosmin inhibitors; PARP inhibitors; PPAR receptor agonists; PI3K inhibitors; tyrosine kinase inhibitors; Phosphodiesterase inhibitors; protein kinase inhibitors; RAF inhibitors; RNA polymerase inhibitors; topoisomerase inhibitors; RNA synthesis inhibitors; SIRT inhibitors; sodium channel blockers; VEGFR inhibitors; and Vitamin D receptor agonists. 
     In another embodiment of this aspect and all other aspects provided herein, the anti-proliferative drug is administered as an inhaled formulation or topical formulation. 
     In another embodiment of this aspect and all other aspects provided herein, the anti-proliferative drug is administered during a bronchoscopy-based procedure. 
     In another embodiment of this aspect and all other aspects provided herein, the anti-proliferative drug is administered systemically. 
     In another embodiment of this aspect and all other aspects provided herein, the anti-proliferative drug is administered during a bronchoscopy-based procedure and systemically. 
     Another aspect provided herein relates to a method of treating bronchial premalignant lesions, the method comprising: administering at least one of: (i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; (ii) at least every 6 months, one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or (iii) at least one anti-proliferative drug; to a subject determined to have at least one of: (a) an increased level of expression of at least one module 5 gene as compared to a non-proliferative lesion reference level; and (b) a decreased level of expression of at least one module 6 gene as compared to a non-proliferative lesion reference level, wherein the subject is further determined to have a decreased level of expression of at least one module 9 gene as compared to a non-proliferative lesion reference level and/or an increased level of expression of at least one module 10 gene as compared to a non-proliferative lesion reference level. 
     In one embodiment of this aspect and all other aspects provided herein, the subject determined to have a decreased level of expression of at least one module 9 gene and/or an increased level of expression of at least one module 10 gene is administered at least one of:
         i. both a bronchoscopy-based procedure to survey the central airway wherein the lesions are biopsied to remove abnormal tissue and a chest CT scan;   ii. at least every 6 months, one of a bronchoscopy-based procedure to survey the central airway wherein the lesions are biopsied to remove abnormal tissue and a chest CT scan; and/or   iii. at least one immune stimulating drug.       

     Also provided herein, in another aspect, is a method of treating bronchial premalignant lesions, the method comprising: administering at least one of: (i) both a bronchoscopy-based procedure to survey the central airway wherein the lesions are biopsied to remove abnormal tissue and a chest CT scan; (ii) at least every 6 months, one of a bronchoscopy-based procedure to survey the central airway wherein the lesions are biopsied to remove abnormal tissue and a chest CT scan; and/or (iii) at least one immune stimulating drug; to a subject determined to have a decreased level of expression of at least one module 9 gene as compared to a non-proliferative lesion reference level and/or an increased level of expression of at least one module 10 gene as compared to a non-proliferative lesion reference level. 
     In one embodiment of this aspect and all other aspects provided herein, the module 9 gene is selected from the group consisting of: EPSTI1; UBE2L6; B2M and TAP1. 
     In another embodiment of this aspect and all other aspects provided herein, the at least one gene module 9 gene is selected from Table 16. 
     In another embodiment of this aspect and all other aspects provided herein, the module 10 gene is selected from the group consisting of: CACNB3 and MAPK10. 
     In another embodiment of this aspect and all other aspects provided herein, the at least one immune stimulating drug is selected from the group consisting of: immune-checkpoint inhibitors (e.g. inhibitors against, PD-1, PD-L1, CTLA4, and LAG3); drugs that stimulate interferon signaling (e.g. anti-viral drugs that improve interferon signaling); DNA synthesis inhibitors; IMDH inhibitors; CDK inhibitors; ribonucleotide reductase inhibitors; dihydrofolate reductase inhibitors; topoisomerase inhibitors; FLT3 inhibitors; IGF-1 inhibitors; MEK inhibitors; aurora kinase inhibitors; PKC inhibitors; RAF inhibitors; PDFGR/KIT inhibitors; VEGFR inhibitors; SRC inhibitors; retinoid receptor agonists; HDAC inhibitors; DNA methyltransferase inhibitors; and EZH2 inhibitors. 
     Another aspect provided herein relates to a method of treating bronchial premalignant lesions, the method comprising: administering at least one of: (i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; (ii) at least every 6 months, one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or (iii) at least one anti-inflammatory drug; to a subject determined to have at least one of: (a) an increased level of expression of at least one module 2 gene as compared to a non-inflammatory reference level; and (b) a decreased level of expression of at least one module 6 gene as compared to a non-inflammatory reference level. 
     In one embodiment of this aspect and all other aspects provided herein, the at least one module 2 gene is selected from the group consisting of: MSANTD2, CCNL2, and LUC7L; and the at least one module 6 gene is selected from the group consisting of: NEK11 and IFT88. 
     In another embodiment of this aspect and all other aspects provided herein, the subject is further determined to have an increased level of expression of at least one module 7 gene, module 1 gene, or module 8 gene and/or decreased level of expression of at least one module 4 gene or one module 5 gene. 
     In another embodiment of this aspect and all other aspects provided herein, the at least one module 7 gene is selected from the group consisting of: RPL26 and RPL23. 
     In another embodiment of this aspect and all other aspects provided herein, the at least one module 1 gene is selected from the group consisting of: KIRREL; PHLDB1; and MARVELD1. 
     In another embodiment of this aspect and all other aspects provided herein, the at least one module 8 gene is selected from the group consisting of: DOC2; CD53; and LAP™. 
     In another embodiment of this aspect and all other aspects provided herein, the at least one module 4 gene is selected from the group consisting of: COX6A1 and COX7A2 
     In another embodiment of this aspect and all other aspects provided herein, the at least one module 5 gene is selected from the group consisting of: RACGAP1 and TPX2 
     In another embodiment of this aspect and all other aspects provided herein, the level of expression of each of the genes of Table 15 is determined. 
     In another embodiment of this aspect and all other aspects provided herein, the at least one anti-inflammatory drug is selected from the group consisting of: Acetylcholine receptor antagonists; Acetylcholinesterase inhibitors; Adenosine receptor antagonists; Adrenergic receptor antagonists; Angiotensin receptor antagonists; Anti-IL1B antibodies; Apoptosis stimulants; Aurora kinase inhibitors; CDK inhibitors; Cyclooxygenase inhibitors; Cytokine production inhibitors; Dehydrogenase inhibitors; Dopamine receptor antagonists; EGFR inhibitors; ERK1 and ERK2 phosphorylation inhibitors; Estrogen receptor agonists; FLT3 inhibitors; Glucocorticoid receptor agonists; Glutamate receptor antagonists; HDAC inhibitors; Histamine receptor antagonists; Histone lysine methyltransferase inhibitors; HSP inhibitors; IKK inhibitors; Ion channel antagonists; KIT inhibitors; Leucine rich repeat kinase inhibitors; MEK inhibitors; MDM inhibitors; Phosphodiesterase inhibitors; Monoamine oxidase inhibitors; MTOR inhibitors; NFkB pathway inhibitors; nucleophosmin inhibitors; PARP inhibitors; PI3K inhibitors; PPAR receptor agonists; protein synthesis inhibitors (e.g. chloramphenicol); RAF inhibitors; SIRT inhibitors; Sodium channel blockers; TGF beta receptor inhibitors; Topoisomerase inhibitors; Tyrosine kinase inhibitors; VEGFR inhibitors; and Vitamin D receptor agonists. 
     In another embodiment of this aspect and all other aspects provided herein, the anti-inflammatory drug is administered during a bronchoscopy-based procedure. 
     In another embodiment of this aspect and all other aspects provided herein, the anti-inflammatory drug is administered systemically. 
     In another embodiment of this aspect and all other aspects provided herein, the anti-inflammatory drug is administered during a bronchoscopy-based procedure and systemically. 
     In another embodiment of this aspect and all other aspects provided herein, the at least one gene is selected from Table 14. 
     In another embodiment of this aspect and all other aspects provided herein, the level of expression of each of the genes of Table 14 is determined. 
     In another embodiment of this aspect and all other aspects provided herein, whereby the development of lung cancer lung squamous cell carcinoma is prevented, delayed, or slowed. 
     In another embodiment of this aspect and all other aspects provided herein, wherein the lung cancer is lung squamous cell carcinoma. 
     In another embodiment of this aspect and all other aspects provided herein, the level of expression is the level of expression in an endobronchial biopsy, endobronchial brushing sample, large airway biopsy, large airway brushing sample, nasal epithelial cells, sputum, or blood obtained from the subject. 
     In another embodiment of this aspect and all other aspects provided herein, the level of expression is the level of expression in a bronchial brushing obtained from the right or left mainstem bronchus. 
     In another embodiment of this aspect and all other aspects provided herein, the biopsy or brushing sample comprises morphologically-normal tissues or cells. 
     In another embodiment of this aspect and all other aspects provided herein, the biopsy or brushing sample consists of morphologically-normal tissues or cells. 
     In another embodiment of this aspect and all other aspects provided herein, the level of expression is the level of expression in a sample comprising bronchial premalignant lesion cells. 
     In another embodiment of this aspect and all other aspects provided herein, the level of expression is the level of expression in a sample comprising morphologically-normal cells. 
     In another embodiment of this aspect and all other aspects provided herein, the subject is a smoker or former smoker. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS.  1 A- 1 E  demonstrate that endobronchial biopsies divide into four distinct molecular subtypes that correlate with clinical and molecular phenotypes. ( FIG.  1 A ) Genes (n=3,936) organized into 9 gene co-expression modules were used to discover four molecular subtypes (Proliferative, Inflammatory, Secretory, and Normal-like) across the 190 DC biopsies using consensus clustering. The heatmap shows semi-supervised hierarchal clustering of z-score normalized gene expression across the 3,936 genes and 190 DC biopsies. The top bar represents the four molecular subtypes: Proliferative (n=52 samples), Inflammatory (n=37 samples), Secretory (n=61 samples), and Normal-like (n=40 samples). Throughout all figures, the four molecule subtypes are represented by four shades of grey, increasing in lightness respective to the order given in the previous sentence. On the left side of the heatmap, the mean of the first principal component calculated across module genes is plotted for each subtype. On the right side of the heatmap, a summary of enriched biological pathways is listed for each module. ( FIG.  1 B ) Bubbleplots showing significant associations (p&lt;0.01 by Fisher&#39;s Exact Test) between the molecular subtypes and smoking status, biopsy histological grade, and the predicted LUSC tumor molecular subtypes. The columns represent the 4 molecular subtypes (Proliferative, Inflammatory, Secretory, and Normal-like) and the diameter of the circle is proportional to the number of samples within each subtype that have the row phenotype. ( FIG.  1 C ) Boxplot of expression values of MKI67 in biopsies with normal or hyperplasia histology (n=8, 16, 26, 18 in Proliferative, Inflammatory, Secretory, and Normal-like subtypes, respectively). The MKI67 expression levels of the Proliferative subtype are significantly greater than non-Proliferative subtype samples (FDR=3.4e-10) ( FIG.  1 D ) Boxplot of expression values of MKI67 in biopsies with dysplastic histology (n=33, 11, 19, 9 in Proliferative, Inflammatory, Secretory, and Normal subtypes, respectively). The MKI67 expression levels of the Proliferative subtype are significantly greater than non-Proliferative subtype samples (FDR=3.1e-8). ( FIG.  1 E ) Immunofluorescent staining demonstrating the increased MKI67 and KRT5 staining and reduced TUB1A1 staining in the Proliferative subtype in concordance with the expression of the corresponding marker genes. The representative samples shown for the Proliferative and Inflammatory subtypes have dysplasia histology while the samples shown for the Secretory and Normal-like subtypes have normal histology (Magnification 200×). 
         FIGS.  2 A- 2 D  demonstrate that phenotypic associations with the molecular subtypes are confirmed in an independent sample set. ( FIG.  2 A ) The 190 DC biopsies and the 3,936 genes were used to build a 22-gene nearest centroid molecular subtype classifier. Semi-supervised hierarchal clustering of z-score normalized gene expression across the 22 classifier genes and 190 DC biopsies training samples. ( FIG.  2 B ) The 22-gene nearest centroid molecular subtype classifier was used to predict the molecular subtypes of the 105 VC biopsies. Semi-supervised hierarchal clustering of z-score normalized gene expression across 22 genes and 105 VC is plotted. The rows of the heatmap give the gene name and module membership, and the column color bar shows molecular subtype membership. ( FIG.  2 C ) Bubbleplots showing significant associations (p&lt;0.01 by Fisher&#39;s Exact Test) between the VC molecular subtypes and smoking status, biopsy histological grade, and the predicted LUSC tumor molecular subtypes. The columns represent the 4 molecular subtypes (Proliferative, Inflammatory, Secretory, and Normal) and the radius of the circle is proportional to the number of samples within each subtype that have the row phenotype. ( FIG.  2 D ) Bubbleplots showing significant associations (p&lt;0.01 by Fisher&#39;s Exact Test) between the VC molecular subtypes and smoking status, biopsy histological grade, and the predicted LUSC tumor molecular subtypes. The columns represent the 4 molecular subtypes (Proliferative, Inflammatory, Secretory, and Normal-like) and the radius of the circle is proportional to the number of samples within each subtype that have the row phenotype. 
         FIGS.  3 A- 3 C  demonstrate the performance of the molecular subtype classifier in the large airway brushes from normal appearing epithelium sampled at the same time as the endobronchial biopsies. ( FIG.  3 A ) The DC (left) and VC (right) cohorts, showing the number of brushes (y-axis) predicted to be positive for the Proliferative subtype that have at least one biopsy (y-axis) with a classification of the Proliferative subtype at the time the brush was sampled. ( FIG.  3 B ) Boxplots of PC1 for Modules 4, 5, 6, and 7 (y-axis) across the four molecular subtypes for each cohort (x-axis). The asterisk indicates significant differences between the Proliferative subtype versus all other samples (FDR&lt;0.05). ( FIG.  3 C ) Boxplots of PC1 for Modules 4, 5, 6, and 7 (y-axis) across the four molecular subtypes for each cohort (x-axis). The asterisk indicates significant differences between the Proliferative subtype versus all other samples (FDR&lt;0.05). 
         FIGS.  4 A- 4 H  demonstrate that the module enriched for interferon signaling and antigen processing is associated with biopsy progression/persistence and a depletion of innate and adaptive immune cells in the Proliferative subtype. ( FIGS.  4 A and  4 F ) Metagene expression of Module 9 genes among DC biopsies within the Proliferative subtype (p=0.002 between the progressive/persistent versus regressive biopsies). Biopsy progression/regression was defined for each biopsy based on the histology of the biopsy and the worst histology recorded for the same lung anatomic location in the future. Histology changes between normal, hyperplasia, and metaplasia were classified as “normal stable”, decreases in histological dysplasia grade or changes from dysplastic histology to normal/hyperplasia/metaplasia were classified as “regressive”, lack of future histological data was classified as “unknown”, and everything else was classified as “progressive/persistent.” ( FIGS.  4 B and  4 G ) Boxplot of the percentages of CD68 and CD163, CD68, CD163, CD4, and CD8 positively stained cells between progressive/persistent and regressive biopsies (p&lt;0.001 for all comparisons). The x-axis labels indicate the number of regions (R) enumerated across (P) subjects for each stain and outcome group depicted in the boxplot. Biopsies were included in the analysis if their clinical outcome was concordant with the Module 9 score. ( FIG.  4 B ) Metagene expression of Module 9 genes among VC biopsies within the Proliferative subtype (p=0.03 between the progressive/persistent versus regressive biopsies). ( FIG.  4 C ) Top: Z-score normalized gene expression across the 112 genes in Module 9 and the DC biopsies (left) and the VC biopsies (right). Each heatmap is supervised according to the Module 9 GSVA scores. Top bars indicate the histological grade of the biopsies and their progression status. Bottom: xCell results indicating the relative abundance of immune cell types across the DC biopsies (left) and the VC biopsies (right). Immune cell types displayed are significantly associated with lesion progressive/persistence (FDR&lt;0.05 in both the DC and VC after adjusting for differences in epithelial cell content). ( FIG.  4 D ) Representative histology where the dashed line denoted the separate of epithelium and stromal compartment Top panels: A progressive severe dysplasia has reduced presence of immune cells demonstrated by the marked reduction in expression of M2 macrophages (CD68/163 staining, double positive cells indicated by the arrows) and CD8 T cells. (sample corresponds to *P in  FIG.  4 C .) Bottom panels: A regressive moderate dysplasia has increased presence of immune cells including M2 macrophages (CD68/163 staining double positive cells indicated by the arrows) and CD8 T cells. (samples correspond to *R in  FIG.  4 C .) ( FIGS.  4 E and  4 H ) Boxplots of the percentages of CD68 and CD163, CD68, CD163, CD4, and CD8 positively stained cells between progressive/persistent and regressive biopsies (p&lt;0.001 for all comparisons). The x-axis labels indicate the number of regions (R) enumerated across (P) subjects for each stain and outcome group depicted in the boxplot. Biopsies were included in the analysis if their clinical outcome was concordant with the Module 9 score. 
         FIG.  5    depicts Batch Information and Alignment Statistics on Samples in both the Discovery and Validation cohorts. Statistical tests between the Discovery and Validation cohorts were performed using Fisher&#39;s Exact Test for categorical variables and Student&#39;s T-Test for continuous variable. Percentages are reported for categorical variables and mean and standard deviations are reported for continuous variables. 
         FIG.  6    depicts a summary of Gene Modules. The module number, number of genes in the module, biological pathways and select genes associated with the module, and an FDR value for the difference in GSVA scores for the module between the molecular subtypes are reported. 
         FIG.  7    depicts a List of Samples used for Immunofluorescence Studies. 
         FIG.  8    depicts the distribution of Molecular Subtypes by Subject. The columns represent the 4 molecular subtypes (Proliferative, Inflammatory, Secretory, and Normal-like) and the radius of the circle is proportional to the number of samples within each subtype. 
         FIG.  9    depicts a graph of Immunofluorescent Staining Quantitation of Proliferation, Basal Cell, and Ciliated Cell Markers across the Molecular Subtypes. Boxplot of immunofluorescent staining quantitation of KI67 (proliferation), KRT5 (basal cell) and TUB1A1 (ciliated cell) across representative samples from each molecular subtype (Proliferative n=4, Inflammatory n=3, Secretory n=1, Normal-like n=1). KI67 and KRT5 staining are significantly higher in samples in the Proliferative subtype (p=0.02 and p=0.01, respectively, for sample differences between the Proliferative subtype and other subtypes). TUB1A1 was lower in samples in the Proliferative and Inflammatory subtypes but did not reach statistical significance (p=0.07 for sample differences between Proliferative and Inflammatory subtypes versus Inflammatory and Secretory subtypes). 
         FIGS.  10 A- 10 H  depict boxplots of Select Genes and Cell Type Deconvolution Results across the Discovery and Validation Cohorts by Molecular Subtype. ( FIGS.  10 A- 10 D ) Discovery cohort biopsies. ( FIGS.  10 E- 10 H ) Validation cohort biopsies. ( FIG.  10 A ) and ( FIG.  10 E ) show boxplots of gene expression levels of LUSC driver genes identified by TCGA across the molecular subtypes. ( FIG.  10 B ) and ( FIG.  10 F ) show boxplots of gene expression levels of cell type marker genes across the molecular subtypes. ( FIG.  10 C ) and ( FIG.  10 G ) show boxplots of GSVA scores calculated using Dvorak et al. gene sets across the molecular subtypes. ( FIG.  10 D ) and ( FIG.  10 H ) show boxplots of ESTIMATE algorithm scores across the molecular subtypes. The ESTIMATE algorithm estimates the stromal (StromalScore), immune (ImmuneScore), and epithelial (ESTIMATEScore) cell fractions in each sample. High immune and stromal scores indicate a high fraction of stromal and immune cells while low epithelial scores indicate a high fraction of epithelial cells. 
         FIG.  11    depicts a heatmap of the 22-gene Molecular Subtype Classifier in the Discovery and Validation Cohort Biopsies. Semi-supervised hierarchal clustering of z-score normalized residual gene expression across the 22 classifier genes and 190 DC biopsies training samples (left) and the 105 VC biopsies (right). The rows of the heatmap show the gene module membership. The first column color bar shows molecular subtype membership in the DC and the 22-gene predict subtype membership in the VC. The second column color bar depicts correct and incorrect predictions in the DC using the 22-gene classifier and molecular subtypes derived by performing consensus clustering across the VC. 
         FIG.  12    depicts graphs of gene module behavior across the Molecular Subtypes in the Discovery and Validation Cohort Biopsies. The mean of the first principal component calculated across module genes is plotted for each molecular subtype. 
         FIG.  13    depicts the concordance between Module 9 and two Cell Type Deconvolution Analyses. Top: Hierarchal clustering of z-score normalized gene expression across the 112 genes in module 9 and the DC biopsies (left) and the VC biopsies (right). Each heatmap is supervised according to the module 9 GSVA scores. Top bars indicate the histological grade of the biopsies and their progression status. xCell results (Middle) and GSVA scores for gene sets described by Bindea et al. (Bottom) indicating the relative abundance of immune cell types across the DC biopsies (left) and the VC biopsies (right). Immune cell types displayed are significantly associated with lesion progression/persistence (FDR&lt;0.05 in both the DC and VC). 
         FIG.  14    depicts a tracheobronchial map of the locations of the sites sampled by endobronchial biopsy. 
         FIG.  15    depicts the distribution of subject among the discovery cohort endobronchial biopsies across the four molecular subtypes. Genes (n=3,936) organized into 9 gene co-expression modules were used to discover four molecular subtypes (Proliferative, Inflammatory, Secretory, and Normal-like) across the 190 discovery cohort (DC) biopsies using consensus clustering. The heatmap shows semi-supervised hierarchal clustering of z-score normalized gene expression across the 3,936 genes and 190 DC biopsies. The top color bars represent the subject the sample was derived and molecular subtype membership: Proliferative (n=52 samples), Inflammatory (n=37 samples), Secretory (n=61 samples), and Normal-like (n=40 samples). On the left side of the heatmap, the mean module GSVA score is plotted for each subtype. 
         FIG.  16    depicts the molecular subtype distribution for each subject across bronchoscopy procedures. The barplot shows for each subject and each bronchoscopy procedure the number of biopsies sampled and their corresponding molecular subtype. The y-axis indicates the subject number and whether or not that subject had a prior history of either lung squamous cell carcinoma (LUSC) or another type of lung cancer (Other). The discovery cohort includes subjects 1 through 32 and the validation cohort includes subjects 33 through 52. We did not detect a difference in the diversity of subtype classifications within a subject based on prior history of lung cancer (mean Shannon entropy of subtype classifications within patients with a history of lung cancer=1.12, n=32 vs. patients without a history of lung cancer=1.25, n=17; Wilcoxon Rank Sum test p-value=0.43). 
     
    
    
     DETAILED DESCRIPTION 
     As described herein, the inventors have discovered that premalignant lesions in the airway of a subject can be characterized as being one of five: types: normal-like, secretory, inflammatory, progressive proliferative, and persistent proliferative. Identifying the premalignant lesion as one of these types permits more effective treatment of the subject, as different types of lesions will be responsive to different treatments and require different treatment and monitoring regimes. Accordingly, provided herein are methods of treatment relating to the treatment of bronchial premalignant lesions in a subject. Such methods can comprise assays, tests, and/or identification of the lesion type and administration of therapeutic regimens appropriate for that lesion type. 
     As used herein, “premalignant lesion” refers to an epithelial lesion or dysplasia which is a precursor or can be a precursor to cancer. The basement membrane is intact with no possibility of metastatic spread, as opposed to cancer. A bronchial premalignant lesion is a premalignant lesion present in the bronchial epithelium of a subject. Bronchial premalignant lesions are typically small and can be difficult to visualize using conventional white light bronchoscopy. 
     The bronchial premalignant lesions can exhibit one of five phenotypes described herein, namely progressive proliferative, persistent proliferative, secretory, inflammatory, and normal-like. The subtype names reference the key differences in molecular pathway activity which differentiate the subtypes from each other. The different phenotypes of lesion can be distinguished from each other and from normal tissue by use of the gene expression patterns described herein. As explained in detail elsewhere herein, the gene expression patterns identified herein relate to 10 modules of genes, where each module is a group of genes with similar expression patterns across the different bronchial premalignant lesion subtypes. The identity of each of the modules, e.g. the genes that comprise each module, are provided in Table 13 herein. Briefly, proliferative lesions (both progressive and persistent) are distinguished by having increased module 4, 5, and 7 expression and decreased module 6 expression. Progressive proliferative lesions can be distinguished from persistent proliferative lesions in that they have decreased module 9 expression and/or increased module 10 expression. Secretory lesions are distinguished by an increase in module 6 expression and a decrease in module 1 expression and optionally, an increase in module 8 expression and a decrease in modules 2, 5, and 7 expression. Normal-like subtype is distinguished by an increase in module 6 expression and a decrease in module 9 expression and optionally, an increase in module 1 expression and a decrease in module 8 expression. 
     Standard treatment for subjects at risk of lung cancer, or who have been identified to have bronchial premalignant lesions, is annual screening for lung cancer (e.g. a bronchoscopy and/or chest CT scan). When a subject has a proliferative bronchial premalignant lesion, such treatment is no longer sufficient and the subject should be treated more aggressively. Accordingly, in one aspect of any of the embodiments, provided herein is a method of treating bronchial premalignant lesions, the method comprising administering at least one of: i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; ii) at least every 6 months, at least one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or iii) at least one anti-proliferative drug to a subject determined to have at least one of a) an increased level of expression of at least one module 5 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level. In one aspect of any of the embodiments, provided herein is a method of treating bronchial premalignant lesions, the method comprising determining a subject as to have at least one of a) an increased level of expression of at least one module 5 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level and administering at least one of: i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; ii) at least about every 6 months (e.g., at least every 1, 2, 3, 4, 5, or 6 months), at least one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or iii) at least one anti-proliferative drug to the subject. In some embodiments of any of the aspects, the reference level is a non-proliferative reference level. 
     In some embodiments, if the subject is determined not to have at least one of a) an increased level of expression of at least one module 5 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level, the subject is not administered an anti-proliferative drug and is administered a bronchoscopy-based procedure to survey the central airway and/or a chest CT scan no more frequently than every 6 months (e.g., no more frequently than every 6, 7, 8, 9, 10, 11, or 12 months). In some embodiments, if the subject is determined not to have a) an increased level of expression of at least one module 5 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level, the subject is not administered an anti-proliferative drug and is administered a bronchoscopy-based procedure to survey the central airway and/or a chest CT scan no more frequently than every 6 months (e.g., no more frequently than every 6, 7, 8, 9, 10, 11, or 12 months). 
     Module 5 and 6 gene expression, in a bronchial brushing sample, is sufficient to identify a subject having a proliferative subtype lesion. This avoids the need to visualize and/or sample the actual lesion. Accordingly, in one aspect of any of the embodiments, provided herein is a method of treating bronchial premalignant lesions, the method comprising administering at least one of: i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; ii) at least every 6 months, at least one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or iii) at least one anti-proliferative drug to a subject determined to have, in a bronchial brushing sample, a) an increased level of expression of at least one module 5 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level. In one aspect of any of the embodiments, provided herein is a method of treating bronchial premalignant lesions, the method comprising determining a subject to have, in a bronchial brushing sample obtained from the subject, a) an increased level of expression of at least one module 5 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level and administering at least one of: i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; ii) at least every 6 months, at least one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or iii) at least one anti-proliferative drug to the subject. In some embodiments of any of the aspects, the reference level is a non-proliferative reference level. In some embodiments of any of the aspects, the bronchial brushing is taken from a morphologically-normal location in the right or left mainstem bronchus. In some embodiments of any of the aspects, the bronchial brushing is taken from a visually-normal location in the right or left mainstem bronchus. 
     Module 5 and 6 genes are provided in Table 13. The at least one module 5 gene and/or module 6 gene can be any one or more of the module 5 and 6 genes listed in Table 13. 
     In some embodiments of any of the aspects, the level of expression of at least one module 5 gene or at least one module 6 gene is determined. In some embodiments of any of the aspects, the level of expression of two or more module 5 genes or two or more module 6 genes is determined. In some embodiments of any of the aspects, the level of expression of each module 5 gene or each module 6 gene of Table 13 is determined. 
     In some embodiments of any of the aspects, the level of expression of at least one module 5 gene and at least one module 6 gene is determined. In some embodiments of any of the aspects, the level of expression of two or more module 5 genes and two or more module 6 genes is determined. In some embodiments of any of the aspects, the level of expression of each module 5 gene and each module 6 gene of Table 13 is determined. 
     In some embodiments of any of the aspects, the at least one module 5 gene comprises or is RACGAP1 or TPX2. In some embodiments of any of the aspects, the at least one module 5 gene comprises or is RACGAP1 and TPX2. In some embodiments of any of the aspects, the at least one module 6 gene comprises or is NEK11 or IFT88. In some embodiments of any of the aspects, the at least one module 6 gene comprises or is NEK11 and IFT88. 
     The proliferative subtype is further distinguished by increased expression of module 7 and/or 4. Accordingly, in some embodiments of any of the aspects, the subject is further determined to have an increased level of expression of at least one module 7 or module 4 gene as compared to a reference level. In some embodiments of any of the aspects, the subject is further determined to have an increased level of expression of at least one module 7 and at least one module 4 gene as compared to a reference level. In some embodiments of any of the aspects, the reference level is a non-proliferative reference level. 
     Module 4 and 7 genes are provided in Table 13. The at least one module 4 gene and/or module 7 gene can be any one or more of the module 4 and 7 genes listed in Table 13. 
     In some embodiments of any of the aspects, the level of expression of at least one module 4 gene or at least one module 7 gene is determined. In some embodiments of any of the aspects, the level of expression of two or more module 4 genes or two or more module 7 genes is determined. In some embodiments of any of the aspects, the level of expression of each module 4 gene or each module 7 gene of Table 13 is determined. 
     In some embodiments of any of the aspects, the level of expression of at least one module 4 gene and at least one module 7 gene is determined. In some embodiments of any of the aspects, the level of expression of two or more module 4 genes and two or more module 7 genes is determined. In some embodiments of any of the aspects, the level of expression of each module 4 gene and each module 7 gene of Table 13 is determined. 
     In some embodiments of any of the aspects, the at least one module 4 gene comprises or is COX6A1 or COX7A2. In some embodiments of any of the aspects, the at least one module 4 gene comprises or is COX6A1 and COX7A2. In some embodiments of any of the aspects, the at least one module 7 gene comprises or is RPL26 or RPL23. In some embodiments of any of the aspects, the at least one module 7 gene comprises or is RPL26 and RPL23. 
     When a subject has a progressive proliferative bronchial premalignant lesion, aggressive treatment, even beyond that provided for proliferative bronchial premalignant lesion, can be indicated. Accordingly, in one aspect of any of the embodiments, provided herein is a method of treating bronchial premalignant lesions, the method comprising administering at least one of: i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; ii) at least every 6 months, at least one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; iii) at least one immune stimulating drug and/or iv) at least one immune stimulating drug and at least one anti-proliferative drug to a subject determined to have a decreased level of expression of at least one module 9 gene as compared to a reference level and/or an increased level of expression of at least one module 10 gene as compared to a reference level. In one aspect of any of the embodiments, provided herein is a method of treating bronchial premalignant lesions, the method comprising a) determining a subject as to have a decreased level of expression of at least one module 9 gene as compared to a reference level and/or an increased level of expression of at least one module 10 gene as compared to a reference level and b) administering at least one of: i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; ii) at least every 6 months, at least one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; iii) at least one immune stimulating drug and/or iv) at least one immune stimulating drug and at least one anti-proliferative drug to the subject. In some embodiments of any of the aspects, the reference level is a non-proliferative reference level. In some embodiments of any of the aspects, the bronchoscopy-based procedure further comprises biopsy of the lesions to remove abnormal tissue. 
     In some embodiments, if the subject is determined not to have a decreased level of expression of at least one module 9 gene as compared to a reference level and/or not to have an increased level of expression of at least one module 10 gene as compared to a reference level, the subject i) is not administered an immune stimulating drug, ii) is not administered both an immune stimulating drug and an anti-proliferative drug, iii) is administered a bronchoscopy-based procedure and/or a chest CT scan no more frequently than every 6 months (e.g., no more frequently than every 6, 7, 8, 9, 10, 11, or 12 months), and/or iv) is not administered a bronchoscopy-based procedure to biopsy lesions to remove abnormal tissue. 
     Module 9 genes are provided in Table 13. The at least one module 9 gene can be any one or more of the module 9 genes listed in Table 13. Module 9 genes are provided in Table 16. The at least one module 9 gene can be any one or more of the module 9 genes listed in Table 16. 
     In some embodiments of any of the aspects, the level of expression of two or more module 9 gene is determined. In some embodiments of any of the aspects, the level of expression of each module 9 gene of Table 13 is determined. In some embodiments of any of the aspects, the level of expression of each module 9 gene of Table 16 is determined. 
     In some embodiments of any of the aspects, the at least one module 9 gene comprises or is EPSTI1; UBE2L6; B2M and/or TAP1. In some embodiments of any of the aspects, the at least one module 9 gene comprises or is EPSTI1; UBE2L6; B2M; and TAP1. In some embodiments of any of the aspects, the at least one module 9 gene comprises or is a pairwise combination of any of: 
     EPSTI1 and UBE2L6 
     EPSTI1 and B2M 
     EPSTI1 and TAP1 
     UBE2L6 and B2M 
     UBE2L6 and TAP1 
     B2M and TAP1 
     In some embodiments of any of the aspects, the at least one module 9 gene comprises or is a three-way combination of any of: 
     EPSTI1; UBE2L6; and B2M 
     EPSTI1; UBE2L6; and TAP1 
     EPSTI1; B2M; and TAP1 
     TAP1; UBE2L6; and B2M 
     Module 10 genes are provided in Table 13. The at least one module 10 gene can be any one or more of the module 9 genes listed in Table 13. In some embodiments of any of the aspects, the level of expression of both module 10 genes is determined. In some embodiments of any of the aspects, the at least one module 10 gene comprises or is CACNB3 or MAPK10. In some embodiments of any of the aspects, the at least one module 10 gene comprises or is CACNB3 and MAPK10. 
     When a subject has an inflammatory bronchial premalignant lesion aggressive and/or anti-inflammatory treatment can be beneficial. Accordingly, in one aspect of any of the embodiments, provided herein is a method of treating bronchial premalignant lesions, the method comprising administering at least one of: i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; ii) at least every 6 months, at least one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or iii) at least one anti-inflammatory drug to a subject determined to have at least one of a) an increased level of expression of at least one module 2 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level. In one aspect of any of the embodiments, provided herein is a method of treating bronchial premalignant lesions, the method comprising determining a subject as to have at least one of a) an increased level of expression of at least one module 2 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level and administering at least one of: i) both a bronchoscopy-based procedure to survey the central airway and a chest CT scan; ii) at least every 6 months, at least one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or iii) at least one anti-inflammatory drug to the subject. In some embodiments of any of the aspects, the reference level is a non-inflammatory reference level. 
     In some embodiments, if the subject is determined not to have at least one of a) an increased level of expression of at least one module 2 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level, the subject is not administered an anti-inflammatory drug and is administered a bronchoscopy-based procedure to survey the central airway and/or a chest CT scan no more frequently than every 6 months (e.g., no more frequently than every 6, 7, 8, 9, 10, 11, or 12 months). In some embodiments, if the subject is determined not to have a) an increased level of expression of at least one module 2 gene as compared to a reference level; and b) a decreased level of expression of at least one module 6 gene as compared to a reference level, the subject is not administered an anti-inflammatory drug and is administered a bronchoscopy-based procedure to survey the central airway and/or a chest CT scan no more frequently than every 6 months (e.g., no more frequently than every 6, 7, 8, 9, 10, 11, or 12 months). 
     Module 2 and 6 genes are provided in Table 13. The at least one module 2 gene and/or module 6 gene can be any one or more of the module 5 and 6 genes listed in Table 13. 
     In some embodiments of any of the aspects, the level of expression of at least one module 2 gene or at least one module 6 gene is determined. In some embodiments of any of the aspects, the level of expression of two or more module 2 genes or two or more module 6 genes is determined. In some embodiments of any of the aspects, the level of expression of each module 2 gene or each module 6 gene of Table 13 is determined. 
     In some embodiments of any of the aspects, the level of expression of at least one module 2 gene and at least one module 6 gene is determined. In some embodiments of any of the aspects, the level of expression of two or more module 2 genes and two or more module 6 genes is determined. In some embodiments of any of the aspects, the level of expression of each module 2 gene and each module 6 gene of Table 13 is determined. 
     In some embodiments of any of the aspects, the at least one module 2 gene comprises or is MSANTD2, CCNL2, or LUC7L. In some embodiments of any of the aspects, the at least one module 2 gene comprises or is MSANTD2 and LUC7L. In some embodiments of any of the aspects, the at least one module 2 gene comprises or is MSANTD2 and CCNL2. In some embodiments of any of the aspects, the at least one module 2 gene comprises or is CCNL2 and LUC7L. In some embodiments of any of the aspects, the at least one module 2 gene comprises or is MSANTD2, CCNL2, and LUC7L. In some embodiments of any of the aspects, the at least one module 6 gene comprises or is NEK11 or IFT88. In some embodiments of any of the aspects, the at least one module 6 gene comprises or is NEK11 and IFT88. 
     The inflammatory subtype is further distinguished by increased expression of module 7, 1 and/or 8 and/or decreased expression of module 4 and/or 5. Accordingly, in some embodiments of any of the aspects, the subject is further determined to have at least one of: i) an increased level of expression of at least one module 7, module 1, and/or or module 8 gene, and ii) a decreased level of expression of at least one module 4 or module 5 gene as compared to a reference level. In some embodiments of any of the aspects, the subject is further determined to have at least one of: i) an increased level of expression of at least one module 7, module 1, and/or or module 8 gene, and ii) a decreased level of expression of at least one module 4 or module 5 gene as compared to a reference level. In some embodiments of any of the aspects, the reference level is a non-inflammatory reference level. 
     Module 7, 1, 8, 4 and 5 genes are provided in Table 13. The at least one module 7, 1, 8, 4, and/or 5 gene can be any one or more of the module 7, 1, 8, 4, and/or 5 genes listed in Table 13. In some embodiments of any of the aspects, the level of expression of each module 7, 1, 8, 4 and/or 5 gene of Table 13 is determined. In some embodiments of any of the aspects, the level of expression of each module 7, 1, 8, 4 and 5 gene of Table 13 is determined. 
     In some embodiments of any of the aspects, the at least one module 4 gene comprises or is COX6A1 or COX7A2. In some embodiments of any of the aspects, the at least one module 4 gene comprises or is COX6A1 and COX7A2. In some embodiments of any of the aspects, the at least one module 7 gene comprises or is RPL26 or RPL23. In some embodiments of any of the aspects, the at least one module 7 gene comprises or is RPL26 and RPL23. In some embodiments of any of the aspects, the at least one module 5 gene comprises or is RACGAP1 or TPX2. In some embodiments of any of the aspects, the at least one module 5 gene comprises or is RACGAP1 and TPX2. In some embodiments of any of the aspects, the at least one module 1 gene comprises or is KIRREL; PHLDB1; or MARVELD1. In some embodiments of any of the aspects, the at least one module 1 gene comprises or is PHLDB1 and MARVELD1. In some embodiments of any of the aspects, the at least one module 1 gene comprises or is KIRREL and PHLDB1. In some embodiments of any of the aspects, the at least one module 1 gene comprises or is KIRREL and MARVELD1. In some embodiments of any of the aspects, the at least one module 1 gene comprises or is KIRREL; PHLDB1; and MARVELD1. In some embodiments of any of the aspects, the at least one module 8 gene comprises or is DCO2; CD53; or LAPTM. In some embodiments of any of the aspects, the at least one module 8 gene comprises or is CD53 and LAPTM. In some embodiments of any of the aspects, the at least one module 8 gene comprises or is DCO2 and CD53. In some embodiments of any of the aspects, the at least one module 8 gene comprises or is DCO2 and LAPTM. In some embodiments of any of the aspects, the at least one module 8 gene comprises or is DCO2; CD53; and LAPTM. 
     In some embodiments of any of the aspects, the level of expression of each of the genes of Table 15 is determined. In some embodiments of any of the aspects, the level of expression of each of the genes of Table 15 in a bronchial brushing sample is determined. 
     In some embodiments of any of the aspects, the level of expression of each of the genes of Table 14 is determined. In some embodiments of any of the aspects, the level of expression of each of the genes of Table 14 in a bronchial brushing sample is determined. 
     In some embodiments of any of the aspects, the methods described herein can further comprise determining the level of expression of any of the following genes: SOX2, NFE2L2, PIK3CA (which are squamous cancer marker genes), KRT5, MUC5AC, TUB1A1, SCGB1A1, and FOXK1 (which are epithelial marker genes). 
     As described herein, levels of gene expression can be modulated (e.g., increased or decreased) in subjects with premalignant lesions of different subtypes. 
     In some embodiments of any of the aspects, the method comprises administering a treatment described herein to a subject previously determined to have an expression level(s) as described herein. In some embodiments of any of the aspects, described herein is a method of treating bronchial premalignant lesions in a subject in need thereof, the method comprising: a) first determining the level of expression of the at least one gene in a sample obtained from a subject; and b) then administering a treatment as described herein to the subject if the level of expression of modulated relative to a reference in the manner described herein. In one aspect of any of the embodiments, described herein is a method of treating bronchial premalignant lesions in a subject in need thereof, the method comprising: a) determining if the subject has a modulation of a level of expression as described herein and b) instructing or directing that the subject be administered the appropriate treatment described herein for the particular modulation of expression which has been determined. 
     In some embodiments of any of the aspects, the step of determining if the subject has modulation of an expression level can comprise i) obtaining or having obtained a sample from the subject and ii) performing or having performed an assay on the sample obtained from the subject to determine/measure the level of expression in the subject. In some embodiments of any of the aspects, the step of determining if the subject has a modulation of a level of expression can comprise performing or having performed an assay on a sample obtained from the subject to determine/measure the level of expression in the subject. In some embodiments of any of the aspects, the step of determining if the subject has a modulation of a level of expression can comprise ordering or requesting an assay on a sample obtained from the subject to determine/measure the level of expression in the subject. In some embodiments of any of the aspects, the step of determining if the subject has a modulation of a level of expression can comprise receiving the results of an assay on a sample obtained from the subject to determine/measure the level of expression in the subject. In some embodiments of any of the aspects, the step of determining if the subject has a modulation of a level of expression can comprise receiving a report, results, or other means of identifying the subject as a subject with a modulation of a level of expression. 
     In some embodiments of any of the aspects, the step of instructing or directing that the subject be administered a particular treatment can comprise providing a report of the assay results. In some embodiments of any of the aspects, the step of instructing or directing that the subject be administered a particular treatment can comprise providing a report of the assay results and/or treatment recommendations in view of the assay results. 
     In some embodiments of any of the aspects, measurement of the level of a target and/or detection of the level or presence of a target, e.g. of an expression product (nucleic acid or polypeptide of one of the genes described herein) or a mutation can comprise a transformation. As used herein, the term “transforming” or “transformation” refers to changing an object or a substance, e.g., biological sample, nucleic acid or protein, into another substance. The transformation can be physical, biological or chemical. Exemplary physical transformation includes, but is not limited to, pre-treatment of a biological sample, e.g., from whole blood to blood serum by differential centrifugation. A biological/chemical transformation can involve the action of at least one enzyme and/or a chemical reagent in a reaction. For example, a DNA sample can be digested into fragments by one or more restriction enzymes, or an exogenous molecule can be attached to a fragmented DNA sample with a ligase. In some embodiments of any of the aspects, a DNA sample can undergo enzymatic replication, e.g., by polymerase chain reaction (PCR). 
     Transformation, measurement, and/or detection of a target molecule, e.g. a mRNA or polypeptide can comprise contacting a sample obtained from a subject with a reagent (e.g. a detection reagent) which is specific for the target, e.g., a target-specific reagent. In some embodiments of any of the aspects, the target-specific reagent is detectably labeled. In some embodiments of any of the aspects, the target-specific reagent is capable of generating a detectable signal. In some embodiments of any of the aspects, the target-specific reagent generates a detectable signal when the target molecule is present. 
     Methods to measure gene expression products are known to a skilled artisan. Such methods to measure gene expression products, e.g., protein level, include ELISA (enzyme linked immunosorbent assay), western blot, immunoprecipitation, and immunofluorescence using detection reagents such as an antibody or protein binding agents. Alternatively, a peptide can be detected in a subject by introducing into a subject a labeled anti-peptide antibody and other types of detection agent. For example, the antibody can be labeled with a detectable marker whose presence and location in the subject is detected by standard imaging techniques. 
     For example, antibodies for the various targets described herein are commercially available and can be used for the purposes of the invention to measure protein expression levels. Alternatively, since the amino acid sequences for the targets described herein are known and publically available at the NCBI website, one of skill in the art can raise their own antibodies against these polypeptides of interest for the purpose of the methods described herein. 
     The amino acid sequences of the polypeptides described herein have been assigned NCBI and ENSBL accession numbers for different species such as human, mouse and rat. The sequences for any of the genes described herein can be readily retrieved from either database by one of ordinary skill in the art. In some embodiments of any of the aspects, the sequence of a gene, transcript, or polypeptide described herein is the sequence available in the NCBI or ENSMBL database as of the filing date of this application. 
     In some embodiments of any of the aspects, immunohistochemistry (“IHC”) and immunocytochemistry (“ICC”) techniques can be used. IHC is the application of immunochemistry to tissue sections, whereas ICC is the application of immunochemistry to cells or tissue imprints after they have undergone specific cytological preparations such as, for example, liquid-based preparations. Immunochemistry is a family of techniques based on the use of an antibody, wherein the antibodies are used to specifically target molecules inside or on the surface of cells. The antibody typically contains a marker that will undergo a biochemical reaction, and thereby experience a change of color, upon encountering the targeted molecules. In some instances, signal amplification can be integrated into the particular protocol, wherein a secondary antibody, that includes the marker stain or marker signal, follows the application of a primary specific antibody. 
     In some embodiments of any of the aspects, the assay can be a Western blot analysis. Alternatively, proteins can be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well known in the art and typically involves iso-electric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. These methods also require a considerable amount of cellular material. The analysis of 2D SDS-PAGE gels can be performed by determining the intensity of protein spots on the gel, or can be performed using immune detection. In other embodiments, protein samples are analyzed by mass spectroscopy. 
     Immunological tests can be used with the methods and assays described herein and include, for example, competitive and non-competitive assay systems using techniques such as Western blots, radioimmunoassay (RIA), ELISA (enzyme linked immunosorbent assay), “sandwich” immunoassays, immunoprecipitation assays, immunodiffusion assays, agglutination assays, e.g. latex agglutination, complement-fixation assays, immunoradiometric assays, fluorescent immunoassays, e.g. FIA (fluorescence-linked immunoassay), chemiluminescence immunoassays (CLIA), electrochemiluminescence immunoassay (ECLIA, counting immunoassay (CIA), lateral flow tests or immunoassay (LFIA), magnetic immunoassay (MIA), and protein A immunoassays. Methods for performing such assays are known in the art, provided an appropriate antibody reagent is available. In some embodiments of any of the aspects, the immunoassay can be a quantitative or a semi-quantitative immunoassay. 
     An immunoassay is a biochemical test that measures the concentration of a substance in a biological sample, typically a fluid sample such as blood or serum, using the interaction of an antibody or antibodies to its antigen. The assay takes advantage of the highly specific binding of an antibody with its antigen. For the methods and assays described herein, specific binding of the target polypeptides with respective proteins or protein fragments, or an isolated peptide, or a fusion protein described herein occurs in the immunoassay to form a target protein/peptide complex. The complex is then detected by a variety of methods known in the art. An immunoassay also often involves the use of a detection antibody. 
     Enzyme-linked immunosorbent assay, also called ELISA, enzyme immunoassay or EIA, is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample. The ELISA has been used as a diagnostic tool in medicine and plant pathology, as well as a quality control check in various industries. 
     In one embodiment, an ELISA involving at least one antibody with specificity for the particular desired antigen (e.g., any of the targets as described herein) can also be performed. A known amount of sample and/or antigen is immobilized on a solid support (usually a polystyrene micro titer plate). Immobilization can be either non-specific (e.g., by adsorption to the surface) or specific (e.g. where another antibody immobilized on the surface is used to capture antigen or a primary antibody). After the antigen is immobilized, the detection antibody is added, forming a complex with the antigen. The detection antibody can be covalently linked to an enzyme, or can itself be detected by a secondary antibody which is linked to an enzyme through bio-conjugation. Between each step the plate is typically washed with a mild detergent solution to remove any proteins or antibodies that are not specifically bound. After the final wash step the plate is developed by adding an enzymatic substrate to produce a visible signal, which indicates the quantity of antigen in the sample. Older ELISAs utilize chromogenic substrates, though newer assays employ fluorogenic substrates with much higher sensitivity. 
     In another embodiment, a competitive ELISA is used. Purified antibodies that are directed against a target polypeptide or fragment thereof are coated on the solid phase of multi-well plate, i.e., conjugated to a solid surface. A second batch of purified antibodies that are not conjugated on any solid support is also needed. These non-conjugated purified antibodies are labeled for detection purposes, for example, labeled with horseradish peroxidase to produce a detectable signal. A sample (e.g., a blood sample) from a subject is mixed with a known amount of desired antigen (e.g., a known volume or concentration of a sample comprising a target polypeptide) together with the horseradish peroxidase labeled antibodies and the mixture is then are added to coated wells to form competitive combination. After incubation, if the polypeptide level is high in the sample, a complex of labeled antibody reagent-antigen will form. This complex is free in solution and can be washed away. Washing the wells will remove the complex. Then the wells are incubated with TMB (3, 3′, 5, 5′-tetramethylbenzidene) color development substrate for localization of horseradish peroxidase-conjugated antibodies in the wells. There will be no color change or little color change if the target polypeptide level is high in the sample. If there is little or no target polypeptide present in the sample, a different complex in formed, the complex of solid support bound antibody reagents-target polypeptide. This complex is immobilized on the plate and is not washed away in the wash step. Subsequent incubation with TMB will produce significant color change. Such a competitive ELSA test is specific, sensitive, reproducible and easy to operate. 
     There are other different forms of ELISA, which are well known to those skilled in the art. The standard techniques known in the art for ELISA are described in “Methods in Immunodiagnosis”, 2nd Edition, Rose and Bigazzi, eds. John Wiley &amp; Sons, 1980; and Oellerich, M. 1984, J. Clin. Chem. Clin. Biochem. 22:895-904. These references are hereby incorporated by reference in their entirety. 
     In one embodiment, the levels of a polypeptide in a sample can be detected by a lateral flow immunoassay test (LFIA), also known as the immunochromatographic assay, or strip test. LFIAs are a simple device intended to detect the presence (or absence) of antigen, e.g. a polypeptide, in a fluid sample. There are currently many LFIA tests used for medical diagnostics, either for home testing, point of care testing, or laboratory use. LFIA tests are a form of immunoassay in which the test sample flows along a solid substrate via capillary action. After the sample is applied to the test strip it encounters a colored reagent (generally comprising antibody specific for the test target antigen) bound to microparticles which mixes with the sample and transits the substrate encountering lines or zones which have been pretreated with another antibody or antigen. Depending upon the level of target polypeptides present in the sample the colored reagent can be captured and become bound at the test line or zone. LFIAs are essentially immunoassays adapted to operate along a single axis to suit the test strip format or a dipstick format. Strip tests are extremely versatile and can be easily modified by one skilled in the art for detecting an enormous range of antigens from fluid samples such as urine, blood, water, and/or homogenized tissue samples etc. Strip tests are also known as dip stick tests, the name bearing from the literal action of “dipping” the test strip into a fluid sample to be tested. LFIA strip tests are easy to use, require minimum training and can easily be included as components of point-of-care test (POCT) diagnostics to be use on site in the field. LFIA tests can be operated as either competitive or sandwich assays. Sandwich LFIAs are similar to sandwich ELISA. The sample first encounters colored particles which are labeled with antibodies raised to the target antigen. The test line will also contain antibodies to the same target, although it may bind to a different epitope on the antigen. The test line will show as a colored band in positive samples. In some embodiments of any of the aspects, the lateral flow immunoassay can be a double antibody sandwich assay, a competitive assay, a quantitative assay or variations thereof. Competitive LFIAs are similar to competitive ELISA. The sample first encounters colored particles which are labeled with the target antigen or an analogue. The test line contains antibodies to the target/its analogue. Unlabelled antigen in the sample will block the binding sites on the antibodies preventing uptake of the colored particles. The test line will show as a colored band in negative samples. There are a number of variations on lateral flow technology. It is also possible to apply multiple capture zones to create a multiplex test. 
     The use of “dip sticks” or LFIA test strips and other solid supports have been described in the art in the context of an immunoassay for a number of antigen biomarkers. U.S. Pat. Nos. 4,943,522; 6,485,982; 6,187,598; 5,770,460; 5,622,871; 6,565,808, U.S. patent application Ser. No. 10/278,676; U.S. Ser. No. 09/579,673 and U.S. Ser. No. 10/717,082, which are incorporated herein by reference in their entirety, are non-limiting examples of such lateral flow test devices. Examples of patents that describe the use of “dip stick” technology to detect soluble antigens via immunochemical assays include, but are not limited to U.S. Pat. Nos. 4,444,880; 4,305,924; and 4,135,884; which are incorporated by reference herein in their entireties. The apparatuses and methods of these three patents broadly describe a first component fixed to a solid surface on a “dip stick” which is exposed to a solution containing a soluble antigen that binds to the component fixed upon the “dip stick,” prior to detection of the component-antigen complex upon the stick. It is within the skill of one in the art to modify the teachings of this “dip stick” technology for the detection of polypeptides using antibody reagents as described herein. 
     Other techniques can be used to detect the level of a polypeptide in a sample. One such technique is the dot blot, an adaptation of Western blotting (Towbin et at., Proc. Nat. Acad. Sci. 76:4350 (1979)). In a Western blot, the polypeptide or fragment thereof can be dissociated with detergents and heat, and separated on an SDS-PAGE gel before being transferred to a solid support, such as a nitrocellulose or PVDF membrane. The membrane is incubated with an antibody reagent specific for the target polypeptide or a fragment thereof. The membrane is then washed to remove unbound proteins and proteins with non-specific binding. Detectably labeled enzyme-linked secondary or detection antibodies can then be used to detect and assess the amount of polypeptide in the sample tested. A dot blot immobilizes a protein sample on a defined region of a support, which is then probed with antibody and labelled secondary antibody as in Western blotting. The intensity of the signal from the detectable label in either format corresponds to the amount of enzyme present, and therefore the amount of polypeptide. Levels can be quantified, for example by densitometry. 
     In some embodiments of any of the aspects, the level of a target can be measured, by way of non-limiting example, by Western blot; immunoprecipitation; enzyme-linked immunosorbent assay (ELISA); radioimmunological assay (RIA); sandwich assay; fluorescence in situ hybridization (FISH); immunohistological staining; radioimmunometric assay; immunofluoresence assay; mass spectroscopy and/or immunoelectrophoresis assay. 
     In certain embodiments, the gene expression products as described herein can be instead determined by determining the level of messenger RNA (mRNA) expression of the genes described herein. Such molecules can be isolated, derived, or amplified from a biological sample, such as a blood sample. Techniques for the detection of mRNA expression is known by persons skilled in the art, and can include but not limited to, PCR procedures, RT-PCR, quantitative RT-PCR Northern blot analysis, differential gene expression, RNAse protection assay, microarray based analysis, next-generation sequencing; hybridization methods, etc. 
     In general, the PCR procedure describes a method of gene amplification which is comprised of (i) sequence-specific hybridization of primers to specific genes or sequences within a nucleic acid sample or library, (ii) subsequent amplification involving multiple rounds of annealing, elongation, and denaturation using a thermostable DNA polymerase, and (iii) screening the PCR products for a band of the correct size. The primers used are oligonucleotides of sufficient length and appropriate sequence to provide initiation of polymerization, i.e. each primer is specifically designed to be complementary to a strand of the genomic locus to be amplified. In an alternative embodiment, mRNA level of gene expression products described herein can be determined by reverse-transcription (RT) PCR and by quantitative RT-PCR (QRT-PCR) or real-time PCR methods. Methods of RT-PCR and QRT-PCR are well known in the art. 
     In some embodiments of any of the aspects, the level of an mRNA can be measured by a quantitative sequencing technology, e.g. a quantitative next-generation sequence technology. Methods of sequencing a nucleic acid sequence are well known in the art. Briefly, a sample obtained from a subject can be contacted with one or more primers which specifically hybridize to a single-strand nucleic acid sequence flanking the target gene sequence and a complementary strand is synthesized. In some next-generation technologies, an adaptor (double or single-stranded) is ligated to nucleic acid molecules in the sample and synthesis proceeds from the adaptor or adaptor compatible primers. In some third-generation technologies, the sequence can be determined, e.g. by determining the location and pattern of the hybridization of probes, or measuring one or more characteristics of a single molecule as it passes through a sensor (e.g. the modulation of an electrical field as a nucleic acid molecule passes through a nanopore). Exemplary methods of sequencing include, but are not limited to, Sanger sequencing, dideoxy chain termination, high-throughput sequencing, next generation sequencing, 454 sequencing, SOLiD sequencing, polony sequencing, Illumina sequencing, Ion Torrent sequencing, sequencing by hybridization, nanopore sequencing, Helioscope sequencing, single molecule real time sequencing, RNAP sequencing, and the like. Methods and protocols for performing these sequencing methods are known in the art, see, e.g. “Next Generation Genome Sequencing” Ed. Michal Janitz, Wiley-VCH; “High-Throughput Next Generation Sequencing” Eds. Kwon and Ricke, Humanna Press, 2011; and Sambrook et al., Molecular Cloning: A Laboratory Manual (4 ed.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., USA (2012); which are incorporated by reference herein in their entireties. 
     The nucleic acid sequences of the genes described herein have been assigned NCBI and ENSBL accession numbers for different species such as human, mouse and rat. The sequences for any of the genes described herein can be readily retrieved from either database by one of ordinary skill in the art. In some embodiments of any of the aspects, the sequence of a gene, transcript, or polypeptide described herein is the sequence available in the NCBI or ENSMBL database as of the filing date of this application. Accordingly, a skilled artisan can design an appropriate primer based on the known sequence for determining the mRNA level of the respective gene. 
     Nucleic acid and ribonucleic acid (RNA) molecules can be isolated from a particular biological sample using any of a number of procedures, which are well-known in the art, the particular isolation procedure chosen being appropriate for the particular biological sample. For example, freeze-thaw and alkaline lysis procedures can be useful for obtaining nucleic acid molecules from solid materials; heat and alkaline lysis procedures can be useful for obtaining nucleic acid molecules from urine; and proteinase K extraction can be used to obtain nucleic acid from blood (Roiff, A et al. PCR: Clinical Diagnostics and Research, Springer (1994)). 
     In some embodiments of any of the aspects, one or more of the reagents (e.g. an antibody reagent and/or nucleic acid probe) described herein can comprise a detectable label and/or comprise the ability to generate a detectable signal (e.g. by catalyzing reaction converting a compound to a detectable product). Detectable labels can comprise, for example, a light-absorbing dye, a fluorescent dye, or a radioactive label. Detectable labels, methods of detecting them, and methods of incorporating them into reagents (e.g. antibodies and nucleic acid probes) are well known in the art. 
     In some embodiments of any of the aspects, detectable labels can include labels that can be detected by spectroscopic, photochemical, biochemical, immunochemical, electromagnetic, radiochemical, or chemical means, such as fluorescence, chemifluorescence, or chemiluminescence, or any other appropriate means. The detectable labels used in the methods described herein can be primary labels (where the label comprises a moiety that is directly detectable or that produces a directly detectable moiety) or secondary labels (where the detectable label binds to another moiety to produce a detectable signal, e.g., as is common in immunological labeling using secondary and tertiary antibodies). The detectable label can be linked by covalent or non-covalent means to the reagent. Alternatively, a detectable label can be linked such as by directly labeling a molecule that achieves binding to the reagent via a ligand-receptor binding pair arrangement or other such specific recognition molecules. Detectable labels can include, but are not limited to radioisotopes, bioluminescent compounds, chromophores, antibodies, chemiluminescent compounds, fluorescent compounds, metal chelates, and enzymes. 
     In other embodiments, the detection reagent is label with a fluorescent compound. When the fluorescently labeled reagent is exposed to light of the proper wavelength, its presence can then be detected due to fluorescence. In some embodiments of any of the aspects, a detectable label can be a fluorescent dye molecule, or fluorophore including, but not limited to fluorescein, phycoerythrin, phycocyanin, o-phthaldehyde, fluorescamine, Cy3™, Cy5™, allophycocyanine, Texas Red, peridenin chlorophyll, cyanine, tandem conjugates such as phycoerythrin-Cy5™, green fluorescent protein, rhodamine, fluorescein isothiocyanate (FITC) and Oregon Green™, rhodamine and derivatives (e.g., Texas red and tetrarhodimine isothiocynate (TRITC)), biotin, phycoerythrin, AMCA, CyDyes™, 6-carboxyfhiorescein (commonly known by the abbreviations FAM and F), 6-carboxy-2′,4′,7′,4,7-hexachlorofiuorescein (HEX), 6-carboxy-4′,5′-dichloro-2′,7′-dimethoxyfluorescein (JOE or J), N,N,N′,N′-tetramethyl-6carboxyrhodamine (TAMRA or T), 6-carboxy-X-rhodamine (ROX or R), 5-carboxyrhodamine-6G (R6G5 or G5), 6-carboxyrhodamine-6G (R6G6 or G6), and rhodamine 110; cyanine dyes, e.g. Cy3, Cy5 and Cy7 dyes; coumarins, e.g umbelliferone; benzimide dyes, e.g. Hoechst 33258; phenanthridine dyes, e.g. Texas Red; ethidium dyes; acridine dyes; carbazole dyes; phenoxazine dyes; porphyrin dyes; polymethine dyes, e.g. cyanine dyes such as Cy3, Cy5, etc; BODIPY dyes and quinoline dyes. In some embodiments of any of the aspects, a detectable label can be a radiolabel including, but not limited to  3 H,  125 I,  35 S,  14 C,  32 P, and  33 P. In some embodiments of any of the aspects, a detectable label can be an enzyme including, but not limited to horseradish peroxidase and alkaline phosphatase. An enzymatic label can produce, for example, a chemiluminescent signal, a color signal, or a fluorescent signal. Enzymes contemplated for use to detectably label an antibody reagent include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-V-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-VI-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. In some embodiments of any of the aspects, a detectable label is a chemiluminescent label, including, but not limited to lucigenin, luminol, luciferin, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester. In some embodiments of any of the aspects, a detectable label can be a spectral colorimetric label including, but not limited to colloidal gold or colored glass or plastic (e.g., polystyrene, polypropylene, and latex) beads. 
     In some embodiments of any of the aspects, detection reagents can also be labeled with a detectable tag, such as c-Myc, HA, VSV-G, HSV, FLAG, V5, HIS, or biotin. Other detection systems can also be used, for example, a biotin-streptavidin system. In this system, the antibodies immunoreactive (i. e. specific for) with the biomarker of interest is biotinylated. Quantity of biotinylated antibody bound to the biomarker is determined using a streptavidin-peroxidase conjugate and a chromogenic substrate. Such streptavidin peroxidase detection kits are commercially available, e. g. from DAKO; Carpinteria, CA. A reagent can also be detectably labeled using fluorescence emitting metals such as  152 Eu, or others of the lanthanide series. These metals can be attached to the reagent using such metal chelating groups as diethylenetriaminepentaacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA). 
     In some embodiments of any of the aspects, the level of expression is the level in a sample obtained from a subject. The term “sample” or “test sample” as used herein denotes a sample taken or isolated from a biological organism, e.g., a blood or tissue sample from a subject. In some embodiments of any of the aspects, the present invention encompasses several examples of a biological sample. In some embodiments of any of the aspects, the biological sample is cells, or tissue, or peripheral blood, or bodily fluid. Exemplary biological samples include, but are not limited to, a biopsy, a tumor sample, biofluid sample; blood; serum; plasma; urine; sperm; mucus; tissue biopsy; organ biopsy; synovial fluid; bile fluid; cerebrospinal fluid; mucosal secretion; effusion; sweat; saliva; and/or tissue sample etc. The term also includes a mixture of the above-mentioned samples. The term “test sample” also includes untreated or pretreated (or pre-processed) biological samples. In some embodiments of any of the aspects, a test sample can comprise cells from a subject. In some embodiments of any of the aspects, the sample obtained from a subject can be a biopsy sample. In some embodiments of any of the aspects, the sample obtained from a subject can be a blood or serum sample. 
     In some embodiments of any of the aspects, the sample is an endobronchial biopsy, bronchial brushing sample, bronchial biopsy, endobronchial brushing sample, large airway biopsy, large airway brushing sample, nasal epithelial cells, sputum, and/or blood obtained from the subject. In some embodiments of any of the aspects, the sample is a bronchial brushing obtained from the right or left mainstem bronchus. The test sample can be obtained by removing a sample from a subject, but can also be accomplished by using a previously isolated sample (e.g. isolated at a prior timepoint and isolated by the same or another person). 
     In some embodiments of any of the aspects, the test sample can be an untreated test sample. As used herein, the phrase “untreated test sample” refers to a test sample that has not had any prior sample pre-treatment except for dilution and/or suspension in a solution. Exemplary methods for treating a test sample include, but are not limited to, centrifugation, filtration, sonication, homogenization, heating, freezing and thawing, and combinations thereof. In some embodiments of any of the aspects, the test sample can be a frozen test sample, e.g., a frozen tissue. The frozen sample can be thawed before employing methods, assays and systems described herein. After thawing, a frozen sample can be centrifuged before being subjected to methods, assays and systems described herein. In some embodiments of any of the aspects, the test sample is a clarified test sample, for example, by centrifugation and collection of a supernatant comprising the clarified test sample. In some embodiments of any of the aspects, a test sample can be a pre-processed test sample, for example, supernatant or filtrate resulting from a treatment selected from the group consisting of centrifugation, filtration, thawing, purification, and any combinations thereof. In some embodiments of any of the aspects, the test sample can be treated with a chemical and/or biological reagent. Chemical and/or biological reagents can be employed to protect and/or maintain the stability of the sample, including biomolecules (e.g., nucleic acid and protein) therein, during processing. One exemplary reagent is a protease inhibitor, which is generally used to protect or maintain the stability of protein during processing. The skilled artisan is well aware of methods and processes appropriate for pre-processing of biological samples required for determination of the level of an expression product as described herein. 
     In some embodiments of any of the aspects, the methods, assays, and systems described herein can further comprise a step of obtaining or having obtained a test sample from a subject. In some embodiments of any of the aspects, the subject can be a human subject. In some embodiments of any of the aspects, the subject can be a subject in need of treatment for (e.g. having or diagnosed as having) premalignant lesions or a subject at risk of or at increased risk of developing bronchial premalignant lesions as described elsewhere herein. 
     In some embodiments of any of the aspects, the biopsy or brushing sample comprises morphologically-normal tissues or cells, e.g., the tissues or cells are not from a lesion and display normal morphology for their in vivo location. In some embodiments of any of the aspects, the biopsy or brushing sample consists essentially of morphologically-normal tissues or cells. In some embodiments of any of the aspects, the biopsy or brushing sample consists of morphologically-normal tissues or cells. 
     In some embodiments of any of the aspects, the biopsy or brushing sample comprises visually-normal tissues or cells, e.g., the tissues or cells are not from a lesion and to the unaided human eye have a normal appearance for their in vivo location. In some embodiments of any of the aspects, the biopsy or brushing sample consists essentially of visually-normal tissues or cells. In some embodiments of any of the aspects, the biopsy or brushing sample consists of visually-normal tissues or cells. 
     In some embodiments of any of the aspects, the biopsy or brushing sample comprises bronchial premalignant lesion cells. In some embodiments of any of the aspects, the biopsy or brushing sample consists essentially of bronchial premalignant lesion cells. In some embodiments of any of the aspects, the biopsy or brushing sample consists of bronchial premalignant lesion cells. 
     A level which is less than a reference level can be a level which is less by at least about 10%, at least about 20%, at least about 50%, at least about 60%, at least about 80%, at least about 90%, or less relative to the reference level. In some embodiments of any of the aspects, a level which is less than a reference level can be a level which is statistically significantly less than the reference level. 
     A level which is more than a reference level can be a level which is greater by at least about 10%, at least about 20%, at least about 50%, at least about 60%, at least about 80%, at least about 90%, at least about 100%, at least about 200%, at least about 300%, at least about 500% or more than the reference level. In some embodiments of any of the aspects, a level which is more than a reference level can be a level which is statistically significantly greater than the reference level. 
     In some embodiments of any of the aspects, the reference can be a level of the target molecule in a population of subjects who do not have or are not diagnosed as having, and/or do not exhibit signs or symptoms of bronchial premalignant lesions. In some embodiments of any of the aspects, the reference can also be a level of expression of the target molecule in a control sample, a pooled sample of control individuals or a numeric value or range of values based on the same. In some embodiments of any of the aspects, the reference can be the level of a target molecule in a sample obtained from the same subject at an earlier point in time, e.g., the methods described herein can be used to determine if a subject&#39;s sensitivity or response to a given therapy is changing over time or if the subtype of their lesions is changing. 
     In some embodiments of any of the aspects, the level of expression products of no more than 200 other genes is/are determined. In some embodiments of any of the aspects, the level of expression products of no more than 100 other genes is/are determined. In some embodiments of any of the aspects, the level of expression products of no more than 20 other genes is/are determined. In some embodiments of any of the aspects, the level of expression products of no more than 10 other genes is/are determined. 
     In some embodiments of the foregoing aspects, the expression level of a given gene can be normalized relative to the expression level of one or more reference genes or reference proteins. 
     In some embodiments, the reference level can be the level in a sample of similar cell type, sample type, sample processing, and/or obtained from a subject of similar age, sex and other demographic parameters as the sample/subject for which the level of expression is to be determined. In some embodiments, the test sample and control reference sample are of the same type, that is, obtained from the same biological source, and comprising the same composition, e.g. the same number and type of cells. 
     In some embodiments of any of the aspects, the reference level can be a non-proliferative reference level, e.g., the level in a tissue or cell not comprising a proliferative lesion or from a subject who does not have a proliferative lesion. For example, the level can be the level in inflammatory, secretory, or normal-like lesion subtypes or an average or pooling thereof. 
     In some embodiments, the methods described herein relate to treating a subject having or diagnosed as having bronchial premalignant lesions. Subjects having bronchial premalignant lesions can be identified by a physician using current methods of diagnosing bronchial premalignant lesions. Tests that may aid in a diagnosis of, e.g. bronchial premalignant lesions include, but are not limited to, bronchoscopy, autofluorescence bronchoscopy, etc. A family history of bronchial premalignant lesions or exposure to risk factors for bronchial premalignant lesions (e.g. cigarette smoke) can also aid in determining if a subject is likely to have bronchial premalignant lesions or in making a diagnosis of bronchial premalignant lesions. 
     The compositions and methods described herein can be administered to a subject having or diagnosed as having bronchial premalignant lesions. In some embodiments, the methods described herein comprise administering an effective amount of compositions described herein to a subject in order to alleviate a symptom of a bronchial premalignant lesions. As used herein, “alleviating a symptom of a bronchial premalignant lesions” is ameliorating any condition or symptom associated with the bronchial premalignant lesions. As compared with an equivalent untreated control, such reduction is by at least 5%, 10%, 20%, 40%, 50%, 60%, 80%, 90%, 95%, 99% or more as measured by any standard technique. A variety of means for administering the compositions described herein to subjects are known to those of skill in the art. Such methods can include, but are not limited to oral, parenteral, intravenous, intramuscular, subcutaneous, transdermal, airway (aerosol), pulmonary, cutaneous, topical, injection, or intratumoral administration. Administration can be local or systemic. 
     The methods described herein can prevent, delay, or slow the development of lung cancer, e.g., lung squamous cell carcinoma. In some embodiments of any of the aspects, the subject treated according to the present methods is not a subject with lung cancer. In some embodiments of any of the aspects, the subject treated according to the present methods is a subject who does not have lung cancer. In some embodiments of any of the aspects, the subject treated according to the present methods is a subject who does not have and has not had lung cancer. In some embodiments of any of the aspects, the subject treated according to the present methods is at risk of lung cancer. In some embodiments of any of the aspects, the subject is a subject with a bronchial premalignant lesion. 
     In some embodiments of any of the aspects, the subject is a smoker. In some embodiments of any of the aspects, the subject is a former smoker. In some embodiments of any of the aspects, the subject is a non-smoker. 
     The treatments described herein, e.g. an anti-proliferative drug, anti-inflammatory drug, or immune stimulating drug can be administered systemically, by inhalation, and/or topically to any portion of the airways of a subject (including the nose and mouth). In some embodiments of any of the aspects, a treatment described herein, e.g. an anti-proliferative drug, anti-inflammatory drug, or immune stimulating drug can be administered i) systemically and ii) by inhalation or topically to any portion of the airways of a subject (including the nose and mouth) during a bronchoscopy or brushing collection. 
     An anti-proliferative drug is a drug that inhibits cell growth and/or division, e.g., cytostatic agents, wherein that is the primary activity of the compound in the relevant context. Non-limiting examples of anti-proliferative drugs can include CDK inhibitors (e.g. purvalanol-a, palbociclib, ribociclib, abemaciclib, and olomoucine II); HDAC inhibitors (e.g. THM-I-94, vorinostat, givinostat); PARP inhibitors (e.g. AG-14361, olaparib, rucaparib, niraparib, talazoparib, veliparib, pamiparib, CEP 9722, E7016, iniparib, 3-aminobenazmide); JAK inhibitors (e.g. JAK3-inhibitor-VI, ruxolitinib, tofacitinib, oclacitinib, baricitinib, peficitinib, filgotinib, cerdulatinib, gandotinib, lestaurtinib, momelotinib, pacritinib, PF-04965842, upadacitinib, fedratinib, cucurbitacin, CHZ868); JNK inhibitors (e.g. ZG-10, AS-601245, AM-111); MTOR inhibitors (e.g. AZD-8055, PI-103, rapamycin, temsirolimus, everolimus, ridaforolimus, rapalogs, sirolimus); FLT3 inhibitors (e.g. lestaurtinib, TG-101348, gilteritinib, quizartinib, midostaurin, sorafenib, sunitinib); PI3K inhibitors (e.g. GDC-0941, PI-828, wortmannin, LY294002, hibiscone C, idelalisib, copanlisib, duvelisib, alpelisib, taselisib, perifosine, buparlisib, umbralisib, PX-866, dactolisib, CUDC-907, voxtalisib, ME-401, IPI-549, SF1126, PR6530, INK1117, pictilisib, XL147, palmoid 529, GSK1059615, ZSTK474, PWT33597, IC87114, TG100-115, CAL263, RP6503, PI-103, GNE-477, AEZS-136); AKT inhibitors (e.g. A-443644, pyrvinium-pamoate, VQD-002, perifosine, miltefosine, MK-2206, AZD5363, ipataseritib); tyrosine kinase inhibitors (e.g. aminopurvalanol-a, SU-11652, imatinib, gefitinib, erlotinib, sunitinib, adavosertib, lapatinib); protein kinase inhibitors (e.g. HG-5-113-01, adavosertib, afatinib, axitinib, bosuntinib, cetuximab, conbimetinib, crizotinib, cabozantinib, dasatinib, entrectinib, erdafitinib, erlotinib, fostamatinib, gefitinib, ibrutinib, imatinib, lapatinib, lenvatinib, mubritinib, nilotinib, pazopanib, pegaptanib, ruxolitinib, sorafenib, sunitinib, SU6656, vandetanib, vemurafenib); RNA polymerase inhibitor (e.g. dactinomycin, triptolide); topoisomerase inhibitors (e.g. pidorubicine, doxorubicin, campothecins, indenosioquinolines, indotecan, imdimitecan, amsacrine, etoposide, teniposide, ICRF-193, genistein); HSP inhibitors (e.g. HSP90-inhibitor, 17-N-Allylamino-17-demethoxygeldanamycin (17AAG), gamitrinib); DNA protein kinase inhibitors (e.g., PIK-75); focal adhesion kinase inhibitors (e.g. PF-562271, PF573,228, PF-271, NVP-226, Y15, PND-1186, GSK2256098, VS-6062, VS-6063, VS-4718); RNA synthesis inhibitor (daunorubicin); mediator release inhibitor (e.g. ER-27319); and EZH2 inhibitors (DZNep, EPZ005687, EI1, GSK126, UNC1999, EPZ-6438, tazemetostat). Further non-limiting examples of anti-proliferative drugs include Acetylcholine receptor antagonists (e.g., clozapine, quetiapine, atropine, benztropine, biperiden, chlorpheniramine, citalopram, dycyclomine, dimenthydrinate, diphenhydramine, doxepin, doxylamine, glycopyrrolate, glycopyrronium, hyoscyamine, ipratropium, orphenadrine, oxitropium, oxybutynin, promethazine, propantheline bromide, scopolamine, solifenacin, solifenacin, tolterodine, tiotropium, trihexyphenidyl, tropicamide, tubocurarine, mecamylamine, hexamethonium, doxacurium, dextromethorphan, bupriopion); Acetylcholinesterase inhibitors (e.g. Physostigmine, Neostigmine, Pyridostigmine, Ambenonium, Demecarium, Rivastigmine, Phenanthrene derivatives, Galantamine, Alpha-Pinene—noncompetitive reversible, Piperidines, Donepezil, Tacrine, Edrophonium, Huperzine A, Ladostigil, Ungeremine, Lactucopicrin, and Acotiamide); Adenosine receptor antagonists (e.g., theophylline and theobromine); Adrenergic receptor antagonists (e.g., Phentolamine, phenoxybenzamine, Propranolol, Nebivilol, Atenolol, Oxprenolol, Metoprolol, Timolol, Pindolol, Nadolol, Pindolol, Esmolol, Acebutolol, Sotalol, Talinolol, Betaxolol, Labetalol, and Carvedilol); Angiotensin receptor antagonists (e.g., candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan); Apoptosis stimulants (e.g., Asiatic acid, glycodeoxychoic acid); Cyclooxygenase inhibitors (e.g., celecoxib, rofecoxib); Cytokine production inhibitors (e.g., sirolimus, basiliximab, daclizumab); Dehydrogenase inhibitors ((e.g., mycophenolate-mofetil, mycophenolic acid); Dopamine receptor antagonist (e.g., benperidol, chlorpromazine, clopenthixol, droperidol, haloperidol, fluphenazine, flupenthixol, fluspirilene, penfluridol, perazine, perphenazine, pimozide, spiperone, sulpiride, thioridazine, amisulpride, aseanapine, aripriprazole, clozapine, loxapine, nemonapride, olanzapine, quetiapine, paliperidone, remoxipride, risperidone, tiapride, ziprasidone, domperidone, bromopride, metoclopramide, eticlopride, nafadotride, raclopride); EGFR inhibitors (e.g., gefitinib, erlotinib, iapatinib, osimertinib, cetuximab, neratinib, pnaitumumab, vandetanib, necitumumab, dacomitinib); ERK1 and ERK2 phosphorylation inhibitors (e.g., RAF, RAS, or MEK inhibitors); Estrogen receptor agonists (e.g., ethinylestradiol, diethylstilbestrol, phytoestrogens, tamoxifen, clomifene, raloxifene); Glutamate receptor antagonists (e.g., AP5, barbiturates, dextromethorphan, dextrorphan, dizoclipin, ibogaine, ifenprodil, ketamine, kynurenic acid, memantine, perampanel, phencyclidine); Histamine receptor antagonists (e.g., cimetidine, ranitidine, famotidine, nizatidine, roxatidine, lafutidine); Histone lysine methyltransferase inhibitors (EPZ004777, EPZ5676, BIX01294); IKK inhibitors (e.g., curcumin, embelin, auranofine, butein, IMD 0354, IKK 16, SC514, BAY 11-7082, MRT67307, BMS-345541, amlexanox, MLN120B); Ion channel antagonists (e.g., erastin); Leucine rich repeat kinase inhibitors (e.g., MLi-2, PF-06447475, GSK2578215, LRKK2-IN1, HG 10/102/01, CZC-25146); MDM inhibitors (e.g., tenovin-2, idasanutlin, SP141 MI-773, R08994, AMG232, nutlin-3); Monoamine oxidase inhibitors (e.g., hydrazine, isocarboxazid, nialamide, phenelzine, hydracarbazine, tnrylcypromine, befemelane, moclobemide, pirlindole, toloxatone, rasagiline, selegiline, safinamide); nucleophosmin inhibitors (e.g., EAPB0503, NSC348884, Rev37-47 CIGB-300, avrainvillamide, deguelin, EPTG, YTR107); PPAR receptor agonists (e.g. clofibrate, gemfibrozil, ciprofibrate, bezafibrate, fenofibrate, thiazolidinediones, BW501516, aleglitazar, muraglitizar, tesaglitzar); Phosphodiesterase inhibitors (e.g., vinpocetine, ENHA, BAY 60-7550, oxindole, PDP, IBMX, aminophylline, praxanthine, pentoxifylline, theobromine, inamrinone, milrinone, enoximone, anagrelide, cilostazol, pimobendan); SIRT inhibitors (e.g., (s)-2-phentyl-6-chloro, 8-bormo-chroman one, 3′-phenethyloxy-2-anilinobenzamide); sodium channel blockers (e.g., procainamide, quinidine, disopyramide, lidocaine, mexiletine, tocainide, phenytoin, encainide, flecainide, moricizine, propafenone); and Vitamin D receptor agonists (e.g., EB 1089, BXL-01-0029, elocalcitol). In some embodiments, anti-proliferative drugs lacking anti-inflammatory activity in any context described herein can include JAK inhibitors, JNK inhibitors, AKT inhibitors, protein kinase inhibitors, RNA polymerase inhibitors, HSP inhibitors, DNA protein kinase inhibitors, focal adhesion inhibitors, RNA synthesis inhibitors, and mediator release inhibitors. 
     As used herein, the term “anti-inflammatory” refers to a compound capable of reducing or inhibiting inflammation, wherein that is the primary activity of the compound in the relevant context. As used herein, the term “anti-inflammatory drug” or “anti-inflammatory agent” is used to describe any compound (including its analogs, derivatives, prodrugs and pharmaceutically salts) which can be used reduce or inhibit inflammation. Non-limiting examples of anti-inflammatory drugs can include NFkB pathway inhibitors (e.g. 9-methyl-5H-6-thia-4,5-diaza-chrysene-6,6-dioxide, denosumab, disulfiram, olmesartan, dithiocarbamates, anatabine, BAY 11-7082, palmitoylethanolamide, iguartimod); protein synthesis inhibitors (e.g. chloramphenicol); anti-IL1B antibodies (e.g., Canakinumab); glucocorticoid receptor agonists (e.g. dexamethasone, mifepristone,); and TGF beta receptor inhibitors (e.g. LY-364947, GW-755.55, LY-2109761, galunisertib, SB431542, SB-525334). Further non-limiting examples of anti-proliferative drugs include Acetylcholine receptor antagonist; Acetylcholinesterase inhibitors; Adenosine receptor antagonists; Adrenergic receptor antagonists; Angiotensin receptor antagonists; Apoptosis stimulants; Cyclooxygenase inhibitors; Cytokine production inhibitors; Dehydrogenase inhibitors; Dopamine receptor antagonist; EGFR inhibitors; ERK1 and ERK2 phosphorylation inhibitors; Estrogen receptor agonists; Glutamate receptor antagonists; Histamine receptor antagonists; Histone lysine methyltransferase inhibitors; IKK inhibitors; Ion channel antagonists; Leucine rich repeat kinase inhibitors; MDM inhibitors; Monoamine oxidase inhibitors; nucleophosmin inhibitors; PPAR receptor agonists; Phosphodiesterase inhibitors; SIRT inhibitors; sodium channel blockers; and Vitamin D receptor agonists. In some embodiments, anti-inflammatory drugs lacking anti-proliferative activity in any context described herein can include protein synthesis inhibitors and TGF beta receptor inhibitors. 
     It is noted herein that a single compound may exhibit multiple activities, e.g., depending on the context. Non-examples of agents that can exhibit primarily an anti-inflammatory activity and/or an anti-proliferative activity, depending on the context (e.g., the subject or cell being administered/contacted with the agent) can include Acetylcholine receptor antagonist, Acetylcholinesterase inhibitors, Adenosine receptor antagonists, Adrenergic receptor antagonists, Angiotensin receptor antagonists, Apoptosis stimulants, Aurora kinase inhibitors, CDK inhibitors, Cyclooxygenase inhibitors, Cytokine production inhibitors, Dehydrogenase inhibitors, Dopamine receptor antagonist, EGFR inhibitors, ERK1 and ERK2 phosphorylation inhibitors, Estrogen receptor agonists, FLT3 inhibitors, Glucocorticoid receptor agonists, Glutamate receptor antagonists, HDAC inhibitors, Histamine receptor antagonists, Histone lysine methyltransferase inhibitors, HSP inhibitors, IKK inhibitors, Ion channel antagonists, KIT inhibitors, Leucine rich repeat kinase inhibitors, MEK inhibitors, MDM inhibitors, Phosphodiesterase inhibitors, Monoamine oxidase inhibitors, MTOR inhibitors, NFkB pathway inhibitors, nucleophosmin inhibitors, PARP inhibitors, PI3K inhibitors, PPAR receptor agonist, RAF inhibitors, SIRT inhibitors, Sodium channel blockers, Topoisomerase inhibitors, Tyrosine kinase inhibitors, VEGFR inhibitors, and a Vitamin D receptor agonists. 
     An immune-stimulating drug is a drug that increases the activity of the immune system, preferably against cancer or dysplasia cells, wherein that is the primary activity of the compound in the relevant context. As used herein, the term “immune-stimulating drug” or “anti-inflammatory agent” is used to describe any compound (including its analogs, derivatives, prodrugs and pharmaceutically salts) which can be used stimulate the immune system. Non-limiting examples of immune stimulating drugs can include immune-checkpoint inhibitors (e.g. inhibitors against, PD-1, PD-L1, CTLA4, and LAG3); drugs that stimulate interferon signaling (e.g. anti-viral drugs that improve interferon signaling such as Pegintron, Pegasys, referon A, uniferon, multiferon, rebif, avonex, cinnovex, betaseron, actimmune, reiferon, pegetron); DNA synthesis inhibitors (e.g., TAS-102, NC-6004, ganciclovir); CDK inhibitors (e.g. purvalanol-a, palbociclib, ribociclib, abemaciclib, and olomoucine II); ribonucleotide reductase inhibitors (e.g., motexafin, hydroxyurea, fludarabine, cladribine, gemcitabine, tezacitabine, triapine, gallium maltolate, gallium nitrate); dihydrofolate reductase inhibitors (e.g., methotrexate, piritrexam, cycloguanil, JPC-2056); topoisomerase inhibitors (e.g. pidorubicine, doxorubicin, campothecins, indenosioquinolines, indotecan, imdimitecan, amsacrine, etoposide, teniposide, ICRF-193, genistein); FLT3 inhibitors (e.g. lestaurtinib, TG-101348, gilteritinib, quizartinib, midostaurin, sorafenib, sunitinib); IGF-1 inhibitors; MEK inhibitors (e.g., trametinib, cobimetinib, binimetinib, selumetinib, PD-325901, TAK-733); aurora kinase inhibitors (e.g., ZM447439, hesperidin, VX-680); PKC inhibitors (e.g., ruboxistaurin, chelerythrine, miyabenol C, myricitrin, gossypol, verbascoside, BIM-1, bryostate 1, tamoxifen); RAF inhibitors (e.g., vemurafenib, GDC-0879, PLX-4720, sorafenib, dabrafenib, LGX818); PDFGR/KIT inhibitors (e.g., imatinib, sunitinib, sorafenib, pazopanib, nilotinib, motesanib, linifenib); VEGFR inhibitors (e.g., axitinib, cabozantinib, lenvatinib, pazopanib, vandetanib); SRC inhibitors (e.g., KX2-391, bosutinib, saracatinib, PP1, PP2, quercetin, dastabinib); retinoid receptor agonists (e.g., alitretinoin, isoretinoin); HDAC inhibitors (e.g. THM-I-94, vorinostat, givinostat); DNA methyltransferase inhibitors (e.g., azacytidine, decitabine, zeublarine); and EZH2 inhibitors (DZNep, EPZ005687, EI1, GSK126, UNC1999, EPZ-6438, tazemetostat). 
     In some embodiments, immune stimulating drugs lacking anti-proliferative/inflammatory activity in any context described herein can include immune-checkpoint inhibitors (e.g. inhibitors against, PD-1, PD-L1, CTLA4, and LAG3); drugs that stimulate interferon signaling (e.g. anti-viral drugs that improve interferon signaling); DNA synthesis inhibitors; IMDH inhibitors; ribonucleotide reductase inhibitors; dihydrofolate reductase inhibitors; SRC inhibitors; retinoid receptor agonists; HDAC inhibitors; and DNA methyltransferase inhibitors. 
     The term “effective amount” as used herein refers to the amount of a composition needed to alleviate at least one or more symptom of the disease or disorder, and relates to a sufficient amount of pharmacological composition to provide the desired effect. The term “therapeutically effective amount” therefore refers to an amount of the composition that is sufficient to provide a particular therapeutic effect when administered to a typical subject. An effective amount as used herein, in various contexts, would also include an amount sufficient to delay the development of a symptom of the disease, alter the course of a symptom disease (for example but not limited to, slowing the progression of a symptom of the disease), or reverse a symptom of the disease. Thus, it is not generally practicable to specify an exact “effective amount”. However, for any given case, an appropriate “effective amount” can be determined by one of ordinary skill in the art using only routine experimentation. 
     Effective amounts, toxicity, and therapeutic efficacy can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dosage can vary depending upon the dosage form employed and the route of administration utilized. The dose ratio between toxic and therapeutic effects is the therapeutic index and can be expressed as the ratio LD50/ED50. Compositions and methods that exhibit large therapeutic indices are preferred. A therapeutically effective dose can be estimated initially from cell culture assays. Also, a dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the active ingredient, which achieves a half-maximal inhibition of symptoms) as determined in cell culture, or in an appropriate animal model. Levels in plasma can be measured, for example, by high performance liquid chromatography. The effects of any particular dosage can be monitored by a suitable bioassay, e.g., assay for gene expression as described herein, among others. The dosage can be determined by a physician and adjusted, as necessary, to suit observed effects of the treatment. 
     In some embodiments, the technology described herein relates to a pharmaceutical composition comprising a drug as described herein, and optionally a pharmaceutically acceptable carrier. In some embodiments, the active ingredients of the pharmaceutical composition comprise the drug as described herein. In some embodiments, the active ingredients of the pharmaceutical composition consist essentially of the drug as described herein. In some embodiments, the active ingredients of the pharmaceutical composition consist of the drug as described herein. Pharmaceutically acceptable carriers and diluents include saline, aqueous buffer solutions, solvents and/or dispersion media. The use of such carriers and diluents is well known in the art. Some non-limiting examples of materials which can serve as pharmaceutically-acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, microcrystalline cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) lubricating agents, such as magnesium stearate, sodium lauryl sulfate and talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol (PEG); (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer&#39;s solution; (19) ethyl alcohol; (20) pH buffered solutions; (21) polyesters, polycarbonates and/or polyanhydrides; (22) bulking agents, such as polypeptides and amino acids (23) serum component, such as serum albumin, HDL and LDL; (22) C 2 -C 12  alcohols, such as ethanol; and (23) other non-toxic compatible substances employed in pharmaceutical formulations. Wetting agents, coloring agents, release agents, coating agents, sweetening agents, flavoring agents, perfuming agents, preservative and antioxidants can also be present in the formulation. The terms such as “excipient”, “carrier”, “pharmaceutically acceptable carrier” or the like are used interchangeably herein. In some embodiments, the carrier inhibits the degradation of the active agent. 
     In some embodiments, the pharmaceutical composition comprising a drug as described herein can be a parenteral dose form. Since administration of parenteral dosage forms typically bypasses the patient&#39;s natural defenses against contaminants, parenteral dosage forms are preferably sterile or capable of being sterilized prior to administration to a patient. Examples of parenteral dosage forms include, but are not limited to, solutions ready for injection, dry products ready to be dissolved or suspended in a pharmaceutically acceptable vehicle for injection, suspensions ready for injection, and emulsions. In addition, controlled-release parenteral dosage forms can be prepared for administration of a patient, including, but not limited to, DURO S®-type dosage forms and dose-dumping. 
     Suitable vehicles that can be used to provide parenteral dosage forms of a drug as disclosed within are well known to those skilled in the art. Examples include, without limitation: sterile water; water for injection USP; saline solution; glucose solution; aqueous vehicles such as but not limited to, sodium chloride injection, Ringer&#39;s injection, dextrose Injection, dextrose and sodium chloride injection, and lactated Ringer&#39;s injection; water-miscible vehicles such as, but not limited to, ethyl alcohol, polyethylene glycol, and propylene glycol; and non-aqueous vehicles such as, but not limited to, corn oil, cottonseed oil, peanut oil, sesame oil, ethyl oleate, isopropyl myristate, and benzyl benzoate. Compounds that alter or modify the solubility of a pharmaceutically acceptable salt of the drug as disclosed herein can also be incorporated into the parenteral dosage forms of the disclosure, including conventional and controlled-release parenteral dosage forms. 
     Pharmaceutical compositions comprising a drug can also be formulated to be suitable for oral administration, for example as discrete dosage forms, such as, but not limited to, tablets (including without limitation scored or coated tablets), pills, caplets, capsules, chewable tablets, powder packets, cachets, troches, wafers, aerosol sprays, or liquids, such as but not limited to, syrups, elixirs, solutions or suspensions in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion, or a water-in-oil emulsion. Such compositions contain a predetermined amount of the pharmaceutically acceptable salt of the disclosed compounds, and may be prepared by methods of pharmacy well known to those skilled in the art. See generally, Remington: The Science and Practice of Pharmacy, 21st Ed., Lippincott, Williams, and Wilkins, Philadelphia Pa. (2005). 
     Conventional dosage forms generally provide rapid or immediate drug release from the formulation. Depending on the pharmacology and pharmacokinetics of the drug, use of conventional dosage forms can lead to wide fluctuations in the concentrations of the drug in a patient&#39;s blood and other tissues. These fluctuations can impact a number of parameters, such as dose frequency, onset of action, duration of efficacy, maintenance of therapeutic blood levels, toxicity, side effects, and the like. Advantageously, controlled-release formulations can be used to control a drug&#39;s onset of action, duration of action, plasma levels within the therapeutic window, and peak blood levels. In particular, controlled- or extended-release dosage forms or formulations can be used to ensure that the maximum effectiveness of a drug is achieved while minimizing potential adverse effects and safety concerns, which can occur both from under-dosing a drug (i.e., going below the minimum therapeutic levels) as well as exceeding the toxicity level for the drug. In some embodiments, the drug can be administered in a sustained release formulation. 
     Controlled-release pharmaceutical products have a common goal of improving drug therapy over that achieved by their non-controlled release counterparts. Ideally, the use of an optimally designed controlled-release preparation in medical treatment is characterized by a minimum of drug substance being employed to cure or control the condition in a minimum amount of time. Advantages of controlled-release formulations include: 1) extended activity of the drug; 2) reduced dosage frequency; 3) increased patient compliance; 4) usage of less total drug; 5) reduction in local or systemic side effects; 6) minimization of drug accumulation; 7) reduction in blood level fluctuations; 8) improvement in efficacy of treatment; 9) reduction of potentiation or loss of drug activity; and 10) improvement in speed of control of diseases or conditions. Kim, Cherng-ju, Controlled Release Dosage Form Design, 2 (Technomic Publishing, Lancaster, Pa.: 2000). 
     Most controlled-release formulations are designed to initially release an amount of drug (active ingredient) that promptly produces the desired therapeutic effect, and gradually and continually release other amounts of drug to maintain this level of therapeutic or prophylactic effect over an extended period of time. In order to maintain this constant level of drug in the body, the drug must be released from the dosage form at a rate that will replace the amount of drug being metabolized and excreted from the body. Controlled-release of an active ingredient can be stimulated by various conditions including, but not limited to, pH, ionic strength, osmotic pressure, temperature, enzymes, water, and other physiological conditions or compounds. 
     A variety of known controlled- or extended-release dosage forms, formulations, and devices can be adapted for use with the salts and compositions of the disclosure. Examples include, but are not limited to, those described in U.S. Pat. Nos. 3,845,770; 3,916,899; 3,536,809; 3,598,123; 4,008,719; 5,674,533; 5,059,595; 5,591,767; 5,120,548; 5,073,543; 5,639,476; 5,354,556; 5,733,566; and 6,365,185 B1; each of which is incorporated herein by reference. These dosage forms can be used to provide slow or controlled-release of one or more active ingredients using, for example, hydroxypropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems (such as OROS® (Alza Corporation, Mountain View, Calif. USA)), or a combination thereof to provide the desired release profile in varying proportions. 
     In some embodiments of any of the aspects, the drug described herein is administered as a monotherapy, e.g., another treatment for the bronchial premalignant lesions is not administered to the subject. 
     In some embodiments of any of the aspects, the methods described herein can further comprise administering a second agent and/or treatment to the subject, e.g. as part of a combinatorial therapy. 
     In certain embodiments, an effective dose of a composition comprising a drug as described herein can be administered to a patient once. In certain embodiments, an effective dose of a composition comprising a drug can be administered to a patient repeatedly. For systemic administration, subjects can be administered a therapeutic amount of a composition comprising a drug, such as, e.g. 0.1 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 40 mg/kg, 50 mg/kg, or more. 
     In some embodiments, after an initial treatment regimen, the treatments can be administered on a less frequent basis. For example, after treatment biweekly for three months, treatment can be repeated once per month, for six months or a year or longer. Treatment according to the methods described herein can reduce levels of a marker or symptom of a condition, e.g. by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80% or at least 90% or more. 
     The dosage of a composition as described herein can be determined by a physician and adjusted, as necessary, to suit observed effects of the treatment. With respect to duration and frequency of treatment, it is typical for skilled clinicians to monitor subjects in order to determine when the treatment is providing therapeutic benefit, and to determine whether to increase or decrease dosage, increase or decrease administration frequency, discontinue treatment, resume treatment, or make other alterations to the treatment regimen. The dosing schedule can vary from once a week to daily depending on a number of clinical factors, such as the subject&#39;s sensitivity to the active ingredient. The desired dose or amount of activation can be administered at one time or divided into subdoses, e.g., 2-4 subdoses and administered over a period of time, e.g., at appropriate intervals through the day or other appropriate schedule. In some embodiments, administration can be chronic, e.g., one or more doses and/or treatments daily over a period of weeks or months. Examples of dosing and/or treatment schedules are administration daily, twice daily, three times daily or four or more times daily over a period of 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, or more. A composition comprising a drug described herein can be administered over a period of time, such as over a 5 minute, 10 minute, 15 minute, 20 minute, or 25 minute period. 
     The dosage ranges for the administration of a drug, according to the methods described herein depend upon, for example, the form of the drug, its potency, and the extent to which symptoms, markers, or indicators of a condition described herein are desired to be reduced, for example the percentage reduction desired for lesion size or the extent to which, for example, lesion subtype changes are desired to be induced. The dosage should not be so large as to cause adverse side effects. Generally, the dosage will vary with the age, condition, and sex of the patient and can be determined by one of skill in the art. The dosage can also be adjusted by the individual physician in the event of any complication. 
     The efficacy of a drug in, e.g. the treatment of a condition described herein, or to induce a response as described herein (e.g. reduction in lesion size) can be determined by the skilled clinician. However, a treatment is considered “effective treatment,” as the term is used herein, if one or more of the signs or symptoms of a condition described herein are altered in a beneficial manner, other clinically accepted symptoms are improved, or even ameliorated, or a desired response is induced e.g., by at least 10% following treatment according to the methods described herein. Efficacy can be assessed, for example, by measuring a marker, indicator, symptom, and/or the incidence of a condition treated according to the methods described herein or any other measurable parameter appropriate. Efficacy can also be measured by a failure of an individual to worsen as assessed by hospitalization, or need for medical interventions (i.e., progression of the disease is halted). Methods of measuring these indicators are known to those of skill in the art and/or are described herein. Treatment includes any treatment of a disease in an individual or an animal (some non-limiting examples include a human or an animal) and includes: (1) inhibiting the disease, e.g., preventing a worsening of symptoms (e.g. pain or inflammation); or (2) relieving the severity of the disease, e.g., causing regression of symptoms. An effective amount for the treatment of a disease means that amount which, when administered to a subject in need thereof, is sufficient to result in effective treatment as that term is defined herein, for that disease. Efficacy of an agent can be determined by assessing physical indicators of a condition or desired response. It is well within the ability of one skilled in the art to monitor efficacy of administration and/or treatment by measuring any one of such parameters, or any combination of parameters. Efficacy can be assessed in animal models of a condition described herein, for example treatment of a mouse model of bronchial premalignant lesions. When using an experimental animal model, efficacy of treatment is evidenced when a statistically significant change in a marker is observed, e.g. lesion size or gene expression. 
     As used herein, “a bronchoscopy-based procedure” refers to any endoscopic technique that permits examination of the bronchus and/or lungs. Bronchoscopy-based procedures can include white light bronchoscopy, autofluorescence bronchoscopy, flexible bronchoscopy, rigid bronchoscopy, bronchoalveolar lavage, and the like. Bronchoscopy-based procedures can further include biopsy, brushing, or tissue sampling. If the 
     In addition to methods of treatment, the methods and biomarker signatures described herein can be applied to methods of predicting the risk of lung cancer in a subject and/or determining the efficacy of treatment or need for further treatment. For example, transition from a proliferative or inflammatory subtype to a normal-like or secretory subtype would indicate that a treatment had been effective or that the treatment can be discontinued. 
     In one aspect of any of the embodiments, described herein is a method of predicting the risk, or the likelihood of progression to lung cancer in a subject, the method comprising: detecting the level of expression of at least one module 5 gene and/or at least one module 6 gene in a sample obtained from the subject, wherein an increased level of expression of at least one module 5 gene as compared to a non-proliferative lesion reference level; and/or a decreased level of expression of at least one module 6 gene as compared to a non-proliferative lesion reference level indicates an increased risk of or likelihood of progressing to lung cancer. In one aspect of any of the embodiments, described herein is a method of predicting the risk, or the likelihood of progression to lung cancer in a subject, the method comprising: detecting the level of expression of at least one module 5 gene and/or at least one module 6 gene in a sample obtained from the subject at a first time point, and detecting the level of expression of at least one module 5 gene and/or at least one module 6 gene in a sample obtained from the subject at a second, subsequent time point, wherein an increased level of expression of at least one module 5 gene over time; and/or a decreased level of expression of at least one module 6 gene over time indicates an increased risk of or likelihood of progressing to lung cancer. 
     In one aspect of any of the embodiments, described herein is a method of predicting the risk, or the likelihood of progression to lung cancer in a subject, the method comprising: detecting the level of expression of at least one module 9 gene and/or at least one module 10 gene in a sample obtained from the subject, wherein an increased level of expression of at least one module 10 gene as compared to a non-proliferative lesion reference level; and/or a decreased level of expression of at least one module 9 gene as compared to a non-proliferative lesion reference level indicates an increased risk of or likelihood of progressing to lung cancer. In one aspect of any of the embodiments, described herein is a method of predicting the risk, or the likelihood of progression to lung cancer in a subject, the method comprising: detecting the level of expression of at least one module 10 gene and/or at least one module 9 gene in a sample obtained from the subject at a first time point, and detecting the level of expression of at least one module 9 gene and/or at least one module 10 gene in a sample obtained from the subject at a second, subsequent time point, wherein an increased level of expression of at least one module 10 gene over time; and/or a decreased level of expression of at least one module 9 gene over time indicates an increased risk of or likelihood of progressing to lung cancer. 
     In one aspect of any of the embodiments, described herein is a method of predicting the risk, or the likelihood of progression to lung cancer in a subject, the method comprising: detecting the level of expression of at least one module 2 gene and/or at least one module 6 gene in a sample obtained from the subject, wherein an increased level of expression of at least one module 2 gene as compared to a non-proliferative lesion reference level; and/or a decreased level of expression of at least one module 6 gene as compared to a non-proliferative lesion reference level indicates an increased risk of or likelihood of progressing to lung cancer. In one aspect of any of the embodiments, described herein is a method of predicting the risk, or the likelihood of progression to lung cancer in a subject, the method comprising: detecting the level of expression of at least one module 2 gene and/or at least one module 6 gene in a sample obtained from the subject at a first time point, and detecting the level of expression of at least one module 2 gene and/or at least one module 6 gene in a sample obtained from the subject at a second, subsequent time point, wherein an increased level of expression of at least one module 2 gene over time; and/or a decreased level of expression of at least one module 6 gene over time indicates an increased risk of or likelihood of progressing to lung cancer. 
     In one aspect of any of the embodiments, described herein is a method of determining treatment efficacy, the method comprising: detecting the level of expression of at least one module 5 gene and/or at least one module 6 gene in a sample obtained from the subject at a first time point, administering a treatment or candidate treatment, and detecting the level of expression of at least one module 5 gene and/or at least one module 6 gene in a sample obtained from the subject at a second, subsequent time point, wherein an decreased level of expression of at least one module 5 gene over time; and/or an increased level of expression of at least one module 6 gene over time indicates the treatment is effective. 
     In one aspect of any of the embodiments, described herein is a method of treatment efficacy, the method comprising: detecting the level of expression of at least one module 10 gene and/or at least one module 9 gene in a sample obtained from the subject at a first time point, administering a treatment or candidate treatment, and detecting the level of expression of at least one module 9 gene and/or at least one module 10 gene in a sample obtained from the subject at a second, subsequent time point, wherein an decreased level of expression of at least one module 10 gene over time; and/or an increased level of expression of at least one module 9 gene over time indicates the treatment is effective. 
     In one aspect of any of the embodiments, described herein is a method of determining treatment efficacy, the method comprising: detecting the level of expression of at least one module 2 gene and/or at least one module 6 gene in a sample obtained from the subject at a first time point, administering a treatment or candidate treatment, and detecting the level of expression of at least one module 2 gene and/or at least one module 6 gene in a sample obtained from the subject at a second, subsequent time point, wherein an decreased level of expression of at least one module 2 gene over time; and/or an increased level of expression of at least one module 6 gene over time indicates the treatment is effective. 
     In one aspect of any of the embodiments, described herein is a method comprising: detecting the level of expression of at least one module 5 gene and/or at least one module 6 gene in a sample obtained from a subject, wherein the level of expression of no more than 1,000 (e.g., no more than 500, 400, 300, 200, or 100) genes is determined. In one aspect of any of the embodiments, described herein is a method comprising: detecting the level of expression of at least one module 9 gene and/or at least one module 10 gene in a sample obtained from a subject, wherein the level of expression of no more than 1,000 (e.g., no more than 500, 400, 300, 200, or 100) genes is determined. In one aspect of any of the embodiments, described herein is a method comprising: detecting the level of expression of at least one module 2 gene and/or at least one module 6 gene in a sample obtained from a subject, wherein the level of expression of no more than 1,000 (e.g., no more than 500, 400, 300, 200, or 100) genes is determined. In some embodiments of any of the aspects, the sample is a bronchial brushing sample. In some embodiments of any of the aspects, the at least one gene is selected from Table 14 or 15. 
     
       
         
           
               
               
               
             
               
                 TABLE 13 
               
               
                   
               
               
                 GeneModule 
                 EnsemblID 
                 GeneSymbols 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 ENSG00000001084 
                 GCLC 
               
               
                 1 
                 ENSG00000006210 
                 CX3CL1 
               
               
                 1 
                 ENSG00000008256 
                 CYTH3 
               
               
                 1 
                 ENSG00000010319 
                 SEMA3G 
               
               
                 1 
                 ENSG00000011028 
                 MRC2 
               
               
                 1 
                 ENSG00000011201 
                 KAL1 
               
               
                 1 
                 ENSG00000011523 
                 CEP68 
               
               
                 1 
                 ENSG00000012660 
                 ELOVL5 
               
               
                 1 
                 ENSG00000017483 
                 SLC38A5 
               
               
                 1 
                 ENSG00000019144 
                 PHLDB1 
               
               
                 1 
                 ENSG00000019549 
                 SNAI2 
               
               
                 1 
                 ENSG00000020181 
                 GPR124 
               
               
                 1 
                 ENSG00000020577 
                 SAMD4A 
               
               
                 1 
                 ENSG00000024422 
                 EHD2 
               
               
                 1 
                 ENSG00000031081 
                 ARHGAP31 
               
               
                 1 
                 ENSG00000035862 
                 TIMP2 
               
               
                 1 
                 ENSG00000042832 
                 TG 
               
               
                 1 
                 ENSG00000049130 
                 KITLG 
               
               
                 1 
                 ENSG00000049540 
                 ELN 
               
               
                 1 
                 ENSG00000050165 
                 DKK3 
               
               
                 1 
                 ENSG00000053747 
                 LAMA3 
               
               
                 1 
                 ENSG00000054965 
                 FAM168A 
               
               
                 1 
                 ENSG00000060140 
                 STYK1 
               
               
                 1 
                 ENSG00000061918 
                 GUCY1B3 
               
               
                 1 
                 ENSG00000063180 
                 CA11 
               
               
                 1 
                 ENSG00000064042 
                 LIMCH1 
               
               
                 1 
                 ENSG00000064205 
                 WISP2 
               
               
                 1 
                 ENSG00000064300 
                 NGFR 
               
               
                 1 
                 ENSG00000064989 
                 CALCRL 
               
               
                 1 
                 ENSG00000065054 
                 SLC9A3R2 
               
               
                 1 
                 ENSG00000065320 
                 NTN1 
               
               
                 1 
                 ENSG00000067445 
                 TRO 
               
               
                 1 
                 ENSG00000069122 
                 GPR116 
               
               
                 1 
                 ENSG00000069188 
                 SDK2 
               
               
                 1 
                 ENSG00000069702 
                 TGFBR3 
               
               
                 1 
                 ENSG00000071246 
                 VASH1 
               
               
                 1 
                 ENSG00000072041 
                 SLC6A15 
               
               
                 1 
                 ENSG00000072195 
                 SPEG 
               
               
                 1 
                 ENSG00000072210 
                 ALDH3A2 
               
               
                 1 
                 ENSG00000072840 
                 EVC 
               
               
                 1 
                 ENSG00000073067 
                 CYP2W1 
               
               
                 1 
                 ENSG00000073282 
                 TP63 
               
               
                 1 
                 ENSG00000073712 
                 FERMT2 
               
               
                 1 
                 ENSG00000074356 
                 C17orf85 
               
               
                 1 
                 ENSG00000074590 
                 NUAK1 
               
               
                 1 
                 ENSG00000074660 
                 SCARF1 
               
               
                 1 
                 ENSG00000076706 
                 MCAM 
               
               
                 1 
                 ENSG00000077782 
                 FGFR1 
               
               
                 1 
                 ENSG00000078018 
                 MAP2 
               
               
                 1 
                 ENSG00000079102 
                 RUNX1T1 
               
               
                 1 
                 ENSG00000079308 
                 TNS1 
               
               
                 1 
                 ENSG00000080573 
                 COL5A3 
               
               
                 1 
                 ENSG00000081052 
                 COL4A4 
               
               
                 1 
                 ENSG00000081913 
                 PHLPP1 
               
               
                 1 
                 ENSG00000082497 
                 SERTAD4 
               
               
                 1 
                 ENSG00000082781 
                 ITGB5 
               
               
                 1 
                 ENSG00000085998 
                 POMGNT1 
               
               
                 1 
                 ENSG00000087116 
                 ADAMTS2 
               
               
                 1 
                 ENSG00000087245 
                 MMP2 
               
               
                 1 
                 ENSG00000088367 
                 EPB41L1 
               
               
                 1 
                 ENSG00000091136 
                 LAMB1 
               
               
                 1 
                 ENSG00000091879 
                 ANGPT2 
               
               
                 1 
                 ENSG00000092096 
                 SLC22A17 
               
               
                 1 
                 ENSG00000092421 
                 SEMA6A 
               
               
                 1 
                 ENSG00000092969 
                 TGFB2 
               
               
                 1 
                 ENSG00000099953 
                 MMP11 
               
               
                 1 
                 ENSG00000100154 
                 TTC28 
               
               
                 1 
                 ENSG00000101331 
                 CCM2L 
               
               
                 1 
                 ENSG00000101665 
                 SMAD7 
               
               
                 1 
                 ENSG00000101825 
                 MXRA5 
               
               
                 1 
                 ENSG00000102302 
                 FGD1 
               
               
                 1 
                 ENSG00000102755 
                 FLT1 
               
               
                 1 
                 ENSG00000103196 
                 CRISPLD2 
               
               
                 1 
                 ENSG00000103241 
                 FOXF1 
               
               
                 1 
                 ENSG00000103723 
                 AP3B2 
               
               
                 1 
                 ENSG00000103852 
                 TTC23 
               
               
                 1 
                 ENSG00000104953 
                 TLE6 
               
               
                 1 
                 ENSG00000105088 
                 OLFM2 
               
               
                 1 
                 ENSG00000105227 
                 PRX 
               
               
                 1 
                 ENSG00000105371 
                 ICAM4 
               
               
                 1 
                 ENSG00000105376 
                 ICAM5 
               
               
                 1 
                 ENSG00000105419 
                 MEIS3 
               
               
                 1 
                 ENSG00000105538 
                 RASIP1 
               
               
                 1 
                 ENSG00000105738 
                 SIPA1L3 
               
               
                 1 
                 ENSG00000105866 
                 SP4 
               
               
                 1 
                 ENSG00000105974 
                 CAV1 
               
               
                 1 
                 ENSG00000106070 
                 GRB10 
               
               
                 1 
                 ENSG00000106123 
                 EPHB6 
               
               
                 1 
                 ENSG00000106333 
                 PCOLCE 
               
               
                 1 
                 ENSG00000106571 
                 GLI3 
               
               
                 1 
                 ENSG00000106624 
                 AEBP1 
               
               
                 1 
                 ENSG00000108821 
                 COL1A1 
               
               
                 1 
                 ENSG00000108852 
                 MPP2 
               
               
                 1 
                 ENSG00000108924 
                 HLF 
               
               
                 1 
                 ENSG00000109099 
                 PMP22 
               
               
                 1 
                 ENSG00000109107 
                 ALDOC 
               
               
                 1 
                 ENSG00000109193 
                 SULT1E1 
               
               
                 1 
                 ENSG00000109610 
                 SOD3 
               
               
                 1 
                 ENSG00000110002 
                 VWA5A 
               
               
                 1 
                 ENSG00000110200 
                 ANAPC15 
               
               
                 1 
                 ENSG00000110799 
                 VWF 
               
               
                 1 
                 ENSG00000110811 
                 LEPREL2 
               
               
                 1 
                 ENSG00000111341 
                 MGP 
               
               
                 1 
                 ENSG00000111452 
                 GPR133 
               
               
                 1 
                 ENSG00000111799 
                 COL12A1 
               
               
                 1 
                 ENSG00000112320 
                 SOBP 
               
               
                 1 
                 ENSG00000112414 
                 GPR126 
               
               
                 1 
                 ENSG00000112562 
                 SMOC2 
               
               
                 1 
                 ENSG00000112769 
                 LAMA4 
               
               
                 1 
                 ENSG00000112782 
                 CLIC5 
               
               
                 1 
                 ENSG00000112902 
                 SEMA5A 
               
               
                 1 
                 ENSG00000112936 
                 C7 
               
               
                 1 
                 ENSG00000112964 
                 GHR 
               
               
                 1 
                 ENSG00000113140 
                 SPARC 
               
               
                 1 
                 ENSG00000113555 
                 PCDH12 
               
               
                 1 
                 ENSG00000114270 
                 COL7A1 
               
               
                 1 
                 ENSG00000114698 
                 PLSCR4 
               
               
                 1 
                 ENSG00000114923 
                 SLC4A3 
               
               
                 1 
                 ENSG00000115252 
                 PDE1A 
               
               
                 1 
                 ENSG00000115306 
                 SPTBN1 
               
               
                 1 
                 ENSG00000115380 
                 EFEMP1 
               
               
                 1 
                 ENSG00000115414 
                 FN1 
               
               
                 1 
                 ENSG00000116016 
                 EPAS1 
               
               
                 1 
                 ENSG00000116678 
                 LEPR 
               
               
                 1 
                 ENSG00000116774 
                 OLFML3 
               
               
                 1 
                 ENSG00000116962 
                 NID1 
               
               
                 1 
                 ENSG00000117013 
                 KCNQ4 
               
               
                 1 
                 ENSG00000117122 
                 MFAP2 
               
               
                 1 
                 ENSG00000117385 
                 LEPRE1 
               
               
                 1 
                 ENSG00000117643 
                 MAN1C1 
               
               
                 1 
                 ENSG00000118495 
                 PLAGL1 
               
               
                 1 
                 ENSG00000119138 
                 KLF9 
               
               
                 1 
                 ENSG00000119681 
                 LTBP2 
               
               
                 1 
                 ENSG00000119699 
                 TGFB3 
               
               
                 1 
                 ENSG00000119771 
                 KLHL29 
               
               
                 1 
                 ENSG00000120156 
                 TEK 
               
               
                 1 
                 ENSG00000120162 
                 MOB3B 
               
               
                 1 
                 ENSG00000120318 
                 ARAP3 
               
               
                 1 
                 ENSG00000120457 
                 KCNJ5 
               
               
                 1 
                 ENSG00000121068 
                 TBX2 
               
               
                 1 
                 ENSG00000121075 
                 TBX4 
               
               
                 1 
                 ENSG00000122035 
                 RASL11A 
               
               
                 1 
                 ENSG00000122642 
                 FKBP9 
               
               
                 1 
                 ENSG00000122707 
                 RECK 
               
               
                 1 
                 ENSG00000122778 
                 KIAA1549 
               
               
                 1 
                 ENSG00000122786 
                 CALD1 
               
               
                 1 
                 ENSG00000123094 
                 RASSF8 
               
               
                 1 
                 ENSG00000123384 
                 LRP1 
               
               
                 1 
                 ENSG00000124006 
                 OBSL1 
               
               
                 1 
                 ENSG00000124406 
                 ATP8A1 
               
               
                 1 
                 ENSG00000125266 
                 EFNB2 
               
               
                 1 
                 ENSG00000125810 
                 CD93 
               
               
                 1 
                 ENSG00000125848 
                 FLRT3 
               
               
                 1 
                 ENSG00000126803 
                 HSPA2 
               
               
                 1 
                 ENSG00000127329 
                 PTPRB 
               
               
                 1 
                 ENSG00000127585 
                 FBXL16 
               
               
                 1 
                 ENSG00000127920 
                 GNG11 
               
               
                 1 
                 ENSG00000127946 
                 HIP1 
               
               
                 1 
                 ENSG00000128052 
                 KDR 
               
               
                 1 
                 ENSG00000128567 
                 PODXL 
               
               
                 1 
                 ENSG00000128641 
                 MYO1B 
               
               
                 1 
                 ENSG00000128656 
                 CHN1 
               
               
                 1 
                 ENSG00000128791 
                 TWSG1 
               
               
                 1 
                 ENSG00000128872 
                 TMOD2 
               
               
                 1 
                 ENSG00000128917 
                 DLL4 
               
               
                 1 
                 ENSG00000129009 
                 ISLR 
               
               
                 1 
                 ENSG00000129038 
                 LOXL1 
               
               
                 1 
                 ENSG00000129467 
                 ADCY4 
               
               
                 1 
                 ENSG00000129474 
                 AJUBA 
               
               
                 1 
                 ENSG00000129946 
                 SHC2 
               
               
                 1 
                 ENSG00000129990 
                 SYT5 
               
               
                 1 
                 ENSG00000130052 
                 STARD8 
               
               
                 1 
                 ENSG00000130300 
                 PLVAP 
               
               
                 1 
                 ENSG00000130508 
                 PXDN 
               
               
                 1 
                 ENSG00000130635 
                 COL5A1 
               
               
                 1 
                 ENSG00000131016 
                 AKAP12 
               
               
                 1 
                 ENSG00000131477 
                 RAMP2 
               
               
                 1 
                 ENSG00000131831 
                 RAI2 
               
               
                 1 
                 ENSG00000132688 
                 NES 
               
               
                 1 
                 ENSG00000133026 
                 MYH10 
               
               
                 1 
                 ENSG00000133067 
                 LGR6 
               
               
                 1 
                 ENSG00000133110 
                 POSTN 
               
               
                 1 
                 ENSG00000133121 
                 STARD13 
               
               
                 1 
                 ENSG00000133313 
                 CNDP2 
               
               
                 1 
                 ENSG00000133687 
                 TMTC1 
               
               
                 1 
                 ENSG00000134243 
                 SORT1 
               
               
                 1 
                 ENSG00000134245 
                 WNT2B 
               
               
                 1 
                 ENSG00000134318 
                 ROCK2 
               
               
                 1 
                 ENSG00000134352 
                 IL6ST 
               
               
                 1 
                 ENSG00000134569 
                 LRP4 
               
               
                 1 
                 ENSG00000134590 
                 FAM127A 
               
               
                 1 
                 ENSG00000134627 
                 PIWIL4 
               
               
                 1 
                 ENSG00000134802 
                 SLC43A3 
               
               
                 1 
                 ENSG00000134853 
                 PDGFRA 
               
               
                 1 
                 ENSG00000134917 
                 ADAMTS8 
               
               
                 1 
                 ENSG00000134986 
                 NREP 
               
               
                 1 
                 ENSG00000135063 
                 FAM189A2 
               
               
                 1 
                 ENSG00000135111 
                 TBX3 
               
               
                 1 
                 ENSG00000135423 
                 GLS2 
               
               
                 1 
                 ENSG00000135424 
                 ITGA7 
               
               
                 1 
                 ENSG00000135775 
                 COG2 
               
               
                 1 
                 ENSG00000135862 
                 LAMC1 
               
               
                 1 
                 ENSG00000135925 
                 WNT10A 
               
               
                 1 
                 ENSG00000136114 
                 THSD1 
               
               
                 1 
                 ENSG00000136158 
                 SPRY2 
               
               
                 1 
                 ENSG00000136160 
                 EDNRB 
               
               
                 1 
                 ENSG00000136205 
                 TNS3 
               
               
                 1 
                 ENSG00000136274 
                 NACAD 
               
               
                 1 
                 ENSG00000136546 
                 SCN7A 
               
               
                 1 
                 ENSG00000137273 
                 FOXF2 
               
               
                 1 
                 ENSG00000137834 
                 SMAD6 
               
               
                 1 
                 ENSG00000137872 
                 SEMA6D 
               
               
                 1 
                 ENSG00000137962 
                 ARHGAP29 
               
               
                 1 
                 ENSG00000138356 
                 AOX1 
               
               
                 1 
                 ENSG00000138495 
                 COX17 
               
               
                 1 
                 ENSG00000138735 
                 PDE5A 
               
               
                 1 
                 ENSG00000138792 
                 ENPEP 
               
               
                 1 
                 ENSG00000138795 
                 LEF1 
               
               
                 1 
                 ENSG00000139174 
                 PRICKLE1 
               
               
                 1 
                 ENSG00000139211 
                 AMIGO2 
               
               
                 1 
                 ENSG00000139263 
                 LRIG3 
               
               
                 1 
                 ENSG00000140092 
                 FBLN5 
               
               
                 1 
                 ENSG00000140682 
                 TGFB1I1 
               
               
                 1 
                 ENSG00000140807 
                 NKD1 
               
               
                 1 
                 ENSG00000140937 
                 CDH11 
               
               
                 1 
                 ENSG00000141338 
                 ABCA8 
               
               
                 1 
                 ENSG00000141622 
                 RNF165 
               
               
                 1 
                 ENSG00000141720 
                 PIP4K2B 
               
               
                 1 
                 ENSG00000141756 
                 FKBP10 
               
               
                 1 
                 ENSG00000142156 
                 COL6A1 
               
               
                 1 
                 ENSG00000142173 
                 COL6A2 
               
               
                 1 
                 ENSG00000142798 
                 HSPG2 
               
               
                 1 
                 ENSG00000143067 
                 ZNF697 
               
               
                 1 
                 ENSG00000143140 
                 GJA5 
               
               
                 1 
                 ENSG00000143341 
                 HMCN1 
               
               
                 1 
                 ENSG00000143995 
                 MEIS1 
               
               
                 1 
                 ENSG00000144057 
                 ST6GAL2 
               
               
                 1 
                 ENSG00000144642 
                 RBMS3 
               
               
                 1 
                 ENSG00000144724 
                 PTPRG 
               
               
                 1 
                 ENSG00000144810 
                 COL8A1 
               
               
                 1 
                 ENSG00000144857 
                 BOC 
               
               
                 1 
                 ENSG00000145040 
                 UCN2 
               
               
                 1 
                 ENSG00000145147 
                 SLIT2 
               
               
                 1 
                 ENSG00000145675 
                 PIK3R1 
               
               
                 1 
                 ENSG00000145777 
                 TSLP 
               
               
                 1 
                 ENSG00000146648 
                 EGFR 
               
               
                 1 
                 ENSG00000146966 
                 DENND2A 
               
               
                 1 
                 ENSG00000147027 
                 TMEM47 
               
               
                 1 
                 ENSG00000147257 
                 GPC3 
               
               
                 1 
                 ENSG00000147408 
                 CSGALNACT1 
               
               
                 1 
                 ENSG00000147862 
                 NFIB 
               
               
                 1 
                 ENSG00000148468 
                 FAM171A1 
               
               
                 1 
                 ENSG00000148541 
                 FAM13C 
               
               
                 1 
                 ENSG00000148600 
                 CDHR1 
               
               
                 1 
                 ENSG00000149212 
                 SESN3 
               
               
                 1 
                 ENSG00000149294 
                 NCAM1 
               
               
                 1 
                 ENSG00000149485 
                 FADS1 
               
               
                 1 
                 ENSG00000149564 
                 ESAM 
               
               
                 1 
                 ENSG00000149575 
                 SCN2B 
               
               
                 1 
                 ENSG00000149582 
                 TMEM25 
               
               
                 1 
                 ENSG00000149596 
                 JPH2 
               
               
                 1 
                 ENSG00000149639 
                 SOGA1 
               
               
                 1 
                 ENSG00000150048 
                 CLEC1A 
               
               
                 1 
                 ENSG00000150457 
                 LATS2 
               
               
                 1 
                 ENSG00000150471 
                 LPHN3 
               
               
                 1 
                 ENSG00000150625 
                 GPM6A 
               
               
                 1 
                 ENSG00000150938 
                 CRIM1 
               
               
                 1 
                 ENSG00000151617 
                 EDNRA 
               
               
                 1 
                 ENSG00000151632 
                 AKR1C2 
               
               
                 1 
                 ENSG00000151914 
                 DST 
               
               
                 1 
                 ENSG00000152104 
                 PTPN14 
               
               
                 1 
                 ENSG00000152217 
                 SETBP1 
               
               
                 1 
                 ENSG00000152583 
                 SPARCL1 
               
               
                 1 
                 ENSG00000152990 
                 GPR125 
               
               
                 1 
                 ENSG00000153162 
                 BMP6 
               
               
                 1 
                 ENSG00000153208 
                 MERTK 
               
               
                 1 
                 ENSG00000153253 
                 SCN3A 
               
               
                 1 
                 ENSG00000153885 
                 KCTD15 
               
               
                 1 
                 ENSG00000154065 
                 ANKRD29 
               
               
                 1 
                 ENSG00000154122 
                 ANKH 
               
               
                 1 
                 ENSG00000154133 
                 ROBO4 
               
               
                 1 
                 ENSG00000154188 
                 ANGPT1 
               
               
                 1 
                 ENSG00000154310 
                 TNIK 
               
               
                 1 
                 ENSG00000154342 
                 WNT3A 
               
               
                 1 
                 ENSG00000154358 
                 OBSCN 
               
               
                 1 
                 ENSG00000154767 
                 XPC 
               
               
                 1 
                 ENSG00000154783 
                 FGD5 
               
               
                 1 
                 ENSG00000155254 
                 MARVELD1 
               
               
                 1 
                 ENSG00000155324 
                 GRAMD3 
               
               
                 1 
                 ENSG00000156011 
                 PSD3 
               
               
                 1 
                 ENSG00000156298 
                 TSPAN7 
               
               
                 1 
                 ENSG00000156966 
                 B3GNT7 
               
               
                 1 
                 ENSG00000157240 
                 FZD1 
               
               
                 1 
                 ENSG00000157404 
                 KIT 
               
               
                 1 
                 ENSG00000157510 
                 AFAP1L1 
               
               
                 1 
                 ENSG00000157554 
                 ERG 
               
               
                 1 
                 ENSG00000158270 
                 COLEC12 
               
               
                 1 
                 ENSG00000158301 
                 GPRASP2 
               
               
                 1 
                 ENSG00000158352 
                 SHROOM4 
               
               
                 1 
                 ENSG00000158435 
                 CNOT11 
               
               
                 1 
                 ENSG00000159164 
                 SV2A 
               
               
                 1 
                 ENSG00000159640 
                 ACE 
               
               
                 1 
                 ENSG00000159692 
                 CTBP1 
               
               
                 1 
                 ENSG00000160190 
                 SLC37A1 
               
               
                 1 
                 ENSG00000160191 
                 PDE9A 
               
               
                 1 
                 ENSG00000160469 
                 BRSK1 
               
               
                 1 
                 ENSG00000160867 
                 FGFR4 
               
               
                 1 
                 ENSG00000161940 
                 BCL6B 
               
               
                 1 
                 ENSG00000162367 
                 TAL1 
               
               
                 1 
                 ENSG00000162407 
                 PPAP2B 
               
               
                 1 
                 ENSG00000162493 
                 PDPN 
               
               
                 1 
                 ENSG00000162552 
                 WNT4 
               
               
                 1 
                 ENSG00000162576 
                 MXRA8 
               
               
                 1 
                 ENSG00000162591 
                 MEGF6 
               
               
                 1 
                 ENSG00000162599 
                 NFIA 
               
               
                 1 
                 ENSG00000162618 
                 ELTD1 
               
               
                 1 
                 ENSG00000162627 
                 SNX7 
               
               
                 1 
                 ENSG00000162729 
                 IGSF8 
               
               
                 1 
                 ENSG00000162733 
                 DDR2 
               
               
                 1 
                 ENSG00000162817 
                 C1orf115 
               
               
                 1 
                 ENSG00000163072 
                 NOSTRIN 
               
               
                 1 
                 ENSG00000163273 
                 NPPC 
               
               
                 1 
                 ENSG00000163328 
                 GPR155 
               
               
                 1 
                 ENSG00000163359 
                 COL6A3 
               
               
                 1 
                 ENSG00000163378 
                 EOGT 
               
               
                 1 
                 ENSG00000163430 
                 FSTL1 
               
               
                 1 
                 ENSG00000163435 
                 ELF3 
               
               
                 1 
                 ENSG00000163520 
                 FBLN2 
               
               
                 1 
                 ENSG00000163710 
                 PCOLCE2 
               
               
                 1 
                 ENSG00000163827 
                 LRRC2 
               
               
                 1 
                 ENSG00000164056 
                 SPRY1 
               
               
                 1 
                 ENSG00000164116 
                 GUCY1A3 
               
               
                 1 
                 ENSG00000164176 
                 EDIL3 
               
               
                 1 
                 ENSG00000164488 
                 DACT2 
               
               
                 1 
                 ENSG00000164692 
                 COL1A2 
               
               
                 1 
                 ENSG00000164741 
                 DLC1 
               
               
                 1 
                 ENSG00000165125 
                 TRPV6 
               
               
                 1 
                 ENSG00000165659 
                 DACH1 
               
               
                 1 
                 ENSG00000165757 
                 KIAA1462 
               
               
                 1 
                 ENSG00000165821 
                 SALL2 
               
               
                 1 
                 ENSG00000165995 
                 CACNB2 
               
               
                 1 
                 ENSG00000166025 
                 AMOTL1 
               
               
                 1 
                 ENSG00000166086 
                 JAM3 
               
               
                 1 
                 ENSG00000166105 
                 GLB1L3 
               
               
                 1 
                 ENSG00000166147 
                 FBN1 
               
               
                 1 
                 ENSG00000166257 
                 SCN3B 
               
               
                 1 
                 ENSG00000166265 
                 CYYR1 
               
               
                 1 
                 ENSG00000166292 
                 TMEM100 
               
               
                 1 
                 ENSG00000166398 
                 KIAA0355 
               
               
                 1 
                 ENSG00000166482 
                 MFAP4 
               
               
                 1 
                 ENSG00000166813 
                 KIF7 
               
               
                 1 
                 ENSG00000166886 
                 NAB2 
               
               
                 1 
                 ENSG00000167123 
                 CERCAM 
               
               
                 1 
                 ENSG00000168056 
                 LTBP3 
               
               
                 1 
                 ENSG00000168060 
                 NAALADL1 
               
               
                 1 
                 ENSG00000168077 
                 SCARA3 
               
               
                 1 
                 ENSG00000168264 
                 IRF2BP2 
               
               
                 1 
                 ENSG00000168490 
                 PHYHIP 
               
               
                 1 
                 ENSG00000168497 
                 SDPR 
               
               
                 1 
                 ENSG00000168502 
                 SOGA2 
               
               
                 1 
                 ENSG00000168542 
                 COL3A1 
               
               
                 1 
                 ENSG00000168621 
                 GDNF 
               
               
                 1 
                 ENSG00000168818 
                 STX18 
               
               
                 1 
                 ENSG00000168890 
                 TMEM150A 
               
               
                 1 
                 ENSG00000169047 
                 IRS1 
               
               
                 1 
                 ENSG00000169291 
                 SHE 
               
               
                 1 
                 ENSG00000169302 
                 STK32A 
               
               
                 1 
                 ENSG00000169418 
                 NPR1 
               
               
                 1 
                 ENSG00000169435 
                 RASSF6 
               
               
                 1 
                 ENSG00000169504 
                 CLIC4 
               
               
                 1 
                 ENSG00000169604 
                 ANTXR1 
               
               
                 1 
                 ENSG00000169744 
                 LDB2 
               
               
                 1 
                 ENSG00000170017 
                 ALCAM 
               
               
                 1 
                 ENSG00000170364 
                 SETMAR 
               
               
                 1 
                 ENSG00000170549 
                 IRX1 
               
               
                 1 
                 ENSG00000170558 
                 CDH2 
               
               
                 1 
                 ENSG00000170915 
                 PAQR8 
               
               
                 1 
                 ENSG00000171016 
                 PYGO1 
               
               
                 1 
                 ENSG00000171033 
                 PKIA 
               
               
                 1 
                 ENSG00000171243 
                 SOSTDC1 
               
               
                 1 
                 ENSG00000171346 
                 KRT15 
               
               
                 1 
                 ENSG00000171444 
                 MCC 
               
               
                 1 
                 ENSG00000171462 
                 DLK2 
               
               
                 1 
                 ENSG00000171791 
                 BCL2 
               
               
                 1 
                 ENSG00000171812 
                 COL8A2 
               
               
                 1 
                 ENSG00000171867 
                 PRNP 
               
               
                 1 
                 ENSG00000172348 
                 RCAN2 
               
               
                 1 
                 ENSG00000172458 
                 IL17D 
               
               
                 1 
                 ENSG00000172638 
                 EFEMP2 
               
               
                 1 
                 ENSG00000172889 
                 EGFL7 
               
               
                 1 
                 ENSG00000173040 
                 EVC2 
               
               
                 1 
                 ENSG00000173210 
                 ABLIM3 
               
               
                 1 
                 ENSG00000173269 
                 MMRN2 
               
               
                 1 
                 ENSG00000173546 
                 CSPG4 
               
               
                 1 
                 ENSG00000173706 
                 HEG1 
               
               
                 1 
                 ENSG00000173805 
                 HAP1 
               
               
                 1 
                 ENSG00000174059 
                 CD34 
               
               
                 1 
                 ENSG00000174226 
                 SNX31 
               
               
                 1 
                 ENSG00000174348 
                 PODN 
               
               
                 1 
                 ENSG00000174370 
                 C11orf45 
               
               
                 1 
                 ENSG00000174567 
                 GOLT1A 
               
               
                 1 
                 ENSG00000174640 
                 SLCO2A1 
               
               
                 1 
                 ENSG00000175471 
                 MCTP1 
               
               
                 1 
                 ENSG00000175920 
                 DOK7 
               
               
                 1 
                 ENSG00000176393 
                 RNPEP 
               
               
                 1 
                 ENSG00000176428 
                 VPS37D 
               
               
                 1 
                 ENSG00000176435 
                 CLEC14A 
               
               
                 1 
                 ENSG00000176771 
                 NCKAP5 
               
               
                 1 
                 ENSG00000176971 
                 FIBIN 
               
               
                 1 
                 ENSG00000177076 
                 ACER2 
               
               
                 1 
                 ENSG00000177303 
                 CASKIN2 
               
               
                 1 
                 ENSG00000177469 
                 PTRF 
               
               
                 1 
                 ENSG00000177707 
                 PVRL3 
               
               
                 1 
                 ENSG00000177732 
                 SOX12 
               
               
                 1 
                 ENSG00000178031 
                 ADAMTSL1 
               
               
                 1 
                 ENSG00000178222 
                 RNF212 
               
               
                 1 
                 ENSG00000178947 
                 LINC00086 
               
               
                 1 
                 ENSG00000179104 
                 TMTC2 
               
               
                 1 
                 ENSG00000179348 
                 GATA2 
               
               
                 1 
                 ENSG00000179431 
                 FJX1 
               
               
                 1 
                 ENSG00000179776 
                 CDH5 
               
               
                 1 
                 ENSG00000180739 
                 S1PR5 
               
               
                 1 
                 ENSG00000180875 
                 GREM2 
               
               
                 1 
                 ENSG00000181104 
                 F2R 
               
               
                 1 
                 ENSG00000182175 
                 RGMA 
               
               
                 1 
                 ENSG00000182272 
                 B4GALNT4 
               
               
                 1 
                 ENSG00000182492 
                 BGN 
               
               
                 1 
                 ENSG00000182534 
                 MXRA7 
               
               
                 1 
                 ENSG00000182621 
                 PLCB1 
               
               
                 1 
                 ENSG00000182871 
                 COL18A1 
               
               
                 1 
                 ENSG00000182985 
                 CADM1 
               
               
                 1 
                 ENSG00000183087 
                 GAS6 
               
               
                 1 
                 ENSG00000183160 
                 TMEM119 
               
               
                 1 
                 ENSG00000183722 
                 LHFP 
               
               
                 1 
                 ENSG00000183729 
                 NPBWR1 
               
               
                 1 
                 ENSG00000183734 
                 ASCL2 
               
               
                 1 
                 ENSG00000183853 
                 KIRREL 
               
               
                 1 
                 ENSG00000183963 
                 SMTN 
               
               
                 1 
                 ENSG00000184113 
                 CLDN5 
               
               
                 1 
                 ENSG00000184564 
                 SLITRK6 
               
               
                 1 
                 ENSG00000184916 
                 JAG2 
               
               
                 1 
                 ENSG00000184985 
                 SORCS2 
               
               
                 1 
                 ENSG00000185070 
                 FLRT2 
               
               
                 1 
                 ENSG00000185418 
                 TARSL2 
               
               
                 1 
                 ENSG00000185652 
                 NTF3 
               
               
                 1 
                 ENSG00000185668 
                 POU3F1 
               
               
                 1 
                 ENSG00000185924 
                 RTN4RL1 
               
               
                 1 
                 ENSG00000186260 
                 MKL2 
               
               
                 1 
                 ENSG00000186318 
                 BACE1 
               
               
                 1 
                 ENSG00000186462 
                 NAP1L2 
               
               
                 1 
                 ENSG00000186732 
                 MPPED1 
               
               
                 1 
                 ENSG00000186994 
                 KANK3 
               
               
                 1 
                 ENSG00000186998 
                 EMID1 
               
               
                 1 
                 ENSG00000187068 
                 C3orf70 
               
               
                 1 
                 ENSG00000187134 
                 AKR1C1 
               
               
                 1 
                 ENSG00000187193 
                 MT1X 
               
               
                 1 
                 ENSG00000187244 
                 BCAM 
               
               
                 1 
                 ENSG00000187513 
                 GJA4 
               
               
                 1 
                 ENSG00000187678 
                 SPRY4 
               
               
                 1 
                 ENSG00000187720 
                 THSD4 
               
               
                 1 
                 ENSG00000187955 
                 COL14A1 
               
               
                 1 
                 ENSG00000188153 
                 COL4A5 
               
               
                 1 
                 ENSG00000188677 
                 PARVB 
               
               
                 1 
                 ENSG00000189376 
                 C8orf76 
               
               
                 1 
                 ENSG00000196139 
                 AKR1C3 
               
               
                 1 
                 ENSG00000196569 
                 LAMA2 
               
               
                 1 
                 ENSG00000197256 
                 KANK2 
               
               
                 1 
                 ENSG00000197321 
                 SVIL 
               
               
                 1 
                 ENSG00000197380 
                 DACT3 
               
               
                 1 
                 ENSG00000197461 
                 PDGFA 
               
               
                 1 
                 ENSG00000197467 
                 COL13A1 
               
               
                 1 
                 ENSG00000197496 
                 SLC2A10 
               
               
                 1 
                 ENSG00000197565 
                 COL4A6 
               
               
                 1 
                 ENSG00000197614 
                 MFAP5 
               
               
                 1 
                 ENSG00000197696 
                 NMB 
               
               
                 1 
                 ENSG00000198300 
                 PEG3 
               
               
                 1 
                 ENSG00000198719 
                 DLL1 
               
               
                 1 
                 ENSG00000198728 
                 LDB1 
               
               
                 1 
                 ENSG00000198835 
                 GJC2 
               
               
                 1 
                 ENSG00000198853 
                 RUSC2 
               
               
                 1 
                 ENSG00000198873 
                 GRK5 
               
               
                 1 
                 ENSG00000198885 
                 ITPRIPL1 
               
               
                 1 
                 ENSG00000204175 
                 GPRIN2 
               
               
                 1 
                 ENSG00000204262 
                 COL5A2 
               
               
                 1 
                 ENSG00000204301 
                 NOTCH4 
               
               
                 1 
                 ENSG00000205795 
                 CYS1 
               
               
                 1 
                 ENSG00000211450 
                 C11orf31 
               
               
                 1 
                 ENSG00000212747 
                 FAM127C 
               
               
                 1 
                 ENSG00000213689 
                 TREX1 
               
               
                 1 
                 ENSG00000213903 
                 LTB4R 
               
               
                 1 
                 ENSG00000214860 
                 EVPLL 
               
               
                 1 
                 ENSG00000215218 
                 UBE2QL1 
               
               
                 1 
                 ENSG00000221866 
                 PLXNA4 
               
               
                 1 
                 ENSG00000221968 
                 FADS3 
               
               
                 1 
                 ENSG00000224652 
                 LINC00885 
               
               
                 1 
                 ENSG00000225950 
                 NTF4 
               
               
                 1 
                 ENSG00000229852 
               
               
                 1 
                 ENSG00000230937 
                 MIR205HG 
               
               
                 1 
                 ENSG00000231789 
               
               
                 1 
                 ENSG00000239911 
                 PRKAG2-AS1 
               
               
                 1 
                 ENSG00000240583 
                 AQP1 
               
               
                 1 
                 ENSG00000240771 
                 ARHGEF25 
               
               
                 1 
                 ENSG00000241127 
                 YAE1D1 
               
               
                 1 
                 ENSG00000241644 
                 INMT 
               
               
                 1 
                 ENSG00000243244 
                 STON1 
               
               
                 1 
                 ENSG00000250685 
               
               
                 1 
                 ENSG00000251322 
                 SHANK3 
               
               
                 1 
                 ENSG00000256309 
               
               
                 1 
                 ENSG00000257026 
               
               
                 1 
                 ENSG00000269113 
                 TRABD2B 
               
               
                 1 
                 ENSG00000269190 
                 FBXO17 
               
               
                 1 
                 ENSG00000269905 
               
               
                 1 
                 ENSG00000272327 
               
               
                 1 
                 ENSG00000272734 
                 ADIRF-AS1 
               
               
                 2 
                 ENSG00000001631 
                 KRIT1 
               
               
                 2 
                 ENSG00000002016 
                 RAD52 
               
               
                 2 
                 ENSG00000003756 
                 RBM5 
               
               
                 2 
                 ENSG00000004534 
                 RBM6 
               
               
                 2 
                 ENSG00000004777 
                 ARHGAP33 
               
               
                 2 
                 ENSG00000006025 
                 OSBPL7 
               
               
                 2 
                 ENSG00000006194 
                 ZNF263 
               
               
                 2 
                 ENSG00000006530 
                 AGK 
               
               
                 2 
                 ENSG00000007392 
                 LUC7L 
               
               
                 2 
                 ENSG00000008128 
                 CDK11A 
               
               
                 2 
                 ENSG00000009724 
                 MASP2 
               
               
                 2 
                 ENSG00000011021 
                 CLCN6 
               
               
                 2 
                 ENSG00000011243 
                 AKAP8L 
               
               
                 2 
                 ENSG00000011376 
                 LARS2 
               
               
                 2 
                 ENSG00000013441 
                 CLK1 
               
               
                 2 
                 ENSG00000013561 
                 RNF14 
               
               
                 2 
                 ENSG00000018189 
                 RUFY3 
               
               
                 2 
                 ENSG00000028310 
                 BRD9 
               
               
                 2 
                 ENSG00000032219 
                 ARID4A 
               
               
                 2 
                 ENSG00000033030 
                 ZCCHC8 
               
               
                 2 
                 ENSG00000038358 
                 EDC4 
               
               
                 2 
                 ENSG00000044446 
                 PHKA2 
               
               
                 2 
                 ENSG00000047634 
                 SCML1 
               
               
                 2 
                 ENSG00000051009 
                 FAM160A2 
               
               
                 2 
                 ENSG00000053438 
                 NNAT 
               
               
                 2 
                 ENSG00000055955 
                 ITIH4 
               
               
                 2 
                 ENSG00000056558 
                 TRAF1 
               
               
                 2 
                 ENSG00000058673 
                 ZC3H11A 
               
               
                 2 
                 ENSG00000059588 
                 TARBP1 
               
               
                 2 
                 ENSG00000061936 
                 SFSWAP 
               
               
                 2 
                 ENSG00000061987 
                 MON2 
               
               
                 2 
                 ENSG00000064607 
                 SUGP2 
               
               
                 2 
                 ENSG00000064687 
                 ABCA7 
               
               
                 2 
                 ENSG00000067191 
                 CACNB1 
               
               
                 2 
                 ENSG00000068697 
                 LAPTM4A 
               
               
                 2 
                 ENSG00000068745 
                 IP6K2 
               
               
                 2 
                 ENSG00000069493 
                 CLEC2D 
               
               
                 2 
                 ENSG00000070476 
                 ZXDC 
               
               
                 2 
                 ENSG00000070610 
                 GBA2 
               
               
                 2 
                 ENSG00000070669 
                 ASNS 
               
               
                 2 
                 ENSG00000073605 
                 GSDMB 
               
               
                 2 
                 ENSG00000074582 
                 BCS1L 
               
               
                 2 
                 ENSG00000074696 
                 PTPLAD1 
               
               
                 2 
                 ENSG00000075413 
                 MARK3 
               
               
                 2 
                 ENSG00000075826 
                 SEC31B 
               
               
                 2 
                 ENSG00000077458 
                 FAM76B 
               
               
                 2 
                 ENSG00000078403 
                 MLLT10 
               
               
                 2 
                 ENSG00000079134 
                 THOC1 
               
               
                 2 
                 ENSG00000081019 
                 RSBN1 
               
               
                 2 
                 ENSG00000081665 
                 ZNF506 
               
               
                 2 
                 ENSG00000081791 
                 KIAA0141 
               
               
                 2 
                 ENSG00000082258 
                 CCNT2 
               
               
                 2 
                 ENSG00000084463 
                 WBP11 
               
               
                 2 
                 ENSG00000085465 
                 OVGP1 
               
               
                 2 
                 ENSG00000087087 
                 SRRT 
               
               
                 2 
                 ENSG00000087157 
                 PGS1 
               
               
                 2 
                 ENSG00000088038 
                 CNOT3 
               
               
                 2 
                 ENSG00000088448 
                 ANKRD10 
               
               
                 2 
                 ENSG00000089280 
                 FUS 
               
               
                 2 
                 ENSG00000090432 
                 MUL1 
               
               
                 2 
                 ENSG00000090905 
                 TNRC6A 
               
               
                 2 
                 ENSG00000092094 
                 OSGEP 
               
               
                 2 
                 ENSG00000092529 
                 CAPN3 
               
               
                 2 
                 ENSG00000094631 
                 HDAC6 
               
               
                 2 
                 ENSG00000094914 
                 AAAS 
               
               
                 2 
                 ENSG00000095066 
                 HOOK2 
               
               
                 2 
                 ENSG00000095564 
                 BTAF1 
               
               
                 2 
                 ENSG00000099251 
                 HSD17B7P2 
               
               
                 2 
                 ENSG00000099940 
                 SNAP29 
               
               
                 2 
                 ENSG00000099949 
                 LZTR1 
               
               
                 2 
                 ENSG00000100038 
                 TOP3B 
               
               
                 2 
                 ENSG00000100068 
                 LRP5L 
               
               
                 2 
                 ENSG00000100197 
                 CYP2D6 
               
               
                 2 
                 ENSG00000100201 
                 DDX17 
               
               
                 2 
                 ENSG00000100288 
                 CHKB 
               
               
                 2 
                 ENSG00000100416 
                 TRMU 
               
               
                 2 
                 ENSG00000100445 
                 SDR39U1 
               
               
                 2 
                 ENSG00000100483 
                 VCPKMT 
               
               
                 2 
                 ENSG00000100650 
                 SRSF5 
               
               
                 2 
                 ENSG00000100726 
                 TELO2 
               
               
                 2 
                 ENSG00000100813 
                 ACIN1 
               
               
                 2 
                 ENSG00000100836 
                 PABPN1 
               
               
                 2 
                 ENSG00000100941 
                 PNN 
               
               
                 2 
                 ENSG00000101049 
                 SGK2 
               
               
                 2 
                 ENSG00000101104 
                 PABPC1L 
               
               
                 2 
                 ENSG00000101901 
                 ALG13 
               
               
                 2 
                 ENSG00000102057 
                 KCND1 
               
               
                 2 
                 ENSG00000102125 
                 TAZ 
               
               
                 2 
                 ENSG00000102287 
                 GABRE 
               
               
                 2 
                 ENSG00000102878 
                 HSF4 
               
               
                 2 
                 ENSG00000102901 
                 CENPT 
               
               
                 2 
                 ENSG00000102908 
                 NFAT5 
               
               
                 2 
                 ENSG00000103091 
                 WDR59 
               
               
                 2 
                 ENSG00000103168 
                 TAF1C 
               
               
                 2 
                 ENSG00000104365 
                 IKBKB 
               
               
                 2 
                 ENSG00000104852 
                 SNRNP70 
               
               
                 2 
                 ENSG00000104957 
                 CCDC130 
               
               
                 2 
                 ENSG00000105127 
                 AKAP8 
               
               
                 2 
                 ENSG00000105136 
                 ZNF419 
               
               
                 2 
                 ENSG00000105612 
                 DNASE2 
               
               
                 2 
                 ENSG00000105875 
                 WDR91 
               
               
                 2 
                 ENSG00000106133 
                 NSUN5P2 
               
               
                 2 
                 ENSG00000106344 
                 RBM28 
               
               
                 2 
                 ENSG00000106608 
                 URGCP 
               
               
                 2 
                 ENSG00000106635 
                 BCL7B 
               
               
                 2 
                 ENSG00000108100 
                 CCNY 
               
               
                 2 
                 ENSG00000108296 
                 CWC25 
               
               
                 2 
                 ENSG00000108389 
                 MTMR4 
               
               
                 2 
                 ENSG00000108465 
                 CDK5RAP3 
               
               
                 2 
                 ENSG00000108474 
                 PIGL 
               
               
                 2 
                 ENSG00000108654 
                 DDX5 
               
               
                 2 
                 ENSG00000108773 
                 KAT2A 
               
               
                 2 
                 ENSG00000108799 
                 EZH1 
               
               
                 2 
                 ENSG00000108848 
                 LUC7L3 
               
               
                 2 
                 ENSG00000108963 
                 DPH1 
               
               
                 2 
                 ENSG00000109046 
                 WSB1 
               
               
                 2 
                 ENSG00000109063 
                 MYH3 
               
               
                 2 
                 ENSG00000109920 
                 FNBP4 
               
               
                 2 
                 ENSG00000110066 
                 SUV420H1 
               
               
                 2 
                 ENSG00000110455 
                 ACCS 
               
               
                 2 
                 ENSG00000110721 
                 CHKA 
               
               
                 2 
                 ENSG00000110888 
                 CAPRIN2 
               
               
                 2 
                 ENSG00000111011 
                 RSRC2 
               
               
                 2 
                 ENSG00000111203 
                 ITFG2 
               
               
                 2 
                 ENSG00000111231 
                 GPN3 
               
               
                 2 
                 ENSG00000111271 
                 ACAD10 
               
               
                 2 
                 ENSG00000111364 
                 DDX55 
               
               
                 2 
                 ENSG00000111664 
                 GNB3 
               
               
                 2 
                 ENSG00000111785 
                 RIC8B 
               
               
                 2 
                 ENSG00000111788 
               
               
                 2 
                 ENSG00000112309 
                 B3GAT2 
               
               
                 2 
                 ENSG00000112357 
                 PEX7 
               
               
                 2 
                 ENSG00000112983 
                 BRD8 
               
               
                 2 
                 ENSG00000113108 
                 APBB3 
               
               
                 2 
                 ENSG00000113240 
                 CLK4 
               
               
                 2 
                 ENSG00000113649 
                 TCERG1 
               
               
                 2 
                 ENSG00000113971 
                 NPHP3 
               
               
                 2 
                 ENSG00000114742 
                 WDR48 
               
               
                 2 
                 ENSG00000114770 
                 ABCC5 
               
               
                 2 
                 ENSG00000114857 
                 NKTR 
               
               
                 2 
                 ENSG00000114982 
                 KANSL3 
               
               
                 2 
                 ENSG00000115234 
                 SNX17 
               
               
                 2 
                 ENSG00000115282 
                 TTC31 
               
               
                 2 
                 ENSG00000115459 
                 ELMOD3 
               
               
                 2 
                 ENSG00000115524 
                 SF3B1 
               
               
                 2 
                 ENSG00000115875 
                 SRSF7 
               
               
                 2 
                 ENSG00000116001 
                 TIA1 
               
               
                 2 
                 ENSG00000116350 
                 SRSF4 
               
               
                 2 
                 ENSG00000116497 
                 S100PBP 
               
               
                 2 
                 ENSG00000116560 
                 SFPQ 
               
               
                 2 
                 ENSG00000116580 
                 GON4L 
               
               
                 2 
                 ENSG00000116584 
                 ARHGEF2 
               
               
                 2 
                 ENSG00000116754 
                 SRSF11 
               
               
                 2 
                 ENSG00000116883 
               
               
                 2 
                 ENSG00000117360 
                 PRPF3 
               
               
                 2 
                 ENSG00000117569 
                 PTBP2 
               
               
                 2 
                 ENSG00000117616 
                 C1orf63 
               
               
                 2 
                 ENSG00000117862 
                 TXNDC12 
               
               
                 2 
                 ENSG00000118482 
                 PHF3 
               
               
                 2 
                 ENSG00000118557 
                 PMFBP1 
               
               
                 2 
                 ENSG00000119707 
                 RBM25 
               
               
                 2 
                 ENSG00000119906 
                 FAM178A 
               
               
                 2 
                 ENSG00000120049 
                 KCNIP2 
               
               
                 2 
                 ENSG00000120458 
                 MSANTD2 
               
               
                 2 
                 ENSG00000120662 
                 MTRF1 
               
               
                 2 
                 ENSG00000120798 
                 NR2C1 
               
               
                 2 
                 ENSG00000120832 
                 MTERFD3 
               
               
                 2 
                 ENSG00000121274 
                 PAPD5 
               
               
                 2 
                 ENSG00000121310 
                 ECHDC2 
               
               
                 2 
                 ENSG00000121454 
                 LHX4 
               
               
                 2 
                 ENSG00000121716 
                 PILRB 
               
               
                 2 
                 ENSG00000122085 
                 MTERFD2 
               
               
                 2 
                 ENSG00000122257 
                 RBBP6 
               
               
                 2 
                 ENSG00000122678 
                 POLM 
               
               
                 2 
                 ENSG00000122965 
                 RBM19 
               
               
                 2 
                 ENSG00000124098 
                 FAM210B 
               
               
                 2 
                 ENSG00000124160 
                 NCOA5 
               
               
                 2 
                 ENSG00000124193 
                 SRSF6 
               
               
                 2 
                 ENSG00000124222 
                 STX16 
               
               
                 2 
                 ENSG00000124593 
                 PRICKLE4 
               
               
                 2 
                 ENSG00000124743 
                 KLHL31 
               
               
                 2 
                 ENSG00000125447 
                 GGA3 
               
               
                 2 
                 ENSG00000125633 
                 CCDC93 
               
               
                 2 
                 ENSG00000125814 
                 NAPB 
               
               
                 2 
                 ENSG00000125818 
                 PSMF1 
               
               
                 2 
                 ENSG00000125846 
                 ZNF133 
               
               
                 2 
                 ENSG00000126070 
                 AGO3 
               
               
                 2 
                 ENSG00000126217 
                 MCF2L 
               
               
                 2 
                 ENSG00000126453 
                 BCL2L12 
               
               
                 2 
                 ENSG00000126456 
                 IRF3 
               
               
                 2 
                 ENSG00000126500 
                 FLRT1 
               
               
                 2 
                 ENSG00000126746 
                 ZNF384 
               
               
                 2 
                 ENSG00000126775 
                 ATG14 
               
               
                 2 
                 ENSG00000127366 
                 TAS2R5 
               
               
                 2 
                 ENSG00000127586 
                 CHTF18 
               
               
                 2 
                 ENSG00000127957 
                 PMS2P3 
               
               
                 2 
                 ENSG00000128000 
                 ZNF780B 
               
               
                 2 
                 ENSG00000128159 
                 TUBGCP6 
               
               
                 2 
                 ENSG00000128563 
                 PRKRIP1 
               
               
                 2 
                 ENSG00000128699 
                 ORMDL1 
               
               
                 2 
                 ENSG00000128915 
                 NARG2 
               
               
                 2 
                 ENSG00000129055 
                 ANAPC13 
               
               
                 2 
                 ENSG00000129351 
                 ILF3 
               
               
                 2 
                 ENSG00000129472 
                 RAB2B 
               
               
                 2 
                 ENSG00000129484 
                 PARP2 
               
               
                 2 
                 ENSG00000129933 
                 MAU2 
               
               
                 2 
                 ENSG00000130254 
                 SAFB2 
               
               
                 2 
                 ENSG00000130653 
                 PNPLA7 
               
               
                 2 
                 ENSG00000130684 
                 ZNF337 
               
               
                 2 
                 ENSG00000130948 
                 HSD17B3 
               
               
                 2 
                 ENSG00000131051 
                 RBM39 
               
               
                 2 
                 ENSG00000131127 
                 ZNF141 
               
               
                 2 
                 ENSG00000131398 
                 KCNC3 
               
               
                 2 
                 ENSG00000131591 
                 C1orf159 
               
               
                 2 
                 ENSG00000131797 
                 CLUHP3 
               
               
                 2 
                 ENSG00000132424 
                 PNISR 
               
               
                 2 
                 ENSG00000132485 
                 ZRANB2 
               
               
                 2 
                 ENSG00000132680 
                 KIAA0907 
               
               
                 2 
                 ENSG00000132780 
                 NASP 
               
               
                 2 
                 ENSG00000132793 
                 LPIN3 
               
               
                 2 
                 ENSG00000132952 
                 USPL1 
               
               
                 2 
                 ENSG00000133318 
                 RTN3 
               
               
                 2 
                 ENSG00000133466 
                 C1QTNF6 
               
               
                 2 
                 ENSG00000133619 
                 KRBA1 
               
               
                 2 
                 ENSG00000133624 
                 ZNF767 
               
               
                 2 
                 ENSG00000133858 
                 ZFC3H1 
               
               
                 2 
                 ENSG00000134186 
                 PRPF38B 
               
               
                 2 
                 ENSG00000134253 
                 TRIM45 
               
               
                 2 
                 ENSG00000134453 
                 RBM17 
               
               
                 2 
                 ENSG00000134744 
                 ZCCHC11 
               
               
                 2 
                 ENSG00000134884 
                 ARGLU1 
               
               
                 2 
                 ENSG00000135164 
                 DMTF1 
               
               
                 2 
                 ENSG00000135407 
                 AVIL 
               
               
                 2 
                 ENSG00000135437 
                 RDH5 
               
               
                 2 
                 ENSG00000135473 
                 PAN2 
               
               
                 2 
                 ENSG00000135637 
                 CCDC142 
               
               
                 2 
                 ENSG00000135740 
                 SLC9A5 
               
               
                 2 
                 ENSG00000135976 
                 ANKRD36 
               
               
                 2 
                 ENSG00000136271 
                 DDX56 
               
               
                 2 
                 ENSG00000136819 
                 C9orf78 
               
               
                 2 
                 ENSG00000137185 
                 ZSCAN9 
               
               
                 2 
                 ENSG00000137343 
                 ATAT1 
               
               
                 2 
                 ENSG00000137504 
                 CREBZF 
               
               
                 2 
                 ENSG00000137776 
                 SLTM 
               
               
                 2 
                 ENSG00000137802 
                 MAPKBP1 
               
               
                 2 
                 ENSG00000137817 
                 PARP6 
               
               
                 2 
                 ENSG00000137822 
                 TUBGCP4 
               
               
                 2 
                 ENSG00000138050 
                 THUMPD2 
               
               
                 2 
                 ENSG00000138109 
                 CYP2C9 
               
               
                 2 
                 ENSG00000138658 
                 C4orf21 
               
               
                 2 
                 ENSG00000138834 
                 MAPK8IP3 
               
               
                 2 
                 ENSG00000139190 
                 VAMP1 
               
               
                 2 
                 ENSG00000139574 
                 NPFF 
               
               
                 2 
                 ENSG00000139631 
                 CSAD 
               
               
                 2 
                 ENSG00000139746 
                 RBM26 
               
               
                 2 
                 ENSG00000139908 
                 TSSK4 
               
               
                 2 
                 ENSG00000140009 
                 ESR2 
               
               
                 2 
                 ENSG00000140181 
                 HERC2P2 
               
               
                 2 
                 ENSG00000140398 
                 NEIL1 
               
               
                 2 
                 ENSG00000140400 
                 MAN2C1 
               
               
                 2 
                 ENSG00000140474 
                 ULK3 
               
               
                 2 
                 ENSG00000140488 
                 CELF6 
               
               
                 2 
                 ENSG00000140983 
                 RHOT2 
               
               
                 2 
                 ENSG00000141068 
                 KSR1 
               
               
                 2 
                 ENSG00000141258 
                 SGSM2 
               
               
                 2 
                 ENSG00000141551 
                 CSNK1D 
               
               
                 2 
                 ENSG00000141564 
                 RPTOR 
               
               
                 2 
                 ENSG00000142102 
                 ATHL1 
               
               
                 2 
                 ENSG00000142166 
                 IFNAR1 
               
               
                 2 
                 ENSG00000142233 
                 NTN5 
               
               
                 2 
                 ENSG00000143178 
                 TBX19 
               
               
                 2 
                 ENSG00000143183 
                 TMCO1 
               
               
                 2 
                 ENSG00000143190 
                 POU2F1 
               
               
                 2 
                 ENSG00000143379 
                 SETDB1 
               
               
                 2 
                 ENSG00000143434 
                 SEMA6C 
               
               
                 2 
                 ENSG00000143442 
                 POGZ 
               
               
                 2 
                 ENSG00000143630 
                 HCN3 
               
               
                 2 
                 ENSG00000144026 
                 ZNF514 
               
               
                 2 
                 ENSG00000144161 
                 ZC3H8 
               
               
                 2 
                 ENSG00000144524 
                 COPS7B 
               
               
                 2 
                 ENSG00000145020 
                 AMT 
               
               
                 2 
                 ENSG00000145029 
                 NICN1 
               
               
                 2 
                 ENSG00000145908 
                 ZNF300 
               
               
                 2 
                 ENSG00000146021 
                 KLHL3 
               
               
                 2 
                 ENSG00000146067 
                 FAM193B 
               
               
                 2 
                 ENSG00000146215 
                 CRIP3 
               
               
                 2 
                 ENSG00000146556 
                 WASH2P 
               
               
                 2 
                 ENSG00000146826 
                 C7orf43 
               
               
                 2 
                 ENSG00000146830 
                 GIGYF1 
               
               
                 2 
                 ENSG00000146963 
                 C7orf55- 
               
               
                   
                   
                 LUC7L2 
               
               
                 2 
                 ENSG00000147118 
                 ZNF182 
               
               
                 2 
                 ENSG00000147121 
                 KRBOX4 
               
               
                 2 
                 ENSG00000147162 
                 OGT 
               
               
                 2 
                 ENSG00000147174 
                 ACRC 
               
               
                 2 
                 ENSG00000147180 
                 ZNF711 
               
               
                 2 
                 ENSG00000147437 
                 GNRH1 
               
               
                 2 
                 ENSG00000147576 
                 ADHFE1 
               
               
                 2 
                 ENSG00000147789 
                 ZNF7 
               
               
                 2 
                 ENSG00000147854 
                 UHRF2 
               
               
                 2 
                 ENSG00000148200 
                 NR6A1 
               
               
                 2 
                 ENSG00000148399 
                 DPH7 
               
               
                 2 
                 ENSG00000149532 
                 CPSF7 
               
               
                 2 
                 ENSG00000151006 
                 PRSS53 
               
               
                 2 
                 ENSG00000151303 
                 AGAP11 
               
               
                 2 
                 ENSG00000151376 
                 ME3 
               
               
                 2 
                 ENSG00000151849 
                 CENPJ 
               
               
                 2 
                 ENSG00000152042 
                 NBPF11 
               
               
                 2 
                 ENSG00000152117 
               
               
                 2 
                 ENSG00000152433 
                 ZNF547 
               
               
                 2 
                 ENSG00000152520 
                 PAN3 
               
               
                 2 
                 ENSG00000152527 
                 PLEKHH2 
               
               
                 2 
                 ENSG00000152795 
                 HNRNPDL 
               
               
                 2 
                 ENSG00000152926 
                 ZNF117 
               
               
                 2 
                 ENSG00000153291 
                 SLC25A27 
               
               
                 2 
                 ENSG00000153666 
                 GOLGA8I 
               
               
                 2 
                 ENSG00000153914 
                 SREK1 
               
               
                 2 
                 ENSG00000154144 
                 TBRG1 
               
               
                 2 
                 ENSG00000154263 
                 ABCA10 
               
               
                 2 
                 ENSG00000154832 
                 CXXC1 
               
               
                 2 
                 ENSG00000155229 
                 MMS19 
               
               
                 2 
                 ENSG00000155256 
                 ZFYVE27 
               
               
                 2 
                 ENSG00000155657 
                 TTN 
               
               
                 2 
                 ENSG00000155903 
                 RASA2 
               
               
                 2 
                 ENSG00000156639 
                 ZFAND3 
               
               
                 2 
                 ENSG00000156642 
                 NPTN 
               
               
                 2 
                 ENSG00000157306 
               
               
                 2 
                 ENSG00000157741 
                 UBN2 
               
               
                 2 
                 ENSG00000157764 
                 BRAF 
               
               
                 2 
                 ENSG00000158286 
                 RNF207 
               
               
                 2 
                 ENSG00000158805 
                 ZNF276 
               
               
                 2 
                 ENSG00000158815 
                 FGF17 
               
               
                 2 
                 ENSG00000159086 
                 PAXBP1 
               
               
                 2 
                 ENSG00000159140 
                 SON 
               
               
                 2 
                 ENSG00000159346 
                 ADIPOR1 
               
               
                 2 
                 ENSG00000159461 
                 AMFR 
               
               
                 2 
                 ENSG00000160072 
                 ATAD3B 
               
               
                 2 
                 ENSG00000160323 
                 ADAMTS13 
               
               
                 2 
                 ENSG00000160781 
                 PAQR6 
               
               
                 2 
                 ENSG00000160828 
                 STAG3L2 
               
               
                 2 
                 ENSG00000160953 
                 MUM1 
               
               
                 2 
                 ENSG00000160961 
                 ZNF333 
               
               
                 2 
                 ENSG00000161265 
                 U2AF1L4 
               
               
                 2 
                 ENSG00000161547 
                 SRSF2 
               
               
                 2 
                 ENSG00000161664 
                 ASB16 
               
               
                 2 
                 ENSG00000161912 
                 ADCY10P1 
               
               
                 2 
                 ENSG00000162086 
                 ZNF75A 
               
               
                 2 
                 ENSG00000162231 
                 NXF1 
               
               
                 2 
                 ENSG00000162408 
                 NOL9 
               
               
                 2 
                 ENSG00000162461 
                 SLC25A34 
               
               
                 2 
                 ENSG00000162526 
                 TSSK3 
               
               
                 2 
                 ENSG00000162572 
                 SCNN1D 
               
               
                 2 
                 ENSG00000162601 
                 MYSM1 
               
               
                 2 
                 ENSG00000162650 
                 ATXN7L2 
               
               
                 2 
                 ENSG00000162735 
                 PEX19 
               
               
                 2 
                 ENSG00000162997 
                 PRORSD1P 
               
               
                 2 
                 ENSG00000163354 
                 DCST2 
               
               
                 2 
                 ENSG00000163660 
                 CCNL1 
               
               
                 2 
                 ENSG00000163714 
                 U2SURP 
               
               
                 2 
                 ENSG00000163728 
                 TTC14 
               
               
                 2 
                 ENSG00000163867 
                 ZMYM6 
               
               
                 2 
                 ENSG00000163945 
                 UVSSA 
               
               
                 2 
                 ENSG00000164048 
                 ZNF589 
               
               
                 2 
                 ENSG00000164073 
                 MFSD8 
               
               
                 2 
                 ENSG00000164074 
                 C4orf29 
               
               
                 2 
                 ENSG00000164241 
                 C5orf63 
               
               
                 2 
                 ENSG00000164406 
                 LEAP2 
               
               
                 2 
                 ENSG00000164548 
                 TRA2A 
               
               
                 2 
                 ENSG00000164877 
                 MICALL2 
               
               
                 2 
                 ENSG00000164879 
                 CA3 
               
               
                 2 
                 ENSG00000165275 
                 TRMT10B 
               
               
                 2 
                 ENSG00000165494 
                 PCF11 
               
               
                 2 
                 ENSG00000165699 
                 TSC1 
               
               
                 2 
                 ENSG00000165792 
                 METTL17 
               
               
                 2 
                 ENSG00000165819 
                 METTL3 
               
               
                 2 
                 ENSG00000166012 
                 TAF1D 
               
               
                 2 
                 ENSG00000166169 
                 POLL 
               
               
                 2 
                 ENSG00000166261 
                 ZNF202 
               
               
                 2 
                 ENSG00000166321 
                 NUDT13 
               
               
                 2 
                 ENSG00000166343 
                 MSS51 
               
               
                 2 
                 ENSG00000166405 
                 RIC3 
               
               
                 2 
                 ENSG00000166432 
                 ZMAT1 
               
               
                 2 
                 ENSG00000166436 
                 TRIM66 
               
               
                 2 
                 ENSG00000166667 
                 SPDYE6 
               
               
                 2 
                 ENSG00000166762 
                 CATSPER2 
               
               
                 2 
                 ENSG00000166801 
                 FAM111A 
               
               
                 2 
                 ENSG00000166887 
                 VPS39 
               
               
                 2 
                 ENSG00000167280 
                 ENGASE 
               
               
                 2 
                 ENSG00000167302 
                 ENTHD2 
               
               
                 2 
                 ENSG00000167371 
                 PRRT2 
               
               
                 2 
                 ENSG00000167380 
                 ZNF226 
               
               
                 2 
                 ENSG00000167524 
               
               
                 2 
                 ENSG00000167549 
                 CORO6 
               
               
                 2 
                 ENSG00000167566 
                 NCKAP5L 
               
               
                 2 
                 ENSG00000167615 
                 LENG8 
               
               
                 2 
                 ENSG00000167674 
               
               
                 2 
                 ENSG00000167702 
                 KIFC2 
               
               
                 2 
                 ENSG00000167766 
                 ZNF83 
               
               
                 2 
                 ENSG00000167978 
                 SRRM2 
               
               
                 2 
                 ENSG00000168005 
                 C11orf84 
               
               
                 2 
                 ENSG00000168010 
                 ATG16L2 
               
               
                 2 
                 ENSG00000168066 
                 SF1 
               
               
                 2 
                 ENSG00000168096 
                 ANKS3 
               
               
                 2 
                 ENSG00000168137 
                 SETD5 
               
               
                 2 
                 ENSG00000168310 
                 IRF2 
               
               
                 2 
                 ENSG00000168395 
                 ING5 
               
               
                 2 
                 ENSG00000168566 
                 SNRNP48 
               
               
                 2 
                 ENSG00000168614 
                 NBPF9 
               
               
                 2 
                 ENSG00000168876 
                 ANKRD49 
               
               
                 2 
                 ENSG00000168887 
                 C2orf68 
               
               
                 2 
                 ENSG00000168939 
                 SPRY3 
               
               
                 2 
                 ENSG00000168970 
                 JMJD7- 
               
               
                   
                   
                 PLA2G4B 
               
               
                 2 
                 ENSG00000169045 
                 HNRNPH1 
               
               
                 2 
                 ENSG00000169131 
                 ZNF354A 
               
               
                 2 
                 ENSG00000169203 
               
               
                 2 
                 ENSG00000169246 
                 NPIPB3 
               
               
                 2 
                 ENSG00000169592 
                 INO80E 
               
               
                 2 
                 ENSG00000169660 
                 HEXDC 
               
               
                 2 
                 ENSG00000169885 
                 CALML6 
               
               
                 2 
                 ENSG00000169914 
                 OTUD3 
               
               
                 2 
                 ENSG00000170049 
                 KCNAB3 
               
               
                 2 
                 ENSG00000170074 
                 FAM153A 
               
               
                 2 
                 ENSG00000170234 
                 PWWP2A 
               
               
                 2 
                 ENSG00000170581 
                 STAT2 
               
               
                 2 
                 ENSG00000170919 
                 TPT1-AS1 
               
               
                 2 
                 ENSG00000170949 
                 ZNF160 
               
               
                 2 
                 ENSG00000171163 
                 ZNF692 
               
               
                 2 
                 ENSG00000171456 
                 ASXL1 
               
               
                 2 
                 ENSG00000171824 
                 EXOSC10 
               
               
                 2 
                 ENSG00000172273 
                 HINFP 
               
               
                 2 
                 ENSG00000172345 
                 STARD5 
               
               
                 2 
                 ENSG00000172354 
                 GNB2 
               
               
                 2 
                 ENSG00000172650 
                 AGAP5 
               
               
                 2 
                 ENSG00000172732 
                 MUS81 
               
               
                 2 
                 ENSG00000172803 
                 SNX32 
               
               
                 2 
                 ENSG00000172890 
                 NADSYN1 
               
               
                 2 
                 ENSG00000173064 
                 HECTD4 
               
               
                 2 
                 ENSG00000173209 
                 AHSA2 
               
               
                 2 
                 ENSG00000173275 
                 ZNF449 
               
               
                 2 
                 ENSG00000173531 
                 MST1 
               
               
                 2 
                 ENSG00000173575 
                 CHD2 
               
               
                 2 
                 ENSG00000173681 
                 CXorf23 
               
               
                 2 
                 ENSG00000173991 
                 TCAP 
               
               
                 2 
                 ENSG00000174093 
               
               
                 2 
                 ENSG00000174194 
                 AGAP8 
               
               
                 2 
                 ENSG00000174353 
                 STAG3L3 
               
               
                 2 
                 ENSG00000174652 
                 ZNF266 
               
               
                 2 
                 ENSG00000175066 
                 GK5 
               
               
                 2 
                 ENSG00000175265 
                 GOLGA8A 
               
               
                 2 
                 ENSG00000175309 
                 PHYKPL 
               
               
                 2 
                 ENSG00000175322 
                 ZNF519 
               
               
                 2 
                 ENSG00000175455 
                 CCDC14 
               
               
                 2 
                 ENSG00000175787 
                 ZNF169 
               
               
                 2 
                 ENSG00000176444 
                 CLK2 
               
               
                 2 
                 ENSG00000176681 
                 LRRC37A 
               
               
                 2 
                 ENSG00000176946 
                 THAP4 
               
               
                 2 
                 ENSG00000177042 
                 TMEM80 
               
               
                 2 
                 ENSG00000177202 
                 SPACA4 
               
               
                 2 
                 ENSG00000177225 
                 PDDC1 
               
               
                 2 
                 ENSG00000177479 
                 ARIH2 
               
               
                 2 
                 ENSG00000177485 
                 ZBTB33 
               
               
                 2 
                 ENSG00000177595 
                 PIDD 
               
               
                 2 
                 ENSG00000177853 
                 ZNF518A 
               
               
                 2 
                 ENSG00000177943 
                 MAMDC4 
               
               
                 2 
                 ENSG00000178028 
                 DMAP1 
               
               
                 2 
                 ENSG00000178038 
                 ALS2CL 
               
               
                 2 
                 ENSG00000178188 
                 SH2B1 
               
               
                 2 
                 ENSG00000178252 
                 WDR6 
               
               
                 2 
                 ENSG00000178338 
                 ZNF354B 
               
               
                 2 
                 ENSG00000178397 
                 FAM220A 
               
               
                 2 
                 ENSG00000178567 
                 EPM2AIP1 
               
               
                 2 
                 ENSG00000178761 
                 FAM219B 
               
               
                 2 
                 ENSG00000179304 
                 FAM156B 
               
               
                 2 
                 ENSG00000179406 
                 LINC00174 
               
               
                 2 
                 ENSG00000179979 
                 CRIPAK 
               
               
                 2 
                 ENSG00000180113 
                 TDRD6 
               
               
                 2 
                 ENSG00000180855 
                 ZNF443 
               
               
                 2 
                 ENSG00000180902 
                 D2HGDH 
               
               
                 2 
                 ENSG00000181045 
                 SLC26A11 
               
               
                 2 
                 ENSG00000181523 
                 SGSH 
               
               
                 2 
                 ENSG00000181852 
                 RNF41 
               
               
                 2 
                 ENSG00000182230 
                 FAM153B 
               
               
                 2 
                 ENSG00000182308 
                 DCAF4L1 
               
               
                 2 
                 ENSG00000182310 
                 SPACA6P 
               
               
                 2 
                 ENSG00000182324 
                 KCNJ14 
               
               
                 2 
                 ENSG00000182378 
                 PLCXD1 
               
               
                 2 
                 ENSG00000182473 
                 EXOC7 
               
               
                 2 
                 ENSG00000182484 
                 WASH6P 
               
               
                 2 
                 ENSG00000182646 
                 FAM156A 
               
               
                 2 
                 ENSG00000182685 
                 BRICD5 
               
               
                 2 
                 ENSG00000182796 
                 TMEM198B 
               
               
                 2 
                 ENSG00000182841 
                 RRP7B 
               
               
                 2 
                 ENSG00000182873 
               
               
                 2 
                 ENSG00000182944 
                 EWSR1 
               
               
                 2 
                 ENSG00000182983 
                 ZNF662 
               
               
                 2 
                 ENSG00000182986 
                 ZNF320 
               
               
                 2 
                 ENSG00000183281 
                 PLGLB1 
               
               
                 2 
                 ENSG00000183291 
               
               
                 2 
                 ENSG00000183423 
                 LRIT3 
               
               
                 2 
                 ENSG00000183718 
                 TRIM52 
               
               
                 2 
                 ENSG00000184343 
                 SRPK3 
               
               
                 2 
                 ENSG00000184402 
                 SS18L1 
               
               
                 2 
                 ENSG00000184441 
               
               
                 2 
                 ENSG00000184465 
                 WDR27 
               
               
                 2 
                 ENSG00000184634 
                 MED12 
               
               
                 2 
                 ENSG00000184640 
                 9-Sep 
               
               
                 2 
                 ENSG00000184677 
                 ZBTB40 
               
               
                 2 
                 ENSG00000184787 
                 UBE2G2 
               
               
                 2 
                 ENSG00000184863 
                 RBM33 
               
               
                 2 
                 ENSG00000184925 
                 LCN12 
               
               
                 2 
                 ENSG00000185101 
                 ANO9 
               
               
                 2 
                 ENSG00000185122 
                 HSF1 
               
               
                 2 
                 ENSG00000185128 
                 TBC1D3F 
               
               
                 2 
                 ENSG00000185189 
                 NRBP2 
               
               
                 2 
                 ENSG00000185219 
                 ZNF445 
               
               
                 2 
                 ENSG00000185246 
                 PRPF39 
               
               
                 2 
                 ENSG00000185324 
                 CDK10 
               
               
                 2 
                 ENSG00000185485 
                 SDHAP1 
               
               
                 2 
                 ENSG00000185596 
                 WASH3P 
               
               
                 2 
                 ENSG00000185684 
                 EP400NL 
               
               
                 2 
                 ENSG00000185829 
                 ARL17A 
               
               
                 2 
                 ENSG00000185842 
                 DNAH14 
               
               
                 2 
                 ENSG00000185864 
                 NPIPB4 
               
               
                 2 
                 ENSG00000185946 
                 RNPC3 
               
               
                 2 
                 ENSG00000185986 
                 SDHAP3 
               
               
                 2 
                 ENSG00000186088 
                 GSAP 
               
               
                 2 
                 ENSG00000186166 
                 CCDC84 
               
               
                 2 
                 ENSG00000186204 
                 CYP4F12 
               
               
                 2 
                 ENSG00000186275 
                 NBPF12 
               
               
                 2 
                 ENSG00000186283 
                 TOR3A 
               
               
                 2 
                 ENSG00000186301 
                 MST1P2 
               
               
                 2 
                 ENSG00000186376 
                 ZNF75D 
               
               
                 2 
                 ENSG00000186566 
                 GPATCH8 
               
               
                 2 
                 ENSG00000186567 
                 CEACAM19 
               
               
                 2 
                 ENSG00000186715 
                 MST1L 
               
               
                 2 
                 ENSG00000186812 
                 ZNF397 
               
               
                 2 
                 ENSG00000186814 
                 ZSCAN30 
               
               
                 2 
                 ENSG00000186834 
                 HEXIM1 
               
               
                 2 
                 ENSG00000186908 
                 ZDHHC17 
               
               
                 2 
                 ENSG00000187066 
                 TMEM262 
               
               
                 2 
                 ENSG00000187961 
                 KLHL17 
               
               
                 2 
                 ENSG00000188206 
                 HNRNPU-AS1 
               
               
                 2 
                 ENSG00000188227 
                 ZNF793 
               
               
                 2 
                 ENSG00000188234 
                 AGAP4 
               
               
                 2 
                 ENSG00000188428 
                 BLOC1S5 
               
               
                 2 
                 ENSG00000188529 
                 SRSF10 
               
               
                 2 
                 ENSG00000188554 
                 NBR1 
               
               
                 2 
                 ENSG00000188738 
                 FSIP2 
               
               
                 2 
                 ENSG00000188811 
                 NHLRC3 
               
               
                 2 
                 ENSG00000188827 
                 SLX4 
               
               
                 2 
                 ENSG00000189007 
                 ADAT2 
               
               
                 2 
                 ENSG00000189136 
                 UBE2Q2P1 
               
               
                 2 
                 ENSG00000196074 
                 SYCP2 
               
               
                 2 
                 ENSG00000196123 
                 KIAA0895L 
               
               
                 2 
                 ENSG00000196295 
               
               
                 2 
                 ENSG00000196296 
                 ATP2A1 
               
               
                 2 
                 ENSG00000196387 
                 ZNF140 
               
               
                 2 
                 ENSG00000196409 
                 ZNF658 
               
               
                 2 
                 ENSG00000196440 
                 ARMCX4 
               
               
                 2 
                 ENSG00000196644 
                 GPR89C 
               
               
                 2 
                 ENSG00000196648 
                 GOLGA6L20 
               
               
                 2 
                 ENSG00000196670 
                 ZFP62 
               
               
                 2 
                 ENSG00000196689 
                 TRPV1 
               
               
                 2 
                 ENSG00000196696 
                 PDXDC2P 
               
               
                 2 
                 ENSG00000196757 
                 ZNF700 
               
               
                 2 
                 ENSG00000196912 
                 ANKRD36B 
               
               
                 2 
                 ENSG00000197119 
                 SLC25A29 
               
               
                 2 
                 ENSG00000197124 
                 ZNF682 
               
               
                 2 
                 ENSG00000197162 
                 ZNF785 
               
               
                 2 
                 ENSG00000197182 
               
               
                 2 
                 ENSG00000197343 
                 ZNF655 
               
               
                 2 
                 ENSG00000197558 
                 SSPO 
               
               
                 2 
                 ENSG00000197608 
                 ZNF841 
               
               
                 2 
                 ENSG00000197681 
                 TBC1D3 
               
               
                 2 
                 ENSG00000197774 
                 EME2 
               
               
                 2 
                 ENSG00000197857 
                 ZNF44 
               
               
                 2 
                 ENSG00000197948 
                 FCHSD1 
               
               
                 2 
                 ENSG00000197961 
                 ZNF121 
               
               
                 2 
                 ENSG00000197976 
                 AKAP17A 
               
               
                 2 
                 ENSG00000197989 
                 SNHG12 
               
               
                 2 
                 ENSG00000198035 
                 AGAP9 
               
               
                 2 
                 ENSG00000198040 
                 ZNF84 
               
               
                 2 
                 ENSG00000198064 
               
               
                 2 
                 ENSG00000198105 
                 ZNF248 
               
               
                 2 
                 ENSG00000198150 
               
               
                 2 
                 ENSG00000198198 
                 SZT2 
               
               
                 2 
                 ENSG00000198231 
                 DDX42 
               
               
                 2 
                 ENSG00000198276 
                 UCKL1 
               
               
                 2 
                 ENSG00000198393 
                 ZNF26 
               
               
                 2 
                 ENSG00000198556 
                 ZNF789 
               
               
                 2 
                 ENSG00000198563 
                 DDX39B 
               
               
                 2 
                 ENSG00000198590 
                 C3orf35 
               
               
                 2 
                 ENSG00000198625 
                 MDM4 
               
               
                 2 
                 ENSG00000198799 
                 LRIG2 
               
               
                 2 
                 ENSG00000203392 
               
               
                 2 
                 ENSG00000203667 
                 COX20 
               
               
                 2 
                 ENSG00000203709 
                 C1orf132 
               
               
                 2 
                 ENSG00000203761 
                 MSTO2P 
               
               
                 2 
                 ENSG00000203815 
                 FAM231D 
               
               
                 2 
                 ENSG00000203880 
                 PCMTD2 
               
               
                 2 
                 ENSG00000204149 
                 AGAP6 
               
               
                 2 
                 ENSG00000204164 
                 BMS1P5 
               
               
                 2 
                 ENSG00000204271 
                 SPIN3 
               
               
                 2 
                 ENSG00000204305 
                 AGER 
               
               
                 2 
                 ENSG00000204311 
                 DFNB59 
               
               
                 2 
                 ENSG00000204348 
                 DXO 
               
               
                 2 
                 ENSG00000204351 
                 SKIV2L 
               
               
                 2 
                 ENSG00000204410 
                 MSH5 
               
               
                 2 
                 ENSG00000204514 
                 ZNF814 
               
               
                 2 
                 ENSG00000204576 
                 PRR3 
               
               
                 2 
                 ENSG00000204681 
                 GABBR1 
               
               
                 2 
                 ENSG00000204946 
                 ZNF783 
               
               
                 2 
                 ENSG00000205047 
               
               
                 2 
                 ENSG00000205085 
                 FAM71F2 
               
               
                 2 
                 ENSG00000205238 
                 SPDYE2 
               
               
                 2 
                 ENSG00000205307 
                 SAP25 
               
               
                 2 
                 ENSG00000205560 
                 CPT1B 
               
               
                 2 
                 ENSG00000205583 
                 STAG3L1 
               
               
                 2 
                 ENSG00000205885 
                 C1RL-AS1 
               
               
                 2 
                 ENSG00000205890 
               
               
                 2 
                 ENSG00000205923 
                 CEMP1 
               
               
                 2 
                 ENSG00000205959 
               
               
                 2 
                 ENSG00000206149 
                 HERC2P9 
               
               
                 2 
                 ENSG00000206417 
                 H1FX-AS1 
               
               
                 2 
                 ENSG00000206573 
                 SETD5-AS1 
               
               
                 2 
                 ENSG00000211454 
                 AKR7L 
               
               
                 2 
                 ENSG00000212123 
                 PRR22 
               
               
                 2 
                 ENSG00000212127 
                 TAS2R14 
               
               
                 2 
                 ENSG00000212694 
               
               
                 2 
                 ENSG00000213139 
                 CRYGS 
               
               
                 2 
                 ENSG00000213190 
                 MLLT11 
               
               
                 2 
                 ENSG00000213246 
                 SUPT4H1 
               
               
                 2 
                 ENSG00000213339 
                 QTRT1 
               
               
                 2 
                 ENSG00000213347 
                 MXD3 
               
               
                 2 
                 ENSG00000213443 
               
               
                 2 
                 ENSG00000213599 
                 SLX1A- 
               
               
                   
                   
                 SULT1A3 
               
               
                 2 
                 ENSG00000213901 
                 SLC23A3 
               
               
                 2 
                 ENSG00000213918 
                 DNASE1 
               
               
                 2 
                 ENSG00000213983 
                 AP1G2 
               
               
                 2 
                 ENSG00000213999 
                 MEF2B 
               
               
                 2 
                 ENSG00000214021 
                 TTLL3 
               
               
                 2 
                 ENSG00000214135 
               
               
                 2 
                 ENSG00000214176 
                 PLEKHM1P 
               
               
                 2 
                 ENSG00000214279 
               
               
                 2 
                 ENSG00000214331 
               
               
                 2 
                 ENSG00000214455 
                 RCN1P2 
               
               
                 2 
                 ENSG00000214756 
                 METTL12 
               
               
                 2 
                 ENSG00000214765 
                 SEPT7P2 
               
               
                 2 
                 ENSG00000214783 
                 POLR2J4 
               
               
                 2 
                 ENSG00000214826 
                 DDX12P 
               
               
                 2 
                 ENSG00000214827 
                 MTCP1 
               
               
                 2 
                 ENSG00000215022 
               
               
                 2 
                 ENSG00000215041 
                 NEURL4 
               
               
                 2 
                 ENSG00000215126 
                 CBWD7 
               
               
                 2 
                 ENSG00000215158 
               
               
                 2 
                 ENSG00000215252 
                 GOLGA8B 
               
               
                 2 
                 ENSG00000215298 
               
               
                 2 
                 ENSG00000215375 
                 MYL5 
               
               
                 2 
                 ENSG00000215417 
                 MIR17HG 
               
               
                 2 
                 ENSG00000215424 
                 MCM3AP- 
               
               
                   
                   
                 AS1 
               
               
                 2 
                 ENSG00000215440 
                 NPEPL1 
               
               
                 2 
                 ENSG00000215513 
                 PI4KAP1 
               
               
                 2 
                 ENSG00000215769 
               
               
                 2 
                 ENSG00000215788 
                 TNFRSF25 
               
               
                 2 
                 ENSG00000216937 
                 CCDC7 
               
               
                 2 
                 ENSG00000218891 
                 ZNF579 
               
               
                 2 
                 ENSG00000220201 
                 ZGLP1 
               
               
                 2 
                 ENSG00000221944 
                 TIGD1 
               
               
                 2 
                 ENSG00000221978 
                 CCNL2 
               
               
                 2 
                 ENSG00000223509 
               
               
                 2 
                 ENSG00000223705 
                 NSUN5P1 
               
               
                 2 
                 ENSG00000223745 
               
               
                 2 
                 ENSG00000223839 
                 FAM95B1 
               
               
                 2 
                 ENSG00000223959 
                 AFG3L1P 
               
               
                 2 
                 ENSG00000224186 
                 C5orf66 
               
               
                 2 
                 ENSG00000224660 
                 SH3BP5-AS1 
               
               
                 2 
                 ENSG00000224956 
               
               
                 2 
                 ENSG00000224975 
                 INE1 
               
               
                 2 
                 ENSG00000225032 
               
               
                 2 
                 ENSG00000225138 
               
               
                 2 
                 ENSG00000225313 
               
               
                 2 
                 ENSG00000225373 
                 WASH5P 
               
               
                 2 
                 ENSG00000225697 
                 SLC26A6 
               
               
                 2 
                 ENSG00000225828 
                 FAM229A 
               
               
                 2 
                 ENSG00000225855 
                 RUSC1-AS1 
               
               
                 2 
                 ENSG00000225892 
               
               
                 2 
                 ENSG00000226232 
               
               
                 2 
                 ENSG00000226332 
               
               
                 2 
                 ENSG00000226696 
                 LENG8-AS1 
               
               
                 2 
                 ENSG00000226763 
                 SRRM5 
               
               
                 2 
                 ENSG00000227232 
                 WASH7P 
               
               
                 2 
                 ENSG00000227543 
                 SPAG5-AS1 
               
               
                 2 
                 ENSG00000227671 
                 MIR3916 
               
               
                 2 
                 ENSG00000227896 
               
               
                 2 
                 ENSG00000228274 
               
               
                 2 
                 ENSG00000228315 
                 GUSBP11 
               
               
                 2 
                 ENSG00000228393 
                 LINC01004 
               
               
                 2 
                 ENSG00000228409 
                 CCT6P1 
               
               
                 2 
                 ENSG00000228492 
                 RAB11FIP1P1 
               
               
                 2 
                 ENSG00000228784 
                 LINC00954 
               
               
                 2 
                 ENSG00000229180 
               
               
                 2 
                 ENSG00000229186 
                 ADAM1A 
               
               
                 2 
                 ENSG00000230124 
               
               
                 2 
                 ENSG00000230373 
                 GOLGA6L5P 
               
               
                 2 
                 ENSG00000230454 
               
               
                 2 
                 ENSG00000230551 
               
               
                 2 
                 ENSG00000230606 
               
               
                 2 
                 ENSG00000230715 
               
               
                 2 
                 ENSG00000232807 
               
               
                 2 
                 ENSG00000233137 
               
               
                 2 
                 ENSG00000233175 
               
               
                 2 
                 ENSG00000233184 
               
               
                 2 
                 ENSG00000234072 
               
               
                 2 
                 ENSG00000234290 
               
               
                 2 
                 ENSG00000234353 
               
               
                 2 
                 ENSG00000234420 
                 ZNF37BP 
               
               
                 2 
                 ENSG00000234585 
                 CCT6P3 
               
               
                 2 
                 ENSG00000234616 
                 JRK 
               
               
                 2 
                 ENSG00000234631 
               
               
                 2 
                 ENSG00000234769 
                 WASH4P 
               
               
                 2 
                 ENSG00000234771 
               
               
                 2 
                 ENSG00000234912 
                 LINC00338 
               
               
                 2 
                 ENSG00000235016 
               
               
                 2 
                 ENSG00000235194 
                 PPP1R3E 
               
               
                 2 
                 ENSG00000235381 
               
               
                 2 
                 ENSG00000235703 
                 LINC00894 
               
               
                 2 
                 ENSG00000235999 
               
               
                 2 
                 ENSG00000236017 
                 ASMTL-AS1 
               
               
                 2 
                 ENSG00000236088 
                 COX10-AS1 
               
               
                 2 
                 ENSG00000236144 
               
               
                 2 
                 ENSG00000236255 
               
               
                 2 
                 ENSG00000236287 
                 ZBED5 
               
               
                 2 
                 ENSG00000236438 
                 FAM157A 
               
               
                 2 
                 ENSG00000237298 
                 TTN-AS1 
               
               
                 2 
                 ENSG00000237441 
                 RGL2 
               
               
                 2 
                 ENSG00000237491 
               
               
                 2 
                 ENSG00000238083 
                 LRRC37A2 
               
               
                 2 
                 ENSG00000239382 
                 ALKBH6 
               
               
                 2 
                 ENSG00000239665 
               
               
                 2 
                 ENSG00000240038 
                 AMY2B 
               
               
                 2 
                 ENSG00000240053 
                 LY6G5B 
               
               
                 2 
                 ENSG00000240288 
                 GHRLOS 
               
               
                 2 
                 ENSG00000240291 
               
               
                 2 
                 ENSG00000240731 
               
               
                 2 
                 ENSG00000241014 
               
               
                 2 
                 ENSG00000241058 
                 NSUN6 
               
               
                 2 
                 ENSG00000241404 
                 EGFL8 
               
               
                 2 
                 ENSG00000241489 
               
               
                 2 
                 ENSG00000241528 
               
               
                 2 
                 ENSG00000241769 
                 LINC00893 
               
               
                 2 
                 ENSG00000242028 
                 HYPK 
               
               
                 2 
                 ENSG00000242125 
                 SNHG3 
               
               
                 2 
                 ENSG00000242282 
               
               
                 2 
                 ENSG00000242384 
                 TBC1D3H 
               
               
                 2 
                 ENSG00000242802 
                 AP5Z1 
               
               
                 2 
                 ENSG00000242861 
               
               
                 2 
                 ENSG00000242866 
                 STRC 
               
               
                 2 
                 ENSG00000243155 
               
               
                 2 
                 ENSG00000243302 
               
               
                 2 
                 ENSG00000243452 
                 NBPF15 
               
               
                 2 
                 ENSG00000243679 
               
               
                 2 
                 ENSG00000243708 
                 PLA2G4B 
               
               
                 2 
                 ENSG00000243716 
                 NPIPB5 
               
               
                 2 
                 ENSG00000244119 
                 PDCL3P4 
               
               
                 2 
                 ENSG00000244151 
               
               
                 2 
                 ENSG00000244480 
               
               
                 2 
                 ENSG00000244560 
               
               
                 2 
                 ENSG00000244754 
                 N4BP2L2 
               
               
                 2 
                 ENSG00000244879 
                 GABPB1-AS1 
               
               
                 2 
                 ENSG00000245149 
                 RNF139-AS1 
               
               
                 2 
                 ENSG00000245532 
                 NEAT1 
               
               
                 2 
                 ENSG00000245849 
                 RAD51-AS1 
               
               
                 2 
                 ENSG00000245970 
               
               
                 2 
                 ENSG00000246090 
               
               
                 2 
                 ENSG00000246339 
                 EXTL3-AS1 
               
               
                 2 
                 ENSG00000246451 
               
               
                 2 
                 ENSG00000246922 
                 UBAP1L 
               
               
                 2 
                 ENSG00000247679 
               
               
                 2 
                 ENSG00000248019 
                 FAM13A-AS1 
               
               
                 2 
                 ENSG00000248124 
                 RRN3P1 
               
               
                 2 
                 ENSG00000249087 
                 C1orf213 
               
               
                 2 
                 ENSG00000250067 
                 YJEFN3 
               
               
                 2 
                 ENSG00000250506 
                 CDK3 
               
               
                 2 
                 ENSG00000251022 
                 THAP9-AS1 
               
               
                 2 
                 ENSG00000251136 
               
               
                 2 
                 ENSG00000251247 
                 ZNF345 
               
               
                 2 
                 ENSG00000251364 
               
               
                 2 
                 ENSG00000251369 
                 ZNF550 
               
               
                 2 
                 ENSG00000251432 
               
               
                 2 
                 ENSG00000251562 
                 MALAT1 
               
               
                 2 
                 ENSG00000252690 
                 SCARNA15 
               
               
                 2 
                 ENSG00000253106 
               
               
                 2 
                 ENSG00000253200 
               
               
                 2 
                 ENSG00000253352 
                 TUG1 
               
               
                 2 
                 ENSG00000254363 
               
               
                 2 
                 ENSG00000254413 
                 CHKB-CPT1B 
               
               
                 2 
                 ENSG00000254815 
               
               
                 2 
                 ENSG00000254995 
                 STX16- 
               
               
                   
                   
                 NPEPL1 
               
               
                 2 
                 ENSG00000255031 
               
               
                 2 
                 ENSG00000255182 
               
               
                 2 
                 ENSG00000255717 
                 SNHG1 
               
               
                 2 
                 ENSG00000256028 
               
               
                 2 
                 ENSG00000256223 
                 ZNF10 
               
               
                 2 
                 ENSG00000256294 
                 ZNF225 
               
               
                 2 
                 ENSG00000256525 
                 POLG2 
               
               
                 2 
                 ENSG00000256667 
                 KLRAP1 
               
               
                 2 
                 ENSG00000257511 
               
               
                 2 
                 ENSG00000257621 
               
               
                 2 
                 ENSG00000258297 
               
               
                 2 
                 ENSG00000258311 
               
               
                 2 
                 ENSG00000258441 
                 LINC00641 
               
               
                 2 
                 ENSG00000258461 
               
               
                 2 
                 ENSG00000258472 
               
               
                 2 
                 ENSG00000258634 
               
               
                 2 
                 ENSG00000258727 
               
               
                 2 
                 ENSG00000258839 
                 MC1R 
               
               
                 2 
                 ENSG00000258890 
                 CEP95 
               
               
                 2 
                 ENSG00000259820 
               
               
                 2 
                 ENSG00000259865 
               
               
                 2 
                 ENSG00000259891 
               
               
                 2 
                 ENSG00000259972 
               
               
                 2 
                 ENSG00000259994 
               
               
                 2 
                 ENSG00000260091 
               
               
                 2 
                 ENSG00000260236 
               
               
                 2 
                 ENSG00000260257 
               
               
                 2 
                 ENSG00000260296 
               
               
                 2 
                 ENSG00000260306 
               
               
                 2 
                 ENSG00000260565 
                 ERVK13-1 
               
               
                 2 
                 ENSG00000260669 
               
               
                 2 
                 ENSG00000260711 
               
               
                 2 
                 ENSG00000260729 
               
               
                 2 
                 ENSG00000260772 
               
               
                 2 
                 ENSG00000260778 
                 MIR940 
               
               
                 2 
                 ENSG00000260837 
               
               
                 2 
                 ENSG00000260872 
               
               
                 2 
                 ENSG00000260917 
               
               
                 2 
                 ENSG00000260924 
               
               
                 2 
                 ENSG00000260942 
                 CAPN10-AS1 
               
               
                 2 
                 ENSG00000261015 
               
               
                 2 
                 ENSG00000261052 
                 SULT1A3 
               
               
                 2 
                 ENSG00000261067 
               
               
                 2 
                 ENSG00000261087 
               
               
                 2 
                 ENSG00000261136 
               
               
                 2 
                 ENSG00000261139 
               
               
                 2 
                 ENSG00000261254 
               
               
                 2 
                 ENSG00000261286 
               
               
                 2 
                 ENSG00000261324 
               
               
                 2 
                 ENSG00000261326 
               
               
                 2 
                 ENSG00000261355 
               
               
                 2 
                 ENSG00000261408 
                 TEN1-CDK3 
               
               
                 2 
                 ENSG00000261460 
               
               
                 2 
                 ENSG00000261488 
               
               
                 2 
                 ENSG00000261490 
               
               
                 2 
                 ENSG00000261505 
               
               
                 2 
                 ENSG00000261526 
               
               
                 2 
                 ENSG00000261556 
               
               
                 2 
                 ENSG00000261584 
               
               
                 2 
                 ENSG00000261613 
               
               
                 2 
                 ENSG00000261799 
               
               
                 2 
                 ENSG00000262580 
               
               
                 2 
                 ENSG00000262877 
               
               
                 2 
                 ENSG00000263020 
               
               
                 2 
                 ENSG00000263126 
               
               
                 2 
                 ENSG00000263198 
               
               
                 2 
                 ENSG00000263272 
               
               
                 2 
                 ENSG00000263276 
               
               
                 2 
                 ENSG00000263327 
                 TAPT1-AS1 
               
               
                 2 
                 ENSG00000264098 
               
               
                 2 
                 ENSG00000264112 
               
               
                 2 
                 ENSG00000264538 
               
               
                 2 
                 ENSG00000264772 
                 SNORA67 
               
               
                 2 
                 ENSG00000265298 
               
               
                 2 
                 ENSG00000265629 
               
               
                 2 
                 ENSG00000265690 
               
               
                 2 
                 ENSG00000266086 
               
               
                 2 
                 ENSG00000266714 
                 MYO15B 
               
               
                 2 
                 ENSG00000267152 
               
               
                 2 
                 ENSG00000267244 
               
               
                 2 
                 ENSG00000267281 
               
               
                 2 
                 ENSG00000267283 
               
               
                 2 
                 ENSG00000267680 
                 ZNF224 
               
               
                 2 
                 ENSG00000267896 
               
               
                 2 
                 ENSG00000267940 
               
               
                 2 
                 ENSG00000268030 
               
               
                 2 
                 ENSG00000268220 
               
               
                 2 
                 ENSG00000268471 
                 MIR4453 
               
               
                 2 
                 ENSG00000269131 
               
               
                 2 
                 ENSG00000269352 
               
               
                 2 
                 ENSG00000269399 
               
               
                 2 
                 ENSG00000269680 
               
               
                 2 
                 ENSG00000269751 
               
               
                 2 
                 ENSG00000269821 
                 KCNQ1OT1 
               
               
                 2 
                 ENSG00000269928 
               
               
                 2 
                 ENSG00000269929 
               
               
                 2 
                 ENSG00000269958 
               
               
                 2 
                 ENSG00000270012 
               
               
                 2 
                 ENSG00000270015 
               
               
                 2 
                 ENSG00000270055 
               
               
                 2 
                 ENSG00000270069 
               
               
                 2 
                 ENSG00000270189 
               
               
                 2 
                 ENSG00000270574 
               
               
                 2 
                 ENSG00000271344 
               
               
                 2 
                 ENSG00000271430 
               
               
                 2 
                 ENSG00000271529 
                 CICP14 
               
               
                 2 
                 ENSG00000271533 
               
               
                 2 
                 ENSG00000271795 
               
               
                 2 
                 ENSG00000271816 
               
               
                 2 
                 ENSG00000271857 
               
               
                 2 
                 ENSG00000271870 
               
               
                 2 
                 ENSG00000271895 
               
               
                 2 
                 ENSG00000271975 
               
               
                 2 
                 ENSG00000271997 
               
               
                 2 
                 ENSG00000272077 
               
               
                 2 
                 ENSG00000272141 
               
               
                 2 
                 ENSG00000272145 
                 NFYC-AS1 
               
               
                 2 
                 ENSG00000272216 
               
               
                 2 
                 ENSG00000272316 
               
               
                 2 
                 ENSG00000272356 
               
               
                 2 
                 ENSG00000272455 
               
               
                 2 
                 ENSG00000272505 
               
               
                 2 
                 ENSG00000272578 
               
               
                 2 
                 ENSG00000272589 
                 ZSWIM8-AS1 
               
               
                 2 
                 ENSG00000272631 
               
               
                 2 
                 ENSG00000272645 
               
               
                 2 
                 ENSG00000272658 
               
               
                 2 
                 ENSG00000272668 
               
               
                 2 
                 ENSG00000272720 
               
               
                 2 
                 ENSG00000272752 
                 STAG3L5P- 
               
               
                   
                   
                 PVRIG2P- 
               
               
                   
                   
                 PILRB 
               
               
                 2 
                 ENSG00000272782 
               
               
                 2 
                 ENSG00000272849 
               
               
                 2 
                 ENSG00000272916 
               
               
                 2 
                 ENSG00000272977 
               
               
                 2 
                 ENSG00000273000 
               
               
                 2 
                 ENSG00000273131 
               
               
                 2 
                 ENSG00000273137 
               
               
                 2 
                 ENSG00000273151 
               
               
                 2 
                 ENSG00000273271 
               
               
                 2 
                 ENSG00000273373 
               
               
                 2 
                 ENSG00000273466 
               
               
                 2 
                 ENSG00000273478 
               
               
                 3 
                 ENSG00000067082 
                 KLF6 
               
               
                 3 
                 ENSG00000108551 
                 RASD1 
               
               
                 3 
                 ENSG00000120129 
                 DUSP1 
               
               
                 3 
                 ENSG00000120738 
                 EGR1 
               
               
                 3 
                 ENSG00000123358 
                 NR4A1 
               
               
                 3 
                 ENSG00000125740 
                 FOSB 
               
               
                 3 
                 ENSG00000128016 
                 ZFP36 
               
               
                 3 
                 ENSG00000128342 
                 LIF 
               
               
                 3 
                 ENSG00000137331 
                 IER3 
               
               
                 3 
                 ENSG00000139318 
                 DUSP6 
               
               
                 3 
                 ENSG00000142178 
                 SIK1 
               
               
                 3 
                 ENSG00000148339 
                 SLC25A25 
               
               
                 3 
                 ENSG00000153234 
                 NR4A2 
               
               
                 3 
                 ENSG00000158050 
                 DUSP2 
               
               
                 3 
                 ENSG00000159388 
                 BTG2 
               
               
                 3 
                 ENSG00000160888 
                 IER2 
               
               
                 3 
                 ENSG00000170345 
                 FOS 
               
               
                 3 
                 ENSG00000171223 
                 JUNB 
               
               
                 3 
                 ENSG00000177606 
                 JUN 
               
               
                 3 
                 ENSG00000198355 
                 PIM3 
               
               
                 4 
                 ENSG00000062582 
                 MRPS24 
               
               
                 4 
                 ENSG00000065518 
                 NDUFB4 
               
               
                 4 
                 ENSG00000090266 
                 NDUFB2 
               
               
                 4 
                 ENSG00000099341 
                 PSMD8 
               
               
                 4 
                 ENSG00000099795 
                 NDUFB7 
               
               
                 4 
                 ENSG00000100216 
                 TOMM22 
               
               
                 4 
                 ENSG00000103363 
                 TCEB2 
               
               
                 4 
                 ENSG00000106153 
                 CHCHD2 
               
               
                 4 
                 ENSG00000110801 
                 PSMD9 
               
               
                 4 
                 ENSG00000111639 
                 MRPL51 
               
               
                 4 
                 ENSG00000111775 
                 COX6A1 
               
               
                 4 
                 ENSG00000112695 
                 COX7A2 
               
               
                 4 
                 ENSG00000116459 
                 ATP5F1 
               
               
                 4 
                 ENSG00000119013 
                 NDUFB3 
               
               
                 4 
                 ENSG00000120509 
                 PDZD11 
               
               
                 4 
                 ENSG00000125356 
                 NDUFA1 
               
               
                 4 
                 ENSG00000125445 
                 MRPS7 
               
               
                 4 
                 ENSG00000125995 
                 ROMO1 
               
               
                 4 
                 ENSG00000126267 
                 COX6B1 
               
               
                 4 
                 ENSG00000126768 
                 TIMM17B 
               
               
                 4 
                 ENSG00000127540 
                 UQCR11 
               
               
                 4 
                 ENSG00000127774 
                 EMC6 
               
               
                 4 
                 ENSG00000131174 
                 COX7B 
               
               
                 4 
                 ENSG00000135441 
                 BLOC1S1 
               
               
                 4 
                 ENSG00000135940 
                 COX5B 
               
               
                 4 
                 ENSG00000136930 
                 PSMB7 
               
               
                 4 
                 ENSG00000140990 
                 NDUFB10 
               
               
                 4 
                 ENSG00000141552 
                 ANAPC11 
               
               
                 4 
                 ENSG00000141759 
                 TXNL4A 
               
               
                 4 
                 ENSG00000143977 
                 SNRPG 
               
               
                 4 
                 ENSG00000145494 
                 NDUFS6 
               
               
                 4 
                 ENSG00000150779 
                 TIMM8B 
               
               
                 4 
                 ENSG00000151366 
                 NDUFC2 
               
               
                 4 
                 ENSG00000155368 
                 DBI 
               
               
                 4 
                 ENSG00000156411 
                 C14orf2 
               
               
                 4 
                 ENSG00000163634 
                 THOC7 
               
               
                 4 
                 ENSG00000164405 
                 UQCRQ 
               
               
                 4 
                 ENSG00000164919 
                 COX6C 
               
               
                 4 
                 ENSG00000165264 
                 NDUFB6 
               
               
                 4 
                 ENSG00000165283 
                 STOML2 
               
               
                 4 
                 ENSG00000166136 
                 NDUFB8 
               
               
                 4 
                 ENSG00000169020 
                 ATP5I 
               
               
                 4 
                 ENSG00000169021 
                 UQCRFS1 
               
               
                 4 
                 ENSG00000171421 
                 MRPL36 
               
               
                 4 
                 ENSG00000172428 
                 MYEOV2 
               
               
                 4 
                 ENSG00000172586 
                 CHCHD1 
               
               
                 4 
                 ENSG00000173436 
                 MINOS1 
               
               
                 4 
                 ENSG00000173915 
                 USMG5 
               
               
                 4 
                 ENSG00000176340 
                 COX8A 
               
               
                 4 
                 ENSG00000177700 
                 POLR2L 
               
               
                 4 
                 ENSG00000178307 
                 TMEM11 
               
               
                 4 
                 ENSG00000178741 
                 COX5A 
               
               
                 4 
                 ENSG00000183617 
                 MRPL54 
               
               
                 4 
                 ENSG00000184076 
                 UQCR10 
               
               
                 4 
                 ENSG00000184752 
                 NDUFA12 
               
               
                 4 
                 ENSG00000185721 
                 DRG1 
               
               
                 4 
                 ENSG00000186010 
                 NDUFA13 
               
               
                 4 
                 ENSG00000188612 
                 SUMO2 
               
               
                 4 
                 ENSG00000189043 
                 NDUFA4 
               
               
                 4 
                 ENSG00000198522 
                 GPN1 
               
               
                 4 
                 ENSG00000204922 
                 C11orf83 
               
               
                 4 
                 ENSG00000213619 
                 NDUFS3 
               
               
                 4 
                 ENSG00000241468 
                 ATP5J2 
               
               
                 4 
                 ENSG00000262814 
                 MRPL12 
               
               
                 5 
                 ENSG00000000460 
                 C1orf112 
               
               
                 5 
                 ENSG00000004142 
                 POLDIP2 
               
               
                 5 
                 ENSG00000006634 
                 DBF4 
               
               
                 5 
                 ENSG00000007968 
                 E2F2 
               
               
                 5 
                 ENSG00000010292 
                 NCAPD2 
               
               
                 5 
                 ENSG00000011426 
                 ANLN 
               
               
                 5 
                 ENSG00000024526 
                 DEPDC1 
               
               
                 5 
                 ENSG00000034063 
                 UHRF1 
               
               
                 5 
                 ENSG00000040275 
                 SPDL1 
               
               
                 5 
                 ENSG00000048140 
                 TSPAN17 
               
               
                 5 
                 ENSG00000049541 
                 RFC2 
               
               
                 5 
                 ENSG00000051180 
                 RAD51 
               
               
                 5 
                 ENSG00000055044 
                 NOP58 
               
               
                 5 
                 ENSG00000066279 
                 ASPM 
               
               
                 5 
                 ENSG00000068489 
                 PRR11 
               
               
                 5 
                 ENSG00000072571 
                 HMMR 
               
               
                 5 
                 ENSG00000075218 
                 GTSE1 
               
               
                 5 
                 ENSG00000075702 
                 WDR62 
               
               
                 5 
                 ENSG00000077152 
                 UBE2T 
               
               
                 5 
                 ENSG00000080986 
                 NDC80 
               
               
                 5 
                 ENSG00000085840 
                 ORC1 
               
               
                 5 
                 ENSG00000085999 
                 RAD54L 
               
               
                 5 
                 ENSG00000087111 
                 PIGS 
               
               
                 5 
                 ENSG00000087586 
                 AURKA 
               
               
                 5 
                 ENSG00000088325 
                 TPX2 
               
               
                 5 
                 ENSG00000089685 
                 BIRC5 
               
               
                 5 
                 ENSG00000090889 
                 KIF4A 
               
               
                 5 
                 ENSG00000091651 
                 ORC6 
               
               
                 5 
                 ENSG00000093009 
                 CDC45 
               
               
                 5 
                 ENSG00000094804 
                 CDC6 
               
               
                 5 
                 ENSG00000097046 
                 CDC7 
               
               
                 5 
                 ENSG00000100297 
                 MCM5 
               
               
                 5 
                 ENSG00000100526 
                 CDKN3 
               
               
                 5 
                 ENSG00000100600 
                 LGMN 
               
               
                 5 
                 ENSG00000101003 
                 GINS1 
               
               
                 5 
                 ENSG00000101057 
                 MYBL2 
               
               
                 5 
                 ENSG00000101412 
                 E2F1 
               
               
                 5 
                 ENSG00000101945 
                 SUV39H1 
               
               
                 5 
                 ENSG00000102384 
                 CENPI 
               
               
                 5 
                 ENSG00000104064 
                 GABPB1 
               
               
                 5 
                 ENSG00000104738 
                 MCM4 
               
               
                 5 
                 ENSG00000104889 
                 RNASEH2A 
               
               
                 5 
                 ENSG00000105011 
                 ASF1B 
               
               
                 5 
                 ENSG00000105135 
                 ILVBL 
               
               
                 5 
                 ENSG00000106462 
                 EZH2 
               
               
                 5 
                 ENSG00000108106 
                 UBE2S 
               
               
                 5 
                 ENSG00000109805 
                 NCAPG 
               
               
                 5 
                 ENSG00000111206 
                 FOXM1 
               
               
                 5 
                 ENSG00000111247 
                 RAD51AP1 
               
               
                 5 
                 ENSG00000111445 
                 RFC5 
               
               
                 5 
                 ENSG00000111602 
                 TIMELESS 
               
               
                 5 
                 ENSG00000112118 
                 MCM3 
               
               
                 5 
                 ENSG00000112578 
                 BYSL 
               
               
                 5 
                 ENSG00000112742 
                 TTK 
               
               
                 5 
                 ENSG00000112984 
                 KIF20A 
               
               
                 5 
                 ENSG00000113368 
                 LMNB1 
               
               
                 5 
                 ENSG00000113810 
                 SMC4 
               
               
                 5 
                 ENSG00000116212 
                 LRRC42 
               
               
                 5 
                 ENSG00000116478 
                 HDAC1 
               
               
                 5 
                 ENSG00000116830 
                 TTF2 
               
               
                 5 
                 ENSG00000117399 
                 CDC20 
               
               
                 5 
                 ENSG00000117632 
                 STMN1 
               
               
                 5 
                 ENSG00000117724 
                 CENPF 
               
               
                 5 
                 ENSG00000118193 
                 KIF14 
               
               
                 5 
                 ENSG00000119969 
                 HELLS 
               
               
                 5 
                 ENSG00000120254 
                 MTHFD1L 
               
               
                 5 
                 ENSG00000120539 
                 MASTL 
               
               
                 5 
                 ENSG00000120647 
                 CCDC77 
               
               
                 5 
                 ENSG00000120802 
                 TMPO 
               
               
                 5 
                 ENSG00000121152 
                 NCAPH 
               
               
                 5 
                 ENSG00000121621 
                 KIF18A 
               
               
                 5 
                 ENSG00000122483 
                 CCDC18 
               
               
                 5 
                 ENSG00000122566 
                 HNRNPA2B1 
               
               
                 5 
                 ENSG00000122952 
                 ZWINT 
               
               
                 5 
                 ENSG00000123219 
                 CENPK 
               
               
                 5 
                 ENSG00000123416 
                 TUBA1B 
               
               
                 5 
                 ENSG00000123485 
                 HJURP 
               
               
                 5 
                 ENSG00000123975 
                 CKS2 
               
               
                 5 
                 ENSG00000124207 
                 CSE1L 
               
               
                 5 
                 ENSG00000124766 
                 SOX4 
               
               
                 5 
                 ENSG00000125319 
                 C17orf53 
               
               
                 5 
                 ENSG00000125944 
                 HNRNPR 
               
               
                 5 
                 ENSG00000126787 
                 DLGAP5 
               
               
                 5 
                 ENSG00000127564 
                 PKMYT1 
               
               
                 5 
                 ENSG00000128274 
                 A4GALT 
               
               
                 5 
                 ENSG00000128944 
                 KNSTRN 
               
               
                 5 
                 ENSG00000129195 
                 FAM64A 
               
               
                 5 
                 ENSG00000130202 
                 PVRL2 
               
               
                 5 
                 ENSG00000131153 
                 GINS2 
               
               
                 5 
                 ENSG00000131269 
                 ABCB7 
               
               
                 5 
                 ENSG00000131747 
                 TOP2A 
               
               
                 5 
                 ENSG00000132313 
                 MRPL35 
               
               
                 5 
                 ENSG00000132646 
                 PCNA 
               
               
                 5 
                 ENSG00000134057 
                 CCNB1 
               
               
                 5 
                 ENSG00000134690 
                 CDCA8 
               
               
                 5 
                 ENSG00000135451 
                 TROAP 
               
               
                 5 
                 ENSG00000135476 
                 ESPL1 
               
               
                 5 
                 ENSG00000135763 
                 URB2 
               
               
                 5 
                 ENSG00000135823 
                 STX6 
               
               
                 5 
                 ENSG00000136108 
                 CKAP2 
               
               
                 5 
                 ENSG00000136122 
                 BORA 
               
               
                 5 
                 ENSG00000136492 
                 BRIP1 
               
               
                 5 
                 ENSG00000136943 
                 CTSV 
               
               
                 5 
                 ENSG00000137449 
                 CPEB2 
               
               
                 5 
                 ENSG00000137804 
                 NUSAP1 
               
               
                 5 
                 ENSG00000137807 
                 KIF23 
               
               
                 5 
                 ENSG00000137812 
                 CASC5 
               
               
                 5 
                 ENSG00000138092 
                 CENPO 
               
               
                 5 
                 ENSG00000138160 
                 KIF11 
               
               
                 5 
                 ENSG00000138180 
                 CEP55 
               
               
                 5 
                 ENSG00000138442 
                 WDR12 
               
               
                 5 
                 ENSG00000138778 
                 CENPE 
               
               
                 5 
                 ENSG00000139618 
                 BRCA2 
               
               
                 5 
                 ENSG00000139726 
                 DENR 
               
               
                 5 
                 ENSG00000139734 
                 DIAPH3 
               
               
                 5 
                 ENSG00000140525 
                 FANCI 
               
               
                 5 
                 ENSG00000142731 
                 PLK4 
               
               
                 5 
                 ENSG00000142945 
                 KIF2C 
               
               
                 5 
                 ENSG00000143228 
                 NUF2 
               
               
                 5 
                 ENSG00000143476 
                 DTL 
               
               
                 5 
                 ENSG00000143493 
                 INTS7 
               
               
                 5 
                 ENSG00000143621 
                 ILF2 
               
               
                 5 
                 ENSG00000143942 
                 CHAC2 
               
               
                 5 
                 ENSG00000144554 
                 FANCD2 
               
               
                 5 
                 ENSG00000145386 
                 CCNA2 
               
               
                 5 
                 ENSG00000145604 
                 SKP2 
               
               
                 5 
                 ENSG00000145907 
                 G3BP1 
               
               
                 5 
                 ENSG00000146410 
                 MTFR2 
               
               
                 5 
                 ENSG00000146670 
                 CDCA5 
               
               
                 5 
                 ENSG00000146918 
                 NCAPG2 
               
               
                 5 
                 ENSG00000147140 
                 NONO 
               
               
                 5 
                 ENSG00000147274 
                 RBMX 
               
               
                 5 
                 ENSG00000147536 
                 GINS4 
               
               
                 5 
                 ENSG00000148773 
                 MKI67 
               
               
                 5 
                 ENSG00000149554 
                 CHEK1 
               
               
                 5 
                 ENSG00000151287 
                 TEX30 
               
               
                 5 
                 ENSG00000153044 
                 CENPH 
               
               
                 5 
                 ENSG00000154839 
                 SKA1 
               
               
                 5 
                 ENSG00000154920 
                 EME1 
               
               
                 5 
                 ENSG00000156970 
                 BUB1B 
               
               
                 5 
                 ENSG00000157456 
                 CCNB2 
               
               
                 5 
                 ENSG00000159259 
                 CHAF1B 
               
               
                 5 
                 ENSG00000161800 
                 RACGAP1 
               
               
                 5 
                 ENSG00000161888 
                 SPC24 
               
               
                 5 
                 ENSG00000162062 
                 C16orf59 
               
               
                 5 
                 ENSG00000162063 
                 CCNF 
               
               
                 5 
                 ENSG00000163507 
                 KIAA1524 
               
               
                 5 
                 ENSG00000163808 
                 KIF15 
               
               
                 5 
                 ENSG00000163923 
                 RPL39L 
               
               
                 5 
                 ENSG00000163950 
                 SLBP 
               
               
                 5 
                 ENSG00000164045 
                 CDC25A 
               
               
                 5 
                 ENSG00000164109 
                 MAD2L1 
               
               
                 5 
                 ENSG00000164611 
                 PTTG1 
               
               
                 5 
                 ENSG00000165304 
                 MELK 
               
               
                 5 
                 ENSG00000165480 
                 SKA3 
               
               
                 5 
                 ENSG00000166451 
                 CENPN 
               
               
                 5 
                 ENSG00000166803 
                 KIAA0101 
               
               
                 5 
                 ENSG00000166851 
                 PLK1 
               
               
                 5 
                 ENSG00000167513 
                 CDT1 
               
               
                 5 
                 ENSG00000167900 
                 TK1 
               
               
                 5 
                 ENSG00000168078 
                 PBK 
               
               
                 5 
                 ENSG00000168393 
                 DTYMK 
               
               
                 5 
                 ENSG00000168411 
                 RFWD3 
               
               
                 5 
                 ENSG00000168496 
                 FEN1 
               
               
                 5 
                 ENSG00000168883 
                 USP39 
               
               
                 5 
                 ENSG00000169607 
                 CKAP2L 
               
               
                 5 
                 ENSG00000169679 
                 BUB1 
               
               
                 5 
                 ENSG00000170312 
                 CDK1 
               
               
                 5 
                 ENSG00000171241 
                 SHCBP1 
               
               
                 5 
                 ENSG00000171320 
                 ESCO2 
               
               
                 5 
                 ENSG00000171848 
                 RRM2 
               
               
                 5 
                 ENSG00000173207 
                 CKS1B 
               
               
                 5 
                 ENSG00000174442 
                 ZWILCH 
               
               
                 5 
                 ENSG00000175063 
                 UBE2C 
               
               
                 5 
                 ENSG00000175216 
                 CKAP5 
               
               
                 5 
                 ENSG00000175305 
                 CCNE2 
               
               
                 5 
                 ENSG00000176890 
                 TYMS 
               
               
                 5 
                 ENSG00000177191 
                 B3GNT8 
               
               
                 5 
                 ENSG00000178999 
                 AURKB 
               
               
                 5 
                 ENSG00000179051 
                 RCC2 
               
               
                 5 
                 ENSG00000179115 
                 FARSA 
               
               
                 5 
                 ENSG00000179632 
                 MAF1 
               
               
                 5 
                 ENSG00000182481 
                 KPNA2 
               
               
                 5 
                 ENSG00000182628 
                 SKA2 
               
               
                 5 
                 ENSG00000183763 
                 TRAIP 
               
               
                 5 
                 ENSG00000183814 
                 LIN9 
               
               
                 5 
                 ENSG00000183856 
                 IQGAP3 
               
               
                 5 
                 ENSG00000184661 
                 CDCA2 
               
               
                 5 
                 ENSG00000185480 
                 PARPBP 
               
               
                 5 
                 ENSG00000186185 
                 KIF18B 
               
               
                 5 
                 ENSG00000186871 
                 ERCC6L 
               
               
                 5 
                 ENSG00000187514 
                 PTMA 
               
               
                 5 
                 ENSG00000187741 
                 FANCA 
               
               
                 5 
                 ENSG00000188486 
                 H2AFX 
               
               
                 5 
                 ENSG00000188610 
                 FAM72B 
               
               
                 5 
                 ENSG00000189057 
                 FAM111B 
               
               
                 5 
                 ENSG00000196419 
                 XRCC6 
               
               
                 5 
                 ENSG00000196550 
                 FAM72A 
               
               
                 5 
                 ENSG00000196584 
                 XRCC2 
               
               
                 5 
                 ENSG00000198331 
                 HYLS1 
               
               
                 5 
                 ENSG00000198826 
                 ARHGAP11A 
               
               
                 5 
                 ENSG00000198901 
                 PRC1 
               
               
                 5 
                 ENSG00000203760 
                 CENPW 
               
               
                 5 
                 ENSG00000204392 
                 LSM2 
               
               
                 5 
                 ENSG00000213186 
                 TRIM59 
               
               
                 5 
                 ENSG00000215784 
                 FAM72D 
               
               
                 5 
                 ENSG00000228716 
                 DHFR 
               
               
                 5 
                 ENSG00000237649 
                 KIFC1 
               
               
                 5 
                 ENSG00000247077 
                 PGAM5 
               
               
                 6 
                 ENSG00000001460 
                 STPG1 
               
               
                 6 
                 ENSG00000003096 
                 KLHL13 
               
               
                 6 
                 ENSG00000003989 
                 SLC7A2 
               
               
                 6 
                 ENSG00000004838 
                 ZMYND10 
               
               
                 6 
                 ENSG00000004848 
                 ARX 
               
               
                 6 
                 ENSG00000005100 
                 DHX33 
               
               
                 6 
                 ENSG00000005448 
                 WDR54 
               
               
                 6 
                 ENSG00000006740 
                 ARHGAP44 
               
               
                 6 
                 ENSG00000006837 
                 CDKL3 
               
               
                 6 
                 ENSG00000007062 
                 PROM1 
               
               
                 6 
                 ENSG00000007174 
                 DNAH9 
               
               
                 6 
                 ENSG00000007237 
                 GAS7 
               
               
                 6 
                 ENSG00000007384 
                 RHBDF1 
               
               
                 6 
                 ENSG00000007866 
                 TEAD3 
               
               
                 6 
                 ENSG00000008083 
                 JARID2 
               
               
                 6 
                 ENSG00000010361 
                 FUZ 
               
               
                 6 
                 ENSG00000010626 
                 LRRC23 
               
               
                 6 
                 ENSG00000011143 
                 MKS1 
               
               
                 6 
                 ENSG00000011295 
                 TTC19 
               
               
                 6 
                 ENSG00000011485 
                 PPP5C 
               
               
                 6 
                 ENSG00000016402 
                 IL20RA 
               
               
                 6 
                 ENSG00000016864 
                 GLT8D1 
               
               
                 6 
                 ENSG00000021300 
                 PLEKHB1 
               
               
                 6 
                 ENSG00000021645 
                 NRXN3 
               
               
                 6 
                 ENSG00000024862 
                 CCDC28A 
               
               
                 6 
                 ENSG00000025156 
                 HSF2 
               
               
                 6 
                 ENSG00000025772 
                 TOMM34 
               
               
                 6 
                 ENSG00000026508 
                 CD44 
               
               
                 6 
                 ENSG00000032742 
                 IFT88 
               
               
                 6 
                 ENSG00000034239 
                 EFCAB1 
               
               
                 6 
                 ENSG00000036672 
                 USP2 
               
               
                 6 
                 ENSG00000037474 
                 NSUN2 
               
               
                 6 
                 ENSG00000039139 
                 DNAH5 
               
               
                 6 
                 ENSG00000042317 
                 SPATA7 
               
               
                 6 
                 ENSG00000043514 
                 TRIT1 
               
               
                 6 
                 ENSG00000048342 
                 CC2D2A 
               
               
                 6 
                 ENSG00000048471 
                 SNX29 
               
               
                 6 
                 ENSG00000048991 
                 R3HDM1 
               
               
                 6 
                 ENSG00000049319 
                 SRD5A2 
               
               
                 6 
                 ENSG00000049759 
                 NEDD4L 
               
               
                 6 
                 ENSG00000049769 
                 PPP1R3F 
               
               
                 6 
                 ENSG00000050327 
                 ARHGEF5 
               
               
                 6 
                 ENSG00000051341 
                 POLQ 
               
               
                 6 
                 ENSG00000054219 
                 LY75 
               
               
                 6 
                 ENSG00000054282 
                 SDCCAG8 
               
               
                 6 
                 ENSG00000054392 
                 HHAT 
               
               
                 6 
                 ENSG00000054983 
                 GALC 
               
               
                 6 
                 ENSG00000056998 
                 GYG2 
               
               
                 6 
                 ENSG00000057019 
                 DCBLD2 
               
               
                 6 
                 ENSG00000058085 
                 LAMC2 
               
               
                 6 
                 ENSG00000064199 
                 SPA17 
               
               
                 6 
                 ENSG00000064692 
                 SNCAIP 
               
               
                 6 
                 ENSG00000064999 
                 ANKS1A 
               
               
                 6 
                 ENSG00000065357 
                 DGKA 
               
               
                 6 
                 ENSG00000065491 
                 TBC1D22B 
               
               
                 6 
                 ENSG00000065970 
                 FOXJ2 
               
               
                 6 
                 ENSG00000066084 
                 DIP2B 
               
               
                 6 
                 ENSG00000066185 
                 ZMYND12 
               
               
                 6 
                 ENSG00000066248 
                 NGEF 
               
               
                 6 
                 ENSG00000066629 
                 EML1 
               
               
                 6 
                 ENSG00000067208 
                 EVI5 
               
               
                 6 
                 ENSG00000067369 
                 TP53BP1 
               
               
                 6 
                 ENSG00000068650 
                 ATP11A 
               
               
                 6 
                 ENSG00000068885 
                 IFT80 
               
               
                 6 
                 ENSG00000068971 
                 PPP2R5B 
               
               
                 6 
                 ENSG00000070444 
                 MNT 
               
               
                 6 
                 ENSG00000070718 
                 AP3M2 
               
               
                 6 
                 ENSG00000070731 
                 ST6GALNAC2 
               
               
                 6 
                 ENSG00000070761 
                 C16orf80 
               
               
                 6 
                 ENSG00000071539 
                 TRIP13 
               
               
                 6 
                 ENSG00000072133 
                 RPS6KA6 
               
               
                 6 
                 ENSG00000072422 
                 RHOBTB1 
               
               
                 6 
                 ENSG00000073050 
                 XRCC1 
               
               
                 6 
                 ENSG00000073464 
                 CLCN4 
               
               
                 6 
                 ENSG00000074621 
                 SLC24A1 
               
               
                 6 
                 ENSG00000074964 
                 ARHGEF10L 
               
               
                 6 
                 ENSG00000075142 
                 SRI 
               
               
                 6 
                 ENSG00000075240 
                 GRAMD4 
               
               
                 6 
                 ENSG00000075568 
                 TMEM131 
               
               
                 6 
                 ENSG00000075945 
                 KIFAP3 
               
               
                 6 
                 ENSG00000077327 
                 SPAG6 
               
               
                 6 
                 ENSG00000077514 
                 POLD3 
               
               
                 6 
                 ENSG00000077800 
                 FKBP6 
               
               
                 6 
                 ENSG00000078246 
                 TULP3 
               
               
                 6 
                 ENSG00000078487 
                 ZCWPW1 
               
               
                 6 
                 ENSG00000078900 
                 TP73 
               
               
                 6 
                 ENSG00000079156 
                 OSBPL6 
               
               
                 6 
                 ENSG00000079335 
                 CDC14A 
               
               
                 6 
                 ENSG00000080298 
                 RFX3 
               
               
                 6 
                 ENSG00000080572 
                 PIH1D3 
               
               
                 6 
                 ENSG00000080824 
                 HSP90AA1 
               
               
                 6 
                 ENSG00000081870 
                 HSPB11 
               
               
                 6 
                 ENSG00000083290 
                 ULK2 
               
               
                 6 
                 ENSG00000084764 
                 MAPRE3 
               
               
                 6 
                 ENSG00000085063 
                 CD59 
               
               
                 6 
                 ENSG00000085433 
                 WDR47 
               
               
                 6 
                 ENSG00000086102 
                 NFX1 
               
               
                 6 
                 ENSG00000086200 
                 IPO11 
               
               
                 6 
                 ENSG00000087053 
                 MTMR2 
               
               
                 6 
                 ENSG00000087152 
                 ATXN7L3 
               
               
                 6 
                 ENSG00000087365 
                 SF3B2 
               
               
                 6 
                 ENSG00000087510 
                 TFAP2C 
               
               
                 6 
                 ENSG00000087903 
                 RFX2 
               
               
                 6 
                 ENSG00000088053 
                 GP6 
               
               
                 6 
                 ENSG00000088320 
                 REM1 
               
               
                 6 
                 ENSG00000088727 
                 KIF9 
               
               
                 6 
                 ENSG00000088833 
                 NSFL1C 
               
               
                 6 
                 ENSG00000088970 
                 PLK1S1 
               
               
                 6 
                 ENSG00000088986 
                 DYNLL1 
               
               
                 6 
                 ENSG00000089060 
                 SLC8B1 
               
               
                 6 
                 ENSG00000089091 
                 DZANK1 
               
               
                 6 
                 ENSG00000089101 
                 C20orf26 
               
               
                 6 
                 ENSG00000089123 
                 TASP1 
               
               
                 6 
                 ENSG00000090273 
                 NUDC 
               
               
                 6 
                 ENSG00000090661 
                 CERS4 
               
               
                 6 
                 ENSG00000090971 
                 NAT14 
               
               
                 6 
                 ENSG00000091181 
                 IL5RA 
               
               
                 6 
                 ENSG00000092850 
                 TEKT2 
               
               
                 6 
                 ENSG00000095261 
                 PSMD5 
               
               
                 6 
                 ENSG00000095319 
                 NUP188 
               
               
                 6 
                 ENSG00000096433 
                 ITPR3 
               
               
                 6 
                 ENSG00000096872 
                 IFT74 
               
               
                 6 
                 ENSG00000100012 
                 SEC14L3 
               
               
                 6 
                 ENSG00000100124 
                 ANKRD54 
               
               
                 6 
                 ENSG00000100162 
                 CENPM 
               
               
                 6 
                 ENSG00000100211 
                 CBY1 
               
               
                 6 
                 ENSG00000100218 
                 RTDR1 
               
               
                 6 
                 ENSG00000100228 
                 RAB36 
               
               
                 6 
                 ENSG00000100271 
                 TTLL1 
               
               
                 6 
                 ENSG00000100294 
                 MCAT 
               
               
                 6 
                 ENSG00000100345 
                 MYH9 
               
               
                 6 
                 ENSG00000100418 
                 DESI1 
               
               
                 6 
                 ENSG00000100422 
                 CERK 
               
               
                 6 
                 ENSG00000100441 
                 KHNYN 
               
               
                 6 
                 ENSG00000100462 
                 PRMT5 
               
               
                 6 
                 ENSG00000100490 
                 CDKL1 
               
               
                 6 
                 ENSG00000100583 
                 SAMD15 
               
               
                 6 
                 ENSG00000100591 
                 AHSA1 
               
               
                 6 
                 ENSG00000100625 
                 SIX4 
               
               
                 6 
                 ENSG00000100784 
                 RPS6KA5 
               
               
                 6 
                 ENSG00000101052 
                 IFT52 
               
               
                 6 
                 ENSG00000101222 
                 SPEF1 
               
               
                 6 
                 ENSG00000101448 
                 EPPIN 
               
               
                 6 
                 ENSG00000101928 
                 MOSPD1 
               
               
                 6 
                 ENSG00000102048 
                 ASB9 
               
               
                 6 
                 ENSG00000102230 
                 PCYT1B 
               
               
                 6 
                 ENSG00000102349 
                 KLF8 
               
               
                 6 
                 ENSG00000102466 
                 FGF14 
               
               
                 6 
                 ENSG00000102543 
                 CDADC1 
               
               
                 6 
                 ENSG00000102738 
                 MRPS31 
               
               
                 6 
                 ENSG00000102743 
                 SLC25A15 
               
               
                 6 
                 ENSG00000102781 
                 KATNAL1 
               
               
                 6 
                 ENSG00000102886 
                 GDPD3 
               
               
                 6 
                 ENSG00000102996 
                 MMP15 
               
               
                 6 
                 ENSG00000103021 
                 CCDC113 
               
               
                 6 
                 ENSG00000103042 
                 SLC38A7 
               
               
                 6 
                 ENSG00000103160 
                 HSDL1 
               
               
                 6 
                 ENSG00000103174 
                 NAGPA 
               
               
                 6 
                 ENSG00000103194 
                 USP10 
               
               
                 6 
                 ENSG00000103260 
                 METRN 
               
               
                 6 
                 ENSG00000103351 
                 CLUAP1 
               
               
                 6 
                 ENSG00000103494 
                 RPGRIP1L 
               
               
                 6 
                 ENSG00000103540 
                 CCP110 
               
               
                 6 
                 ENSG00000103599 
                 IQCH 
               
               
                 6 
                 ENSG00000103647 
                 CORO2B 
               
               
                 6 
                 ENSG00000103740 
                 ACSBG1 
               
               
                 6 
                 ENSG00000103994 
                 ZNF106 
               
               
                 6 
                 ENSG00000103995 
                 CEP152 
               
               
                 6 
                 ENSG00000104237 
                 RP1 
               
               
                 6 
                 ENSG00000104361 
                 NIPAL2 
               
               
                 6 
                 ENSG00000104427 
                 ZC2HC1A 
               
               
                 6 
                 ENSG00000104472 
                 CHRAC1 
               
               
                 6 
                 ENSG00000104490 
                 NCALD 
               
               
                 6 
                 ENSG00000104549 
                 SQLE 
               
               
                 6 
                 ENSG00000104723 
                 TUSC3 
               
               
                 6 
                 ENSG00000105258 
                 POLR2I 
               
               
                 6 
                 ENSG00000105278 
                 ZFR2 
               
               
                 6 
                 ENSG00000105519 
                 CAPS 
               
               
                 6 
                 ENSG00000105948 
                 TTC26 
               
               
                 6 
                 ENSG00000105982 
                 RNF32 
               
               
                 6 
                 ENSG00000106012 
                 IQCE 
               
               
                 6 
                 ENSG00000106049 
                 HIBADH 
               
               
                 6 
                 ENSG00000106052 
                 TAX1BP1 
               
               
                 6 
                 ENSG00000106125 
                 FAM188B 
               
               
                 6 
                 ENSG00000106399 
                 RPA3 
               
               
                 6 
                 ENSG00000106459 
                 NRF1 
               
               
                 6 
                 ENSG00000106477 
                 CEP41 
               
               
                 6 
                 ENSG00000106701 
                 FSD1L 
               
               
                 6 
                 ENSG00000106992 
                 AK1 
               
               
                 6 
                 ENSG00000107185 
                 RGP1 
               
               
                 6 
                 ENSG00000107186 
                 MPDZ 
               
               
                 6 
                 ENSG00000107249 
                 GLIS3 
               
               
                 6 
                 ENSG00000107521 
                 HPS1 
               
               
                 6 
                 ENSG00000107816 
                 LZTS2 
               
               
                 6 
                 ENSG00000107957 
                 SH3PXD2A 
               
               
                 6 
                 ENSG00000108187 
                 PBLD 
               
               
                 6 
                 ENSG00000108395 
                 TRIM37 
               
               
                 6 
                 ENSG00000108406 
                 DHX40 
               
               
                 6 
                 ENSG00000108479 
                 GALK1 
               
               
                 6 
                 ENSG00000108641 
                 B9D1 
               
               
                 6 
                 ENSG00000108733 
                 PEX12 
               
               
                 6 
                 ENSG00000108753 
                 HNF1B 
               
               
                 6 
                 ENSG00000108819 
                 PPP1R9B 
               
               
                 6 
                 ENSG00000108946 
                 PRKAR1A 
               
               
                 6 
                 ENSG00000108947 
                 EFNB3 
               
               
                 6 
                 ENSG00000109083 
                 IFT20 
               
               
                 6 
                 ENSG00000109171 
                 SLAIN2 
               
               
                 6 
                 ENSG00000109501 
                 WFS1 
               
               
                 6 
                 ENSG00000109680 
                 TBC1D19 
               
               
                 6 
                 ENSG00000109685 
                 WHSC1 
               
               
                 6 
                 ENSG00000109762 
                 SNX25 
               
               
                 6 
                 ENSG00000109771 
                 LRP2BP 
               
               
                 6 
                 ENSG00000109944 
                 C11orf63 
               
               
                 6 
                 ENSG00000110025 
                 SNX15 
               
               
                 6 
                 ENSG00000110318 
                 KIAA1377 
               
               
                 6 
                 ENSG00000110841 
                 PPFIBP1 
               
               
                 6 
                 ENSG00000111145 
                 ELK3 
               
               
                 6 
                 ENSG00000111218 
                 PRMT8 
               
               
                 6 
                 ENSG00000111254 
                 AKAP3 
               
               
                 6 
                 ENSG00000111262 
                 KCNA1 
               
               
                 6 
                 ENSG00000111321 
                 LTBR 
               
               
                 6 
                 ENSG00000111325 
                 OGFOD2 
               
               
                 6 
                 ENSG00000111450 
                 STX2 
               
               
                 6 
                 ENSG00000111554 
                 MDM1 
               
               
                 6 
                 ENSG00000111647 
                 UHRF1BP1L 
               
               
                 6 
                 ENSG00000111674 
                 ENO2 
               
               
                 6 
                 ENSG00000111728 
                 ST8SIA1 
               
               
                 6 
                 ENSG00000111834 
                 RSPH4A 
               
               
                 6 
                 ENSG00000111837 
                 MAK 
               
               
                 6 
                 ENSG00000111877 
                 MCM9 
               
               
                 6 
                 ENSG00000111879 
                 FAM184A 
               
               
                 6 
                 ENSG00000111907 
                 TPD52L1 
               
               
                 6 
                 ENSG00000111961 
                 SASH1 
               
               
                 6 
                 ENSG00000112183 
                 RBM24 
               
               
                 6 
                 ENSG00000112186 
                 CAP2 
               
               
                 6 
                 ENSG00000112530 
                 PACRG 
               
               
                 6 
                 ENSG00000112539 
                 C6orf118 
               
               
                 6 
                 ENSG00000112559 
                 MDFI 
               
               
                 6 
                 ENSG00000112584 
                 FAM120B 
               
               
                 6 
                 ENSG00000112667 
                 DNPH1 
               
               
                 6 
                 ENSG00000112796 
                 ENPP5 
               
               
                 6 
                 ENSG00000112981 
                 NME5 
               
               
                 6 
                 ENSG00000113141 
                 IK 
               
               
                 6 
                 ENSG00000113318 
                 MSH3 
               
               
                 6 
                 ENSG00000113456 
                 RAD1 
               
               
                 6 
                 ENSG00000113583 
                 C5orf15 
               
               
                 6 
                 ENSG00000113645 
                 WWC1 
               
               
                 6 
                 ENSG00000113946 
                 CLDN16 
               
               
                 6 
                 ENSG00000113966 
                 ARL6 
               
               
                 6 
                 ENSG00000114446 
                 IFT57 
               
               
                 6 
                 ENSG00000114455 
                 HHLA2 
               
               
                 6 
                 ENSG00000114473 
                 IQCG 
               
               
                 6 
                 ENSG00000114656 
                 KIAA1257 
               
               
                 6 
                 ENSG00000114670 
                 NEK11 
               
               
                 6 
                 ENSG00000114805 
                 PLCH1 
               
               
                 6 
                 ENSG00000114904 
                 NEK4 
               
               
                 6 
                 ENSG00000115107 
                 STEAP3 
               
               
                 6 
                 ENSG00000115145 
                 STAM2 
               
               
                 6 
                 ENSG00000115216 
                 NRBP1 
               
               
                 6 
                 ENSG00000115423 
                 DNAH6 
               
               
                 6 
                 ENSG00000115425 
                 PECR 
               
               
                 6 
                 ENSG00000115486 
                 GGCX 
               
               
                 6 
                 ENSG00000115685 
                 PPP1R7 
               
               
                 6 
                 ENSG00000115750 
                 TAF1B 
               
               
                 6 
                 ENSG00000115947 
                 ORC4 
               
               
                 6 
                 ENSG00000115970 
                 THADA 
               
               
                 6 
                 ENSG00000115998 
                 C2orf42 
               
               
                 6 
                 ENSG00000116032 
                 GRIN3B 
               
               
                 6 
                 ENSG00000116127 
                 ALMS1 
               
               
                 6 
                 ENSG00000116128 
                 BCL9 
               
               
                 6 
                 ENSG00000116525 
                 TRIM62 
               
               
                 6 
                 ENSG00000116675 
                 DNAJC6 
               
               
                 6 
                 ENSG00000116793 
                 PHTF1 
               
               
                 6 
                 ENSG00000116885 
                 OSCP1 
               
               
                 6 
                 ENSG00000116957 
                 TBCE 
               
               
                 6 
                 ENSG00000117016 
                 RIMS3 
               
               
                 6 
                 ENSG00000117477 
                 CCDC181 
               
               
                 6 
                 ENSG00000117602 
                 RCAN3 
               
               
                 6 
                 ENSG00000118096 
                 IFT46 
               
               
                 6 
                 ENSG00000118307 
                 CASC1 
               
               
                 6 
                 ENSG00000118407 
                 FILIP1 
               
               
                 6 
                 ENSG00000118418 
                 HMGN3 
               
               
                 6 
                 ENSG00000118420 
                 UBE3D 
               
               
                 6 
                 ENSG00000118690 
                 ARMC2 
               
               
                 6 
                 ENSG00000118965 
                 WDR35 
               
               
                 6 
                 ENSG00000118997 
                 DNAH7 
               
               
                 6 
                 ENSG00000119147 
                 C2orf40 
               
               
                 6 
                 ENSG00000119328 
                 FAM206A 
               
               
                 6 
                 ENSG00000119333 
                 WDR34 
               
               
                 6 
                 ENSG00000119397 
                 CNTRL 
               
               
                 6 
                 ENSG00000119401 
                 TRIM32 
               
               
                 6 
                 ENSG00000119402 
                 FBXW2 
               
               
                 6 
                 ENSG00000119636 
                 CCDC176 
               
               
                 6 
                 ENSG00000119640 
                 ACYP1 
               
               
                 6 
                 ENSG00000119650 
                 IFT43 
               
               
                 6 
                 ENSG00000119661 
                 DNAL1 
               
               
                 6 
                 ENSG00000119685 
                 TTLL5 
               
               
                 6 
                 ENSG00000119689 
                 DLST 
               
               
                 6 
                 ENSG00000119698 
                 PPP4R4 
               
               
                 6 
                 ENSG00000119703 
                 ZC2HC1C 
               
               
                 6 
                 ENSG00000119782 
                 FKBP1B 
               
               
                 6 
                 ENSG00000120051 
                 CCDC147 
               
               
                 6 
                 ENSG00000120055 
                 C10orf95 
               
               
                 6 
                 ENSG00000120256 
                 LRP11 
               
               
                 6 
                 ENSG00000120262 
                 CCDC170 
               
               
                 6 
                 ENSG00000120279 
                 MYCT1 
               
               
                 6 
                 ENSG00000120306 
                 CYSTM1 
               
               
                 6 
                 ENSG00000120658 
                 ENOX1 
               
               
                 6 
                 ENSG00000120685 
                 PROSER1 
               
               
                 6 
                 ENSG00000120694 
                 HSPH1 
               
               
                 6 
                 ENSG00000121057 
                 AKAP1 
               
               
                 6 
                 ENSG00000121413 
                 ZSCAN18 
               
               
                 6 
                 ENSG00000121486 
                 TRMT1L 
               
               
                 6 
                 ENSG00000121671 
                 CRY2 
               
               
                 6 
                 ENSG00000122376 
                 FAM35A 
               
               
                 6 
                 ENSG00000122507 
                 BBS9 
               
               
                 6 
                 ENSG00000122970 
                 IFT81 
               
               
                 6 
                 ENSG00000123607 
                 TTC21B 
               
               
                 6 
                 ENSG00000123810 
                 B9D2 
               
               
                 6 
                 ENSG00000123977 
                 DAW1 
               
               
                 6 
                 ENSG00000124074 
                 ENKD1 
               
               
                 6 
                 ENSG00000124237 
                 C20orf85 
               
               
                 6 
                 ENSG00000124678 
                 TCP11 
               
               
                 6 
                 ENSG00000124749 
                 COL21A1 
               
               
                 6 
                 ENSG00000125124 
                 BBS2 
               
               
                 6 
                 ENSG00000125384 
                 PTGER2 
               
               
                 6 
                 ENSG00000125409 
                 TEKT3 
               
               
                 6 
                 ENSG00000125482 
                 TTF1 
               
               
                 6 
                 ENSG00000125531 
                 C20orf195 
               
               
                 6 
                 ENSG00000125733 
                 TRIP10 
               
               
                 6 
                 ENSG00000125779 
                 PANK2 
               
               
                 6 
                 ENSG00000125871 
                 MGME1 
               
               
                 6 
                 ENSG00000125968 
                 ID1 
               
               
                 6 
                 ENSG00000125991 
                 ERGIC3 
               
               
                 6 
                 ENSG00000126107 
                 HECTD3 
               
               
                 6 
                 ENSG00000126391 
                 FRMD8 
               
               
                 6 
                 ENSG00000126432 
                 PRDX5 
               
               
                 6 
                 ENSG00000126773 
                 PCNXL4 
               
               
                 6 
                 ENSG00000126777 
                 KTN1 
               
               
                 6 
                 ENSG00000126778 
                 SIX1 
               
               
                 6 
                 ENSG00000126870 
                 WDR60 
               
               
                 6 
                 ENSG00000127399 
                 LRRC61 
               
               
                 6 
                 ENSG00000127824 
                 TUBA4A 
               
               
                 6 
                 ENSG00000127863 
                 TNFRSF19 
               
               
                 6 
                 ENSG00000127914 
                 AKAP9 
               
               
                 6 
                 ENSG00000127952 
                 STYXL1 
               
               
                 6 
                 ENSG00000128346 
                 C22orf23 
               
               
                 6 
                 ENSG00000128408 
                 RIBC2 
               
               
                 6 
                 ENSG00000128536 
                 CDHR3 
               
               
                 6 
                 ENSG00000128581 
                 RABL5 
               
               
                 6 
                 ENSG00000128607 
                 KLHDC10 
               
               
                 6 
                 ENSG00000128881 
                 TTBK2 
               
               
                 6 
                 ENSG00000128891 
                 C15orf57 
               
               
                 6 
                 ENSG00000129007 
                 CALML4 
               
               
                 6 
                 ENSG00000129028 
                 THAP10 
               
               
                 6 
                 ENSG00000129151 
                 BBOX1 
               
               
                 6 
                 ENSG00000129295 
                 LRRC6 
               
               
                 6 
                 ENSG00000129521 
                 EGLN3 
               
               
                 6 
                 ENSG00000129654 
                 FOXJ1 
               
               
                 6 
                 ENSG00000129951 
               
               
                 6 
                 ENSG00000130177 
                 CDC16 
               
               
                 6 
                 ENSG00000130363 
                 RSPH3 
               
               
                 6 
                 ENSG00000130413 
                 STK33 
               
               
                 6 
                 ENSG00000130433 
                 CACNG6 
               
               
                 6 
                 ENSG00000130511 
                 SSBP4 
               
               
                 6 
                 ENSG00000130560 
                 UBAC1 
               
               
                 6 
                 ENSG00000130640 
                 TUBGCP2 
               
               
                 6 
                 ENSG00000130762 
                 ARHGEF16 
               
               
                 6 
                 ENSG00000130770 
                 ATPIF1 
               
               
                 6 
                 ENSG00000130962 
                 PRRG1 
               
               
                 6 
                 ENSG00000131437 
                 KIF3A 
               
               
                 6 
                 ENSG00000131470 
                 PSMC3IP 
               
               
                 6 
                 ENSG00000131697 
                 NPHP4 
               
               
                 6 
                 ENSG00000131711 
                 MAP1B 
               
               
                 6 
                 ENSG00000131828 
                 PDHA1 
               
               
                 6 
                 ENSG00000131848 
                 ZSCAN5A 
               
               
                 6 
                 ENSG00000131941 
                 RHPN2 
               
               
                 6 
                 ENSG00000131969 
                 ABHD12B 
               
               
                 6 
                 ENSG00000132003 
                 ZSWIM4 
               
               
                 6 
                 ENSG00000132004 
                 FBXW9 
               
               
                 6 
                 ENSG00000132010 
                 ZNF20 
               
               
                 6 
                 ENSG00000132122 
                 SPATA6 
               
               
                 6 
                 ENSG00000132139 
                 GAS2L2 
               
               
                 6 
                 ENSG00000132259 
                 CNGA4 
               
               
                 6 
                 ENSG00000132321 
                 IQCA1 
               
               
                 6 
                 ENSG00000132549 
                 VPS13B 
               
               
                 6 
                 ENSG00000132554 
                 RGS22 
               
               
                 6 
                 ENSG00000132640 
                 BTBD3 
               
               
                 6 
                 ENSG00000132664 
                 POLR3F 
               
               
                 6 
                 ENSG00000132768 
                 DPH2 
               
               
                 6 
                 ENSG00000133056 
                 PIK3C2B 
               
               
                 6 
                 ENSG00000133065 
                 SLC41A1 
               
               
                 6 
                 ENSG00000133104 
                 SPG20 
               
               
                 6 
                 ENSG00000133115 
                 STOML3 
               
               
                 6 
                 ENSG00000133131 
                 MORC4 
               
               
                 6 
                 ENSG00000133216 
                 EPHB2 
               
               
                 6 
                 ENSG00000133256 
                 PDE6B 
               
               
                 6 
                 ENSG00000133488 
                 SEC14L4 
               
               
                 6 
                 ENSG00000133627 
                 ACTR3B 
               
               
                 6 
                 ENSG00000133640 
                 LRRIQ1 
               
               
                 6 
                 ENSG00000133678 
                 TMEM254 
               
               
                 6 
                 ENSG00000133739 
                 LRRCC1 
               
               
                 6 
                 ENSG00000133958 
                 UNC79 
               
               
                 6 
                 ENSG00000134138 
                 MEIS2 
               
               
                 6 
                 ENSG00000134247 
                 PTGFRN 
               
               
                 6 
                 ENSG00000135070 
                 ISCA1 
               
               
                 6 
                 ENSG00000135205 
                 CCDC146 
               
               
                 6 
                 ENSG00000135245 
                 HILPDA 
               
               
                 6 
                 ENSG00000135315 
                 KIAA1009 
               
               
                 6 
                 ENSG00000135338 
                 LCA5 
               
               
                 6 
                 ENSG00000135406 
                 PRPH 
               
               
                 6 
                 ENSG00000135519 
                 KCNH3 
               
               
                 6 
                 ENSG00000135535 
                 CD164 
               
               
                 6 
                 ENSG00000135537 
                 LACE1 
               
               
                 6 
                 ENSG00000135549 
                 PKIB 
               
               
                 6 
                 ENSG00000135597 
                 REPS1 
               
               
                 6 
                 ENSG00000135931 
                 ARMC9 
               
               
                 6 
                 ENSG00000135951 
                 TSGA10 
               
               
                 6 
                 ENSG00000135966 
                 TGFBRAP1 
               
               
                 6 
                 ENSG00000136044 
                 APPL2 
               
               
                 6 
                 ENSG00000136319 
                 TTC5 
               
               
                 6 
                 ENSG00000136448 
                 NMT1 
               
               
                 6 
                 ENSG00000136449 
                 MYCBPAP 
               
               
                 6 
                 ENSG00000136451 
                 VEZF1 
               
               
                 6 
                 ENSG00000136715 
                 SAP130 
               
               
                 6 
                 ENSG00000136811 
                 ODF2 
               
               
                 6 
                 ENSG00000136918 
                 WDR38 
               
               
                 6 
                 ENSG00000137266 
                 SLC22A23 
               
               
                 6 
                 ENSG00000137274 
                 BPHL 
               
               
                 6 
                 ENSG00000137414 
                 FAM8A1 
               
               
                 6 
                 ENSG00000137434 
                 C6orf52 
               
               
                 6 
                 ENSG00000137473 
                 TTC29 
               
               
                 6 
                 ENSG00000137494 
                 ANKRD42 
               
               
                 6 
                 ENSG00000137601 
                 NEK1 
               
               
                 6 
                 ENSG00000137691 
                 C11orf70 
               
               
                 6 
                 ENSG00000137707 
                 BTG4 
               
               
                 6 
                 ENSG00000137819 
                 PAQR5 
               
               
                 6 
                 ENSG00000137821 
                 LRRC49 
               
               
                 6 
                 ENSG00000137960 
                 GIPC2 
               
               
                 6 
                 ENSG00000138002 
                 IFT172 
               
               
                 6 
                 ENSG00000138036 
                 DYNC2LI1 
               
               
                 6 
                 ENSG00000138041 
                 SMEK2 
               
               
                 6 
                 ENSG00000138175 
                 ARL3 
               
               
                 6 
                 ENSG00000138400 
                 MDH1B 
               
               
                 6 
                 ENSG00000138433 
                 CIR1 
               
               
                 6 
                 ENSG00000138443 
                 ABI2 
               
               
                 6 
                 ENSG00000138587 
                 MNS1 
               
               
                 6 
                 ENSG00000138622 
                 HCN4 
               
               
                 6 
                 ENSG00000138640 
                 FAM13A 
               
               
                 6 
                 ENSG00000138670 
                 RASGEF1B 
               
               
                 6 
                 ENSG00000138769 
                 CDKL2 
               
               
                 6 
                 ENSG00000138771 
                 SHROOM3 
               
               
                 6 
                 ENSG00000138823 
                 MTTP 
               
               
                 6 
                 ENSG00000139537 
                 CCDC65 
               
               
                 6 
                 ENSG00000139624 
                 CERS5 
               
               
                 6 
                 ENSG00000139714 
                 MORN3 
               
               
                 6 
                 ENSG00000139971 
                 C14orf37 
               
               
                 6 
                 ENSG00000139974 
                 SLC38A6 
               
               
                 6 
                 ENSG00000140025 
                 EFCAB11 
               
               
                 6 
                 ENSG00000140043 
                 PTGR2 
               
               
                 6 
                 ENSG00000140057 
                 AK7 
               
               
                 6 
                 ENSG00000140284 
                 SLC27A2 
               
               
                 6 
                 ENSG00000140403 
                 DNAJA4 
               
               
                 6 
                 ENSG00000140463 
                 BBS4 
               
               
                 6 
                 ENSG00000140481 
                 CCDC33 
               
               
                 6 
                 ENSG00000140527 
                 WDR93 
               
               
                 6 
                 ENSG00000140564 
                 FURIN 
               
               
                 6 
                 ENSG00000140600 
                 SH3GL3 
               
               
                 6 
                 ENSG00000140632 
                 GLYR1 
               
               
                 6 
                 ENSG00000140876 
                 NUDT7 
               
               
                 6 
                 ENSG00000141012 
                 GALNS 
               
               
                 6 
                 ENSG00000141013 
                 GAS8 
               
               
                 6 
                 ENSG00000141098 
                 GFOD2 
               
               
                 6 
                 ENSG00000141294 
                 LRRC46 
               
               
                 6 
                 ENSG00000141376 
                 BCAS3 
               
               
                 6 
                 ENSG00000141499 
                 WRAP53 
               
               
                 6 
                 ENSG00000141510 
                 TP53 
               
               
                 6 
                 ENSG00000141580 
                 WDR45B 
               
               
                 6 
                 ENSG00000141665 
                 FBXO15 
               
               
                 6 
                 ENSG00000142621 
                 FHAD1 
               
               
                 6 
                 ENSG00000142655 
                 PEX14 
               
               
                 6 
                 ENSG00000142677 
                 IL22RA1 
               
               
                 6 
                 ENSG00000143093 
                 STRIP1 
               
               
                 6 
                 ENSG00000143156 
                 NME7 
               
               
                 6 
                 ENSG00000143179 
                 UCK2 
               
               
                 6 
                 ENSG00000143222 
                 UFC1 
               
               
                 6 
                 ENSG00000143258 
                 USP21 
               
               
                 6 
                 ENSG00000143479 
                 DYRK3 
               
               
                 6 
                 ENSG00000143499 
                 SMYD2 
               
               
                 6 
                 ENSG00000143537 
                 ADAM15 
               
               
                 6 
                 ENSG00000143595 
                 AQP10 
               
               
                 6 
                 ENSG00000143633 
                 C1orf131 
               
               
                 6 
                 ENSG00000143653 
                 SCCPDH 
               
               
                 6 
                 ENSG00000143786 
                 CNIH3 
               
               
                 6 
                 ENSG00000143933 
                 CALM2 
               
               
                 6 
                 ENSG00000143951 
                 WDPCP 
               
               
                 6 
                 ENSG00000144061 
                 NPHP1 
               
               
                 6 
                 ENSG00000144233 
                 AMMECR1L 
               
               
                 6 
                 ENSG00000144451 
                 SPAG16 
               
               
                 6 
                 ENSG00000144504 
                 ANKMY1 
               
               
                 6 
                 ENSG00000145075 
                 CCDC39 
               
               
                 6 
                 ENSG00000145331 
                 TRMT10A 
               
               
                 6 
                 ENSG00000145414 
                 NAF1 
               
               
                 6 
                 ENSG00000145491 
                 ROPN1L 
               
               
                 6 
                 ENSG00000145945 
                 FAM50B 
               
               
                 6 
                 ENSG00000145982 
                 FARS2 
               
               
                 6 
                 ENSG00000146038 
                 DCDC2 
               
               
                 6 
                 ENSG00000146083 
                 RNF44 
               
               
                 6 
                 ENSG00000146221 
                 TCTE1 
               
               
                 6 
                 ENSG00000146233 
                 CYP39A1 
               
               
                 6 
                 ENSG00000146242 
                 TPBG 
               
               
                 6 
                 ENSG00000146243 
                 IRAK1BP1 
               
               
                 6 
                 ENSG00000146376 
                 ARHGAP18 
               
               
                 6 
                 ENSG00000146722 
               
               
                 6 
                 ENSG00000146729 
                 GBAS 
               
               
                 6 
                 ENSG00000146733 
                 PSPH 
               
               
                 6 
                 ENSG00000146856 
                 AGBL3 
               
               
                 6 
                 ENSG00000147003 
                 TMEM27 
               
               
                 6 
                 ENSG00000147117 
                 ZNF157 
               
               
                 6 
                 ENSG00000147202 
                 DIAPH2 
               
               
                 6 
                 ENSG00000147224 
                 PRPS1 
               
               
                 6 
                 ENSG00000147231 
                 CXorf57 
               
               
                 6 
                 ENSG00000147316 
                 MCPH1 
               
               
                 6 
                 ENSG00000147400 
                 CETN2 
               
               
                 6 
                 ENSG00000147457 
                 CHMP7 
               
               
                 6 
                 ENSG00000147894 
                 C9orf72 
               
               
                 6 
                 ENSG00000148057 
                 IDNK 
               
               
                 6 
                 ENSG00000148219 
                 ASTN2 
               
               
                 6 
                 ENSG00000148225 
                 WDR31 
               
               
                 6 
                 ENSG00000148660 
                 CAMK2G 
               
               
                 6 
                 ENSG00000148814 
                 LRRC27 
               
               
                 6 
                 ENSG00000148842 
                 CNNM2 
               
               
                 6 
                 ENSG00000149050 
                 ZNF214 
               
               
                 6 
                 ENSG00000149179 
                 C11orf49 
               
               
                 6 
                 ENSG00000149201 
                 CCDC81 
               
               
                 6 
                 ENSG00000149292 
                 TTC12 
               
               
                 6 
                 ENSG00000149300 
                 C11orf52 
               
               
                 6 
                 ENSG00000149328 
                 GLB1L2 
               
               
                 6 
                 ENSG00000149480 
                 MTA2 
               
               
                 6 
                 ENSG00000149573 
                 MPZL2 
               
               
                 6 
                 ENSG00000149782 
                 PLCB3 
               
               
                 6 
                 ENSG00000150281 
                 CTF1 
               
               
                 6 
                 ENSG00000150433 
                 TMEM218 
               
               
                 6 
                 ENSG00000150456 
                 N6AMT2 
               
               
                 6 
                 ENSG00000150628 
                 SPATA4 
               
               
                 6 
                 ENSG00000150667 
                 FSIP1 
               
               
                 6 
                 ENSG00000150764 
                 DIXDC1 
               
               
                 6 
                 ENSG00000150773 
                 PIH1D2 
               
               
                 6 
                 ENSG00000150873 
                 C2orf50 
               
               
                 6 
                 ENSG00000151023 
                 ENKUR 
               
               
                 6 
                 ENSG00000151065 
                 DCP1B 
               
               
                 6 
                 ENSG00000151320 
                 AKAP6 
               
               
                 6 
                 ENSG00000151338 
                 MIPOL1 
               
               
                 6 
                 ENSG00000151413 
                 NUBPL 
               
               
                 6 
                 ENSG00000151445 
                 VIPAS39 
               
               
                 6 
                 ENSG00000151575 
                 TEX9 
               
               
                 6 
                 ENSG00000151689 
                 INPP1 
               
               
                 6 
                 ENSG00000151773 
                 CCDC122 
               
               
                 6 
                 ENSG00000151779 
                 NBAS 
               
               
                 6 
                 ENSG00000152076 
                 CCDC74B 
               
               
                 6 
                 ENSG00000152464 
                 RPP38 
               
               
                 6 
                 ENSG00000152503 
                 TRIM36 
               
               
                 6 
                 ENSG00000152582 
                 SPEF2 
               
               
                 6 
                 ENSG00000152611 
                 CAPSL 
               
               
                 6 
                 ENSG00000152763 
                 WDR78 
               
               
                 6 
                 ENSG00000152936 
                 IFLTD1 
               
               
                 6 
                 ENSG00000153132 
                 CLGN 
               
               
                 6 
                 ENSG00000153140 
                 CETN3 
               
               
                 6 
                 ENSG00000153237 
                 CCDC148 
               
               
                 6 
                 ENSG00000153347 
                 FAM81B 
               
               
                 6 
                 ENSG00000153531 
                 ADPRHL1 
               
               
                 6 
                 ENSG00000153558 
                 FBXL2 
               
               
                 6 
                 ENSG00000153560 
                 UBP1 
               
               
                 6 
                 ENSG00000153714 
                 LURAP1L 
               
               
                 6 
                 ENSG00000153774 
                 CFDP1 
               
               
                 6 
                 ENSG00000153789 
                 FAM92B 
               
               
                 6 
                 ENSG00000153832 
                 FBXO36 
               
               
                 6 
                 ENSG00000153896 
                 ZNF599 
               
               
                 6 
                 ENSG00000153904 
                 DDAH1 
               
               
                 6 
                 ENSG00000153930 
                 ANKFN1 
               
               
                 6 
                 ENSG00000154124 
                 FAM105B 
               
               
                 6 
                 ENSG00000154153 
                 FAM134B 
               
               
                 6 
                 ENSG00000154240 
                 CEP112 
               
               
                 6 
                 ENSG00000154380 
                 ENAH 
               
               
                 6 
                 ENSG00000154479 
                 CCDC173 
               
               
                 6 
                 ENSG00000154556 
                 SORBS2 
               
               
                 6 
                 ENSG00000154760 
                 SLFN13 
               
               
                 6 
                 ENSG00000154917 
                 RAB6B 
               
               
                 6 
                 ENSG00000154930 
                 ACSS1 
               
               
                 6 
                 ENSG00000155026 
                 RSPH10B 
               
               
                 6 
                 ENSG00000155085 
                 AK9 
               
               
                 6 
                 ENSG00000155096 
                 AZIN1 
               
               
                 6 
                 ENSG00000155189 
                 AGPAT5 
               
               
                 6 
                 ENSG00000155530 
                 LRGUK 
               
               
                 6 
                 ENSG00000155666 
                 KDM8 
               
               
                 6 
                 ENSG00000155749 
                 ALS2CR12 
               
               
                 6 
                 ENSG00000155761 
                 SPAG17 
               
               
                 6 
                 ENSG00000155816 
                 FMN2 
               
               
                 6 
                 ENSG00000155974 
                 GRIP1 
               
               
                 6 
                 ENSG00000156030 
                 ELMSAN1 
               
               
                 6 
                 ENSG00000156049 
                 GNA14 
               
               
                 6 
                 ENSG00000156050 
                 FAM161B 
               
               
                 6 
                 ENSG00000156171 
                 DRAM2 
               
               
                 6 
                 ENSG00000156172 
                 C8orf37 
               
               
                 6 
                 ENSG00000156206 
                 C15orf26 
               
               
                 6 
                 ENSG00000156232 
                 WHAMM 
               
               
                 6 
                 ENSG00000156299 
                 TIAM1 
               
               
                 6 
                 ENSG00000156313 
                 RPGR 
               
               
                 6 
                 ENSG00000156463 
                 SH3RF2 
               
               
                 6 
                 ENSG00000156958 
                 GALK2 
               
               
                 6 
                 ENSG00000157227 
                 MMP14 
               
               
                 6 
                 ENSG00000157330 
                 C1orf158 
               
               
                 6 
                 ENSG00000157423 
                 HYDIN 
               
               
                 6 
                 ENSG00000157429 
                 ZNF19 
               
               
                 6 
                 ENSG00000157470 
                 FAM81A 
               
               
                 6 
                 ENSG00000157538 
                 DSCR3 
               
               
                 6 
                 ENSG00000157578 
                 LCA5L 
               
               
                 6 
                 ENSG00000157653 
                 C9orf43 
               
               
                 6 
                 ENSG00000157796 
                 WDR19 
               
               
                 6 
                 ENSG00000157856 
                 DRC1 
               
               
                 6 
                 ENSG00000157869 
                 RAB28 
               
               
                 6 
                 ENSG00000158023 
                 WDR66 
               
               
                 6 
                 ENSG00000158113 
                 LRRC43 
               
               
                 6 
                 ENSG00000158122 
                 AAED1 
               
               
                 6 
                 ENSG00000158234 
                 FAIM 
               
               
                 6 
                 ENSG00000158296 
                 SLC13A3 
               
               
                 6 
                 ENSG00000158423 
                 RIBC1 
               
               
                 6 
                 ENSG00000158428 
                 C2orf62 
               
               
                 6 
                 ENSG00000158445 
                 KCNB1 
               
               
                 6 
                 ENSG00000158486 
                 DNAH3 
               
               
                 6 
                 ENSG00000158669 
                 AGPAT6 
               
               
                 6 
                 ENSG00000158850 
                 B4GALT3 
               
               
                 6 
                 ENSG00000159079 
                 C21orf59 
               
               
                 6 
                 ENSG00000159239 
                 C2orf81 
               
               
                 6 
                 ENSG00000159685 
                 CHCHD6 
               
               
                 6 
                 ENSG00000159713 
                 TPPP3 
               
               
                 6 
                 ENSG00000159714 
                 ZDHHC1 
               
               
                 6 
                 ENSG00000160051 
                 IQCC 
               
               
                 6 
                 ENSG00000160145 
                 KALRN 
               
               
                 6 
                 ENSG00000160183 
                 TMPRSS3 
               
               
                 6 
                 ENSG00000160188 
                 RSPH1 
               
               
                 6 
                 ENSG00000160345 
                 C9orf116 
               
               
                 6 
                 ENSG00000160613 
                 PCSK7 
               
               
                 6 
                 ENSG00000160753 
                 RUSC1 
               
               
                 6 
                 ENSG00000160803 
                 UBQLN4 
               
               
                 6 
                 ENSG00000160949 
                 TONSL 
               
               
                 6 
                 ENSG00000160991 
                 ORAI2 
               
               
                 6 
                 ENSG00000161036 
                 LRWD1 
               
               
                 6 
                 ENSG00000161040 
                 FBXL13 
               
               
                 6 
                 ENSG00000161326 
                 DUSP14 
               
               
                 6 
                 ENSG00000161328 
                 LRRC56 
               
               
                 6 
                 ENSG00000161513 
                 FDXR 
               
               
                 6 
                 ENSG00000161905 
                 ALOX15 
               
               
                 6 
                 ENSG00000162040 
                 HS3ST6 
               
               
                 6 
                 ENSG00000162105 
                 SHANK2 
               
               
                 6 
                 ENSG00000162148 
                 PPP1R32 
               
               
                 6 
                 ENSG00000162302 
                 RPS6KA4 
               
               
                 6 
                 ENSG00000162543 
                 UBXN10 
               
               
                 6 
                 ENSG00000162598 
                 C1orf87 
               
               
                 6 
                 ENSG00000162600 
                 OMA1 
               
               
                 6 
                 ENSG00000162616 
                 DNAJB4 
               
               
                 6 
                 ENSG00000162620 
                 LRRIQ3 
               
               
                 6 
                 ENSG00000162643 
                 WDR63 
               
               
                 6 
                 ENSG00000162755 
                 KLHDC9 
               
               
                 6 
                 ENSG00000162769 
                 FLVCR1 
               
               
                 6 
                 ENSG00000162814 
                 SPATA17 
               
               
                 6 
                 ENSG00000162999 
                 DUSP19 
               
               
                 6 
                 ENSG00000163001 
                 CCDC104 
               
               
                 6 
                 ENSG00000163006 
                 CCDC138 
               
               
                 6 
                 ENSG00000163040 
                 CCDC74A 
               
               
                 6 
                 ENSG00000163060 
                 TEKT4 
               
               
                 6 
                 ENSG00000163071 
                 SPATA18 
               
               
                 6 
                 ENSG00000163075 
               
               
                 6 
                 ENSG00000163083 
                 INHBB 
               
               
                 6 
                 ENSG00000163093 
                 BBS5 
               
               
                 6 
                 ENSG00000163125 
                 RPRD2 
               
               
                 6 
                 ENSG00000163138 
                 PACRGL 
               
               
                 6 
                 ENSG00000163214 
                 DHX57 
               
               
                 6 
                 ENSG00000163251 
                 FZD5 
               
               
                 6 
                 ENSG00000163263 
                 C1orf189 
               
               
                 6 
                 ENSG00000163322 
                 FAM175A 
               
               
                 6 
                 ENSG00000163349 
                 HIPK1 
               
               
                 6 
                 ENSG00000163491 
                 NEK10 
               
               
                 6 
                 ENSG00000163512 
                 AZI2 
               
               
                 6 
                 ENSG00000163521 
                 GLB1L 
               
               
                 6 
                 ENSG00000163576 
                 EFHB 
               
               
                 6 
                 ENSG00000163596 
                 ICA1L 
               
               
                 6 
                 ENSG00000163617 
                 KIAA1407 
               
               
                 6 
                 ENSG00000163624 
                 CDS1 
               
               
                 6 
                 ENSG00000163655 
                 GMPS 
               
               
                 6 
                 ENSG00000163686 
                 ABHD6 
               
               
                 6 
                 ENSG00000163818 
                 LZTFL1 
               
               
                 6 
                 ENSG00000163875 
                 MEAF6 
               
               
                 6 
                 ENSG00000163879 
                 DNALI1 
               
               
                 6 
                 ENSG00000164002 
                 EXO5 
               
               
                 6 
                 ENSG00000164099 
                 PRSS12 
               
               
                 6 
                 ENSG00000164114 
                 MAP9 
               
               
                 6 
                 ENSG00000164118 
                 CEP44 
               
               
                 6 
                 ENSG00000164185 
                 ZNF474 
               
               
                 6 
                 ENSG00000164306 
                 PRIMPOL 
               
               
                 6 
                 ENSG00000164402 
                 8-Sep 
               
               
                 6 
                 ENSG00000164404 
                 GDF9 
               
               
                 6 
                 ENSG00000164411 
                 GJB7 
               
               
                 6 
                 ENSG00000164440 
                 TXLNB 
               
               
                 6 
                 ENSG00000164465 
                 DCBLD1 
               
               
                 6 
                 ENSG00000164542 
                 KIAA0895 
               
               
                 6 
                 ENSG00000164627 
                 KIF6 
               
               
                 6 
                 ENSG00000164674 
                 SYTL3 
               
               
                 6 
                 ENSG00000164675 
                 IQUB 
               
               
                 6 
                 ENSG00000164746 
                 C7orf57 
               
               
                 6 
                 ENSG00000164758 
                 MED30 
               
               
                 6 
                 ENSG00000164818 
                 HEATR2 
               
               
                 6 
                 ENSG00000164938 
                 TP53INP1 
               
               
                 6 
                 ENSG00000164953 
                 TMEM67 
               
               
                 6 
                 ENSG00000164970 
                 FAM219A 
               
               
                 6 
                 ENSG00000164972 
                 C9orf24 
               
               
                 6 
                 ENSG00000165029 
                 ABCA1 
               
               
                 6 
                 ENSG00000165084 
                 C8orf34 
               
               
                 6 
                 ENSG00000165097 
                 KDM1B 
               
               
                 6 
                 ENSG00000165118 
                 C9orf64 
               
               
                 6 
                 ENSG00000165124 
                 SVEP1 
               
               
                 6 
                 ENSG00000165164 
                 CXorf22 
               
               
                 6 
                 ENSG00000165185 
                 KIAA1958 
               
               
                 6 
                 ENSG00000165209 
                 STRBP 
               
               
                 6 
                 ENSG00000165219 
                 GAPVD1 
               
               
                 6 
                 ENSG00000165309 
                 ARMC3 
               
               
                 6 
                 ENSG00000165383 
                 LRRC18 
               
               
                 6 
                 ENSG00000165506 
                 DNAAF2 
               
               
                 6 
                 ENSG00000165533 
                 TTC8 
               
               
                 6 
                 ENSG00000165695 
                 AK8 
               
               
                 6 
                 ENSG00000165698 
                 C9orf9 
               
               
                 6 
                 ENSG00000165724 
                 ZMYND19 
               
               
                 6 
                 ENSG00000165730 
                 STOX1 
               
               
                 6 
                 ENSG00000165807 
                 PPP1R36 
               
               
                 6 
                 ENSG00000166165 
                 CKB 
               
               
                 6 
                 ENSG00000166171 
                 DPCD 
               
               
                 6 
                 ENSG00000166173 
                 LARP6 
               
               
                 6 
                 ENSG00000166246 
                 C16orf71 
               
               
                 6 
                 ENSG00000166262 
                 FAM227B 
               
               
                 6 
                 ENSG00000166263 
                 STXBP4 
               
               
                 6 
                 ENSG00000166275 
                 C10orf32 
               
               
                 6 
                 ENSG00000166311 
                 SMPD1 
               
               
                 6 
                 ENSG00000166313 
                 APBB1 
               
               
                 6 
                 ENSG00000166323 
                 C11orf65 
               
               
                 6 
                 ENSG00000166352 
                 C11orf74 
               
               
                 6 
                 ENSG00000166402 
                 TUB 
               
               
                 6 
                 ENSG00000166435 
                 XRRA1 
               
               
                 6 
                 ENSG00000166455 
                 C16orf46 
               
               
                 6 
                 ENSG00000166526 
                 ZNF3 
               
               
                 6 
                 ENSG00000166578 
                 IQCD 
               
               
                 6 
                 ENSG00000166592 
                 RRAD 
               
               
                 6 
                 ENSG00000166596 
                 WDR16 
               
               
                 6 
                 ENSG00000166946 
                 CCNDBP1 
               
               
                 6 
                 ENSG00000166959 
                 MS4A8 
               
               
                 6 
                 ENSG00000166963 
                 MAP1A 
               
               
                 6 
                 ENSG00000167065 
                 DUSP18 
               
               
                 6 
                 ENSG00000167094 
                 TTC16 
               
               
                 6 
                 ENSG00000167113 
                 COQ4 
               
               
                 6 
                 ENSG00000167131 
                 CCDC103 
               
               
                 6 
                 ENSG00000167136 
                 ENDOG 
               
               
                 6 
                 ENSG00000167186 
                 COQ7 
               
               
                 6 
                 ENSG00000167216 
                 KATNAL2 
               
               
                 6 
                 ENSG00000167523 
                 SPATA33 
               
               
                 6 
                 ENSG00000167550 
                 RHEBL1 
               
               
                 6 
                 ENSG00000167552 
                 TUBA1A 
               
               
                 6 
                 ENSG00000167646 
                 DNAAF3 
               
               
                 6 
                 ENSG00000167733 
                 HSD11B1L 
               
               
                 6 
                 ENSG00000167740 
                 CYB5D2 
               
               
                 6 
                 ENSG00000167858 
                 TEKT1 
               
               
                 6 
                 ENSG00000167904 
                 TMEM68 
               
               
                 6 
                 ENSG00000167962 
                 ZNF598 
               
               
                 6 
                 ENSG00000168014 
                 C2CD3 
               
               
                 6 
                 ENSG00000168038 
                 ULK4 
               
               
                 6 
                 ENSG00000168314 
                 MOBP 
               
               
                 6 
                 ENSG00000168350 
                 DEGS2 
               
               
                 6 
                 ENSG00000168487 
                 BMP1 
               
               
                 6 
                 ENSG00000168575 
                 SLC20A2 
               
               
                 6 
                 ENSG00000168589 
                 DYNLRB2 
               
               
                 6 
                 ENSG00000168658 
                 VWA3B 
               
               
                 6 
                 ENSG00000168675 
                 LDLRAD4 
               
               
                 6 
                 ENSG00000168734 
                 PKIG 
               
               
                 6 
                 ENSG00000168754 
                 FAM178B 
               
               
                 6 
                 ENSG00000168772 
                 CXXC4 
               
               
                 6 
                 ENSG00000168778 
                 TCTN2 
               
               
                 6 
                 ENSG00000168884 
                 TNIP2 
               
               
                 6 
                 ENSG00000168938 
                 PPIC 
               
               
                 6 
                 ENSG00000169064 
                 ZBBX 
               
               
                 6 
                 ENSG00000169126 
                 ARMC4 
               
               
                 6 
                 ENSG00000169189 
                 NSMCE1 
               
               
                 6 
                 ENSG00000169213 
                 RAB3B 
               
               
                 6 
                 ENSG00000169379 
                 ARL13B 
               
               
                 6 
                 ENSG00000169550 
                 MUC15 
               
               
                 6 
                 ENSG00000169902 
                 TPST1 
               
               
                 6 
                 ENSG00000169905 
                 TOR1AIP2 
               
               
                 6 
                 ENSG00000170231 
                 FABP6 
               
               
                 6 
                 ENSG00000170264 
                 FAM161A 
               
               
                 6 
                 ENSG00000170270 
                 C14orf142 
               
               
                 6 
                 ENSG00000170469 
                 SPATA24 
               
               
                 6 
                 ENSG00000170482 
                 SLC23A1 
               
               
                 6 
                 ENSG00000170509 
                 HSD17B13 
               
               
                 6 
                 ENSG00000170871 
                 KIAA0232 
               
               
                 6 
                 ENSG00000170959 
                 DCDC1 
               
               
                 6 
                 ENSG00000171132 
                 PRKCE 
               
               
                 6 
                 ENSG00000171160 
                 MORN4 
               
               
                 6 
                 ENSG00000171174 
                 RBKS 
               
               
                 6 
                 ENSG00000171428 
                 NAT1 
               
               
                 6 
                 ENSG00000171517 
                 LPAR3 
               
               
                 6 
                 ENSG00000171533 
                 MAP6 
               
               
                 6 
                 ENSG00000171574 
                 ZNF584 
               
               
                 6 
                 ENSG00000171595 
                 DNAI2 
               
               
                 6 
                 ENSG00000171757 
                 LRRC34 
               
               
                 6 
                 ENSG00000171793 
                 CTPS1 
               
               
                 6 
                 ENSG00000171798 
                 KNDC1 
               
               
                 6 
                 ENSG00000171885 
                 AQP4 
               
               
                 6 
                 ENSG00000171962 
                 LRRC48 
               
               
                 6 
                 ENSG00000172164 
                 SNTB1 
               
               
                 6 
                 ENSG00000172301 
                 COPRS 
               
               
                 6 
                 ENSG00000172361 
                 CCDC11 
               
               
                 6 
                 ENSG00000172426 
                 RSPH9 
               
               
                 6 
                 ENSG00000172578 
                 KLHL6 
               
               
                 6 
                 ENSG00000172671 
                 ZFAND4 
               
               
                 6 
                 ENSG00000172955 
                 ADH6 
               
               
                 6 
                 ENSG00000173013 
                 CCDC96 
               
               
                 6 
                 ENSG00000173208 
                 ABCD2 
               
               
                 6 
                 ENSG00000173226 
                 IQCB1 
               
               
                 6 
                 ENSG00000173627 
                 APOBEC4 
               
               
                 6 
                 ENSG00000173838 
                 10-Mar 
               
               
                 6 
                 ENSG00000173947 
                 PIFO 
               
               
                 6 
                 ENSG00000174007 
                 CEP19 
               
               
                 6 
                 ENSG00000174132 
                 FAM174A 
               
               
                 6 
                 ENSG00000174156 
                 GSTA3 
               
               
                 6 
                 ENSG00000174343 
                 CHRNA9 
               
               
                 6 
                 ENSG00000174456 
                 C12orf76 
               
               
                 6 
                 ENSG00000174483 
                 BBS1 
               
               
                 6 
                 ENSG00000174586 
                 ZNF497 
               
               
                 6 
                 ENSG00000174628 
                 IQCK 
               
               
                 6 
                 ENSG00000174705 
                 SH3PXD2B 
               
               
                 6 
                 ENSG00000174776 
                 WDR49 
               
               
                 6 
                 ENSG00000174796 
                 THAP6 
               
               
                 6 
                 ENSG00000174808 
                 BTC 
               
               
                 6 
                 ENSG00000174898 
                 CATSPERD 
               
               
                 6 
                 ENSG00000175279 
                 APITD1 
               
               
                 6 
                 ENSG00000175376 
                 EIF1AD 
               
               
                 6 
                 ENSG00000175664 
                 TEX26 
               
               
                 6 
                 ENSG00000175697 
                 GPR156 
               
               
                 6 
                 ENSG00000175792 
                 RUVBL1 
               
               
                 6 
                 ENSG00000175970 
                 UNC119B 
               
               
                 6 
                 ENSG00000176040 
                 TMPRSS7 
               
               
                 6 
                 ENSG00000176171 
                 BNIP3 
               
               
                 6 
                 ENSG00000176209 
                 SMIM19 
               
               
                 6 
                 ENSG00000176381 
                 PRR18 
               
               
                 6 
                 ENSG00000176401 
                 EID2B 
               
               
                 6 
                 ENSG00000176485 
                 PLA2G16 
               
               
                 6 
                 ENSG00000176563 
                 CNTD1 
               
               
                 6 
                 ENSG00000176601 
                 MAP3K19 
               
               
                 6 
                 ENSG00000176714 
                 CCDC121 
               
               
                 6 
                 ENSG00000176986 
                 SEC24C 
               
               
                 6 
                 ENSG00000177103 
                 DSCAML1 
               
               
                 6 
                 ENSG00000177112 
                 MRVI1-AS1 
               
               
                 6 
                 ENSG00000177398 
                 UMODL1 
               
               
                 6 
                 ENSG00000177459 
                 C8orf47 
               
               
                 6 
                 ENSG00000177508 
                 IRX3 
               
               
                 6 
                 ENSG00000177640 
                 CASC2 
               
               
                 6 
                 ENSG00000177674 
                 AGTRAP 
               
               
                 6 
                 ENSG00000177994 
                 C2orf73 
               
               
                 6 
                 ENSG00000178053 
                 MLF1 
               
               
                 6 
                 ENSG00000178075 
                 GRAMD1C 
               
               
                 6 
                 ENSG00000178125 
                 PPP1R42 
               
               
                 6 
                 ENSG00000178149 
                 DALRD3 
               
               
                 6 
                 ENSG00000178425 
                 NT5DC1 
               
               
                 6 
                 ENSG00000178460 
                 MCMDC2 
               
               
                 6 
                 ENSG00000178467 
                 P4HTM 
               
               
                 6 
                 ENSG00000178568 
                 ERBB4 
               
               
                 6 
                 ENSG00000178665 
                 ZNF713 
               
               
                 6 
                 ENSG00000178732 
                 GP5 
               
               
                 6 
                 ENSG00000178796 
                 RIIAD1 
               
               
                 6 
                 ENSG00000178965 
                 C1orf173 
               
               
                 6 
                 ENSG00000179029 
                 TMEM107 
               
               
                 6 
                 ENSG00000179071 
                 CCDC89 
               
               
                 6 
                 ENSG00000179133 
                 C10orf67 
               
               
                 6 
                 ENSG00000179195 
                 ZNF664 
               
               
                 6 
                 ENSG00000179240 
               
               
                 6 
                 ENSG00000179598 
                 PLD6 
               
               
                 6 
                 ENSG00000179813 
                 FAM216B 
               
               
                 6 
                 ENSG00000179902 
                 C1orf194 
               
               
                 6 
                 ENSG00000180098 
                 TRNAU1AP 
               
               
                 6 
                 ENSG00000180263 
                 FGD6 
               
               
                 6 
                 ENSG00000180346 
                 TIGD2 
               
               
                 6 
                 ENSG00000180481 
                 GLIPR1L2 
               
               
                 6 
                 ENSG00000180509 
                 KCNE1 
               
               
                 6 
                 ENSG00000180769 
                 WDFY3-AS2 
               
               
                 6 
                 ENSG00000180787 
                 ZFP3 
               
               
                 6 
                 ENSG00000180914 
                 OXTR 
               
               
                 6 
                 ENSG00000181004 
                 BBS12 
               
               
                 6 
                 ENSG00000181322 
                 NME9 
               
               
                 6 
                 ENSG00000181481 
                 RNF135 
               
               
                 6 
                 ENSG00000181619 
                 GPR135 
               
               
                 6 
                 ENSG00000182093 
                 WRB 
               
               
                 6 
                 ENSG00000182224 
                 CYB5D1 
               
               
                 6 
                 ENSG00000182329 
               
               
                 6 
                 ENSG00000182504 
                 CEP97 
               
               
                 6 
                 ENSG00000182518 
                 FAM104B 
               
               
                 6 
                 ENSG00000182768 
                 NGRN 
               
               
                 6 
                 ENSG00000182957 
                 SPATA13 
               
               
                 6 
                 ENSG00000183117 
                 CSMD1 
               
               
                 6 
                 ENSG00000183161 
                 FANCF 
               
               
                 6 
                 ENSG00000183207 
                 RUVBL2 
               
               
                 6 
                 ENSG00000183273 
                 CCDC60 
               
               
                 6 
                 ENSG00000183323 
                 CCDC125 
               
               
                 6 
                 ENSG00000183346 
                 C10orf107 
               
               
                 6 
                 ENSG00000183578 
                 TNFAIP8L3 
               
               
                 6 
                 ENSG00000183628 
                 DGCR6 
               
               
                 6 
                 ENSG00000183644 
                 C11orf88 
               
               
                 6 
                 ENSG00000183690 
                 EFHC2 
               
               
                 6 
                 ENSG00000183784 
                 C9orf66 
               
               
                 6 
                 ENSG00000183826 
                 BTBD9 
               
               
                 6 
                 ENSG00000183831 
                 ANKRD45 
               
               
                 6 
                 ENSG00000183914 
                 DNAH2 
               
               
                 6 
                 ENSG00000183941 
                 HIST2H4A 
               
               
                 6 
                 ENSG00000184154 
                 LRTOMT 
               
               
                 6 
                 ENSG00000184349 
                 EFNA5 
               
               
                 6 
                 ENSG00000184385 
                 C21orf128 
               
               
                 6 
                 ENSG00000184500 
                 PROS1 
               
               
                 6 
                 ENSG00000184613 
                 NELL2 
               
               
                 6 
                 ENSG00000184702 
                 5-Sep 
               
               
                 6 
                 ENSG00000184731 
                 FAM110C 
               
               
                 6 
                 ENSG00000184886 
                 PIGW 
               
               
                 6 
                 ENSG00000184898 
                 RBM43 
               
               
                 6 
                 ENSG00000184939 
                 ZFP90 
               
               
                 6 
                 ENSG00000184986 
                 TMEM121 
               
               
                 6 
                 ENSG00000185055 
                 EFCAB10 
               
               
                 6 
                 ENSG00000185158 
                 LRRC37B 
               
               
                 6 
                 ENSG00000185220 
                 PGBD2 
               
               
                 6 
                 ENSG00000185222 
                 WBP5 
               
               
                 6 
                 ENSG00000185250 
                 PPIL6 
               
               
                 6 
                 ENSG00000185261 
                 KIAA0825 
               
               
                 6 
                 ENSG00000185267 
                 CDNF 
               
               
                 6 
                 ENSG00000185305 
                 ARL15 
               
               
                 6 
                 ENSG00000185361 
                 TNFAIP8L1 
               
               
                 6 
                 ENSG00000185379 
                 RAD51D 
               
               
                 6 
                 ENSG00000185420 
                 SMYD3 
               
               
                 6 
                 ENSG00000185608 
                 MRPL40 
               
               
                 6 
                 ENSG00000185681 
                 MORN5 
               
               
                 6 
                 ENSG00000185875 
                 THNSL1 
               
               
                 6 
                 ENSG00000185989 
                 RASA3 
               
               
                 6 
                 ENSG00000186094 
                 AGBL4 
               
               
                 6 
                 ENSG00000186104 
                 CYP2R1 
               
               
                 6 
                 ENSG00000186132 
                 C2orf76 
               
               
                 6 
                 ENSG00000186198 
                 SLC51B 
               
               
                 6 
                 ENSG00000186231 
                 KLHL32 
               
               
                 6 
                 ENSG00000186314 
                 PRELID2 
               
               
                 6 
                 ENSG00000186329 
                 TMEM212 
               
               
                 6 
                 ENSG00000186352 
                 ANKRD37 
               
               
                 6 
                 ENSG00000186471 
                 AKAP14 
               
               
                 6 
                 ENSG00000186496 
                 ZNF396 
               
               
                 6 
                 ENSG00000186523 
                 FAM86B1 
               
               
                 6 
                 ENSG00000186625 
                 KATNA1 
               
               
                 6 
                 ENSG00000186638 
                 KIF24 
               
               
                 6 
                 ENSG00000186687 
                 LYRM7 
               
               
                 6 
                 ENSG00000186889 
                 TMEM17 
               
               
                 6 
                 ENSG00000186952 
                 TMEM232 
               
               
                 6 
                 ENSG00000186973 
                 FAM183A 
               
               
                 6 
                 ENSG00000186976 
                 EFCAB6 
               
               
                 6 
                 ENSG00000187079 
                 TEAD1 
               
               
                 6 
                 ENSG00000187122 
                 SLIT1 
               
               
                 6 
                 ENSG00000187189 
                 TSPYL4 
               
               
                 6 
                 ENSG00000187240 
                 DYNC2H1 
               
               
                 6 
                 ENSG00000187260 
                 WDR86 
               
               
                 6 
                 ENSG00000187535 
                 IFT140 
               
               
                 6 
                 ENSG00000187624 
                 C17orf97 
               
               
                 6 
                 ENSG00000187642 
                 C1orf170 
               
               
                 6 
                 ENSG00000187695 
               
               
                 6 
                 ENSG00000187726 
                 DNAJB13 
               
               
                 6 
                 ENSG00000187733 
                 AMY1C 
               
               
                 6 
                 ENSG00000188010 
                 MORN2 
               
               
                 6 
                 ENSG00000188039 
                 NWD1 
               
               
                 6 
                 ENSG00000188229 
                 TUBB4B 
               
               
                 6 
                 ENSG00000188316 
                 ENO4 
               
               
                 6 
                 ENSG00000188352 
                 FOCAD 
               
               
                 6 
                 ENSG00000188396 
                 TCTEX1D4 
               
               
                 6 
                 ENSG00000188452 
                 CERKL 
               
               
                 6 
                 ENSG00000188523 
                 C9orf171 
               
               
                 6 
                 ENSG00000188596 
                 C12orf55 
               
               
                 6 
                 ENSG00000188659 
                 FAM154B 
               
               
                 6 
                 ENSG00000188817 
                 SNTN 
               
               
                 6 
                 ENSG00000188921 
                 PTPLAD2 
               
               
                 6 
                 ENSG00000188931 
                 C1orf192 
               
               
                 6 
                 ENSG00000189157 
                 FAM47E 
               
               
                 6 
                 ENSG00000196090 
                 PTPRT 
               
               
                 6 
                 ENSG00000196169 
                 KIF19 
               
               
                 6 
                 ENSG00000196230 
                 TUBB 
               
               
                 6 
                 ENSG00000196236 
                 XPNPEP3 
               
               
                 6 
                 ENSG00000196277 
                 GRM7 
               
               
                 6 
                 ENSG00000196437 
                 ZNF569 
               
               
                 6 
                 ENSG00000196476 
                 C20orf96 
               
               
                 6 
                 ENSG00000196482 
                 ESRRG 
               
               
                 6 
                 ENSG00000196535 
                 MYO18A 
               
               
                 6 
                 ENSG00000196659 
                 TTC30B 
               
               
                 6 
                 ENSG00000196693 
                 ZNF33B 
               
               
                 6 
                 ENSG00000196704 
                 AMZ2 
               
               
                 6 
                 ENSG00000196814 
                 MVB12B 
               
               
                 6 
                 ENSG00000196872 
                 KIAA1211L 
               
               
                 6 
                 ENSG00000196890 
                 HIST3H2BB 
               
               
                 6 
                 ENSG00000197057 
                 DTHD1 
               
               
                 6 
                 ENSG00000197122 
                 SRC 
               
               
                 6 
                 ENSG00000197168 
                 NEK5 
               
               
                 6 
                 ENSG00000197208 
                 SLC22A4 
               
               
                 6 
                 ENSG00000197580 
                 BCO2 
               
               
                 6 
                 ENSG00000197584 
                 KCNMB2 
               
               
                 6 
                 ENSG00000197603 
                 C5orf42 
               
               
                 6 
                 ENSG00000197653 
                 DNAH10 
               
               
                 6 
                 ENSG00000197748 
                 WDR96 
               
               
                 6 
                 ENSG00000197826 
                 C4orf22 
               
               
                 6 
                 ENSG00000197889 
                 MEIG1 
               
               
                 6 
                 ENSG00000197980 
                 LEKR1 
               
               
                 6 
                 ENSG00000198003 
                 CCDC151 
               
               
                 6 
                 ENSG00000198088 
                 NUP62CL 
               
               
                 6 
                 ENSG00000198125 
                 MB 
               
               
                 6 
                 ENSG00000198157 
                 HMGN5 
               
               
                 6 
                 ENSG00000198182 
                 ZNF607 
               
               
                 6 
                 ENSG00000198551 
                 ZNF627 
               
               
                 6 
                 ENSG00000198553 
                 KCNRG 
               
               
                 6 
                 ENSG00000198624 
                 CCDC69 
               
               
                 6 
                 ENSG00000198668 
                 CALM1 
               
               
                 6 
                 ENSG00000198718 
                 FAM179B 
               
               
                 6 
                 ENSG00000198729 
                 PPP1R14C 
               
               
                 6 
                 ENSG00000198815 
                 FOXJ3 
               
               
                 6 
                 ENSG00000198825 
                 INPP5F 
               
               
                 6 
                 ENSG00000198860 
                 TSEN15 
               
               
                 6 
                 ENSG00000198894 
                 CIPC 
               
               
                 6 
                 ENSG00000198919 
                 DZIP3 
               
               
                 6 
                 ENSG00000198945 
                 L3MBTL3 
               
               
                 6 
                 ENSG00000198947 
                 DMD 
               
               
                 6 
                 ENSG00000198960 
                 ARMCX6 
               
               
                 6 
                 ENSG00000203301 
               
               
                 6 
                 ENSG00000203372 
               
               
                 6 
                 ENSG00000203485 
                 INF2 
               
               
                 6 
                 ENSG00000203499 
                 FAM83H-AS1 
               
               
                 6 
                 ENSG00000203666 
                 EFCAB2 
               
               
                 6 
                 ENSG00000203705 
                 TATDN3 
               
               
                 6 
                 ENSG00000203734 
                 ECT2L 
               
               
                 6 
                 ENSG00000203778 
                 FAM229B 
               
               
                 6 
                 ENSG00000203797 
                 DDO 
               
               
                 6 
                 ENSG00000203865 
                 ATP1A1OS 
               
               
                 6 
                 ENSG00000203965 
                 EFCAB7 
               
               
                 6 
                 ENSG00000203985 
                 LDLRAD1 
               
               
                 6 
                 ENSG00000204052 
                 LRRC73 
               
               
                 6 
                 ENSG00000204070 
                 SYS1 
               
               
                 6 
                 ENSG00000204104 
                 TRAF3IP1 
               
               
                 6 
                 ENSG00000204356 
                 NELFE 
               
               
                 6 
                 ENSG00000204390 
                 HSPA1L 
               
               
                 6 
                 ENSG00000204428 
                 LY6G5C 
               
               
                 6 
                 ENSG00000204438 
                 GPANK1 
               
               
                 6 
                 ENSG00000204566 
                 C10orf115 
               
               
                 6 
                 ENSG00000204599 
                 TRIM39 
               
               
                 6 
                 ENSG00000204666 
               
               
                 6 
                 ENSG00000204682 
                 CASC10 
               
               
                 6 
                 ENSG00000204711 
                 C9orf135 
               
               
                 6 
                 ENSG00000204815 
                 TTC25 
               
               
                 6 
                 ENSG00000204852 
                 TCTN1 
               
               
                 6 
                 ENSG00000204860 
                 FAM201A 
               
               
                 6 
                 ENSG00000204950 
                 LRRC10B 
               
               
                 6 
                 ENSG00000205084 
                 TMEM231 
               
               
                 6 
                 ENSG00000205129 
                 C4orf47 
               
               
                 6 
                 ENSG00000205231 
                 TTLL10-AS1 
               
               
                 6 
                 ENSG00000205240 
                 OR7E36P 
               
               
                 6 
                 ENSG00000205593 
                 DENND6B 
               
               
                 6 
                 ENSG00000205730 
                 ITPRIPL2 
               
               
                 6 
                 ENSG00000205758 
                 CRYZL1 
               
               
                 6 
                 ENSG00000205808 
                 PPAPDC2 
               
               
                 6 
                 ENSG00000205930 
                 C21orf49 
               
               
                 6 
                 ENSG00000206053 
                 HN1L 
               
               
                 6 
                 ENSG00000206199 
                 ANKUB1 
               
               
                 6 
                 ENSG00000206567 
               
               
                 6 
                 ENSG00000213085 
                 CCDC19 
               
               
                 6 
                 ENSG00000213123 
                 TCTEX1D2 
               
               
                 6 
                 ENSG00000213297 
                 ZNF625- 
               
               
                   
                   
                 ZNF20 
               
               
                 6 
                 ENSG00000213533 
                 TMEM110 
               
               
                 6 
                 ENSG00000213753 
                 CENPBD1P1 
               
               
                 6 
                 ENSG00000213904 
                 LIPE-AS1 
               
               
                 6 
                 ENSG00000213937 
                 CLDN9 
               
               
                 6 
                 ENSG00000214114 
                 MYCBP 
               
               
                 6 
                 ENSG00000214174 
                 AMZ2P1 
               
               
                 6 
                 ENSG00000214413 
                 BBIP1 
               
               
                 6 
                 ENSG00000214447 
                 FAM187A 
               
               
                 6 
                 ENSG00000214575 
                 CPEB1 
               
               
                 6 
                 ENSG00000214706 
                 IFRD2 
               
               
                 6 
                 ENSG00000215187 
                 FAM166B 
               
               
                 6 
                 ENSG00000215217 
                 C5orf49 
               
               
                 6 
                 ENSG00000215475 
                 SIAH3 
               
               
                 6 
                 ENSG00000215845 
                 TSTD1 
               
               
                 6 
                 ENSG00000219626 
                 FAM228B 
               
               
                 6 
                 ENSG00000221821 
                 C6orf226 
               
               
                 6 
                 ENSG00000221838 
                 AP4M1 
               
               
                 6 
                 ENSG00000221995 
                 TIAF1 
               
               
                 6 
                 ENSG00000222046 
                 DCDC2B 
               
               
                 6 
                 ENSG00000223343 
               
               
                 6 
                 ENSG00000223547 
                 ZNF844 
               
               
                 6 
                 ENSG00000223658 
               
               
                 6 
                 ENSG00000224038 
               
               
                 6 
                 ENSG00000224049 
               
               
                 6 
                 ENSG00000224165 
                 DNAJC27- 
               
               
                   
                   
                 AS1 
               
               
                 6 
                 ENSG00000224281 
                 SLC25A5-AS1 
               
               
                 6 
                 ENSG00000224479 
               
               
                 6 
                 ENSG00000224699 
                 LAMTOR5- 
               
               
                   
                   
                 AS1 
               
               
                 6 
                 ENSG00000225302 
               
               
                 6 
                 ENSG00000225361 
                 PPP1R26-AS1 
               
               
                 6 
                 ENSG00000225377 
               
               
                 6 
                 ENSG00000225431 
               
               
                 6 
                 ENSG00000225766 
               
               
                 6 
                 ENSG00000226026 
               
               
                 6 
                 ENSG00000226137 
                 BAIAP2-AS1 
               
               
                 6 
                 ENSG00000226471 
               
               
                 6 
                 ENSG00000226644 
               
               
                 6 
                 ENSG00000226711 
                 FAM66C 
               
               
                 6 
                 ENSG00000226754 
               
               
                 6 
                 ENSG00000227084 
               
               
                 6 
                 ENSG00000227308 
               
               
                 6 
                 ENSG00000227630 
                 LINC01132 
               
               
                 6 
                 ENSG00000227695 
                 DNMBP-AS1 
               
               
                 6 
                 ENSG00000227877 
                 LINC00948 
               
               
                 6 
                 ENSG00000228084 
               
               
                 6 
                 ENSG00000228242 
               
               
                 6 
                 ENSG00000228723 
                 SRGAP3-AS2 
               
               
                 6 
                 ENSG00000228858 
               
               
                 6 
                 ENSG00000228889 
                 UBAC2-AS1 
               
               
                 6 
                 ENSG00000229124 
                 VIM-AS1 
               
               
                 6 
                 ENSG00000229980 
                 TOB1-AS1 
               
               
                 6 
                 ENSG00000230062 
                 ANKRD66 
               
               
                 6 
                 ENSG00000230873 
                 STMND1 
               
               
                 6 
                 ENSG00000230943 
               
               
                 6 
                 ENSG00000231023 
                 LINC00326 
               
               
                 6 
                 ENSG00000231028 
                 LINC00271 
               
               
                 6 
                 ENSG00000231043 
               
               
                 6 
                 ENSG00000231621 
               
               
                 6 
                 ENSG00000231738 
                 TSPAN19 
               
               
                 6 
                 ENSG00000231980 
               
               
                 6 
                 ENSG00000232415 
               
               
                 6 
                 ENSG00000232453 
               
               
                 6 
                 ENSG00000232859 
                 LYRM9 
               
               
                 6 
                 ENSG00000232862 
               
               
                 6 
                 ENSG00000233170 
               
               
                 6 
                 ENSG00000233382 
                 NKAPP1 
               
               
                 6 
                 ENSG00000233730 
               
               
                 6 
                 ENSG00000233936 
               
               
                 6 
                 ENSG00000234465 
                 PINLYP 
               
               
                 6 
                 ENSG00000234478 
               
               
                 6 
                 ENSG00000234684 
                 SDCBP2-AS1 
               
               
                 6 
                 ENSG00000234911 
                 TEX21P 
               
               
                 6 
                 ENSG00000235106 
                 LINC00094 
               
               
                 6 
                 ENSG00000235142 
               
               
                 6 
                 ENSG00000235162 
                 C12orf75 
               
               
                 6 
                 ENSG00000235453 
                 TOPORS-AS1 
               
               
                 6 
                 ENSG00000235527 
               
               
                 6 
                 ENSG00000236914 
               
               
                 6 
                 ENSG00000237188 
               
               
                 6 
                 ENSG00000239467 
               
               
                 6 
                 ENSG00000240137 
               
               
                 6 
                 ENSG00000240204 
                 SMKR1 
               
               
                 6 
                 ENSG00000240875 
                 LINC00886 
               
               
                 6 
                 ENSG00000241935 
                 HOGA1 
               
               
                 6 
                 ENSG00000241990 
               
               
                 6 
                 ENSG00000242808 
                 SOX2-OT 
               
               
                 6 
                 ENSG00000242852 
                 ZNF709 
               
               
                 6 
                 ENSG00000243069 
                 ARHGEF26- 
               
               
                   
                   
                 AS1 
               
               
                 6 
                 ENSG00000243627 
               
               
                 6 
                 ENSG00000243660 
                 ZNF487 
               
               
                 6 
                 ENSG00000243667 
                 WDR92 
               
               
                 6 
                 ENSG00000243701 
                 LINC00883 
               
               
                 6 
                 ENSG00000243710 
                 WDR65 
               
               
                 6 
                 ENSG00000243836 
                 WDR86-AS1 
               
               
                 6 
                 ENSG00000243910 
                 TUBA4B 
               
               
                 6 
                 ENSG00000244968 
                 LIFR-AS1 
               
               
                 6 
                 ENSG00000245025 
               
               
                 6 
                 ENSG00000245248 
                 USP2-AS1 
               
               
                 6 
                 ENSG00000245317 
               
               
                 6 
                 ENSG00000245573 
                 BDNF-AS 
               
               
                 6 
                 ENSG00000245694 
                 CRNDE 
               
               
                 6 
                 ENSG00000245750 
               
               
                 6 
                 ENSG00000246016 
               
               
                 6 
                 ENSG00000246250 
               
               
                 6 
                 ENSG00000246308 
               
               
                 6 
                 ENSG00000246705 
                 H2AFJ 
               
               
                 6 
                 ENSG00000247081 
               
               
                 6 
                 ENSG00000247271 
                 ZBED5-AS1 
               
               
                 6 
                 ENSG00000247311 
               
               
                 6 
                 ENSG00000247363 
               
               
                 6 
                 ENSG00000247746 
                 USP51 
               
               
                 6 
                 ENSG00000247796 
               
               
                 6 
                 ENSG00000247853 
               
               
                 6 
                 ENSG00000248008 
                 DYNLL1-AS1 
               
               
                 6 
                 ENSG00000248508 
                 SRP14-AS1 
               
               
                 6 
                 ENSG00000248712 
                 CCDC153 
               
               
                 6 
                 ENSG00000248801 
               
               
                 6 
                 ENSG00000248905 
                 FMN1 
               
               
                 6 
                 ENSG00000248932 
               
               
                 6 
                 ENSG00000249042 
               
               
                 6 
                 ENSG00000249241 
               
               
                 6 
                 ENSG00000249348 
                 UGDH-AS1 
               
               
                 6 
                 ENSG00000249481 
                 SPATS1 
               
               
                 6 
                 ENSG00000249610 
               
               
                 6 
                 ENSG00000249621 
               
               
                 6 
                 ENSG00000250056 
                 LINC01018 
               
               
                 6 
                 ENSG00000250462 
                 LRRC37BP1 
               
               
                 6 
                 ENSG00000250510 
                 GPR162 
               
               
                 6 
                 ENSG00000250790 
               
               
                 6 
                 ENSG00000251307 
               
               
                 6 
                 ENSG00000251503 
                 APITD1-CORT 
               
               
                 6 
                 ENSG00000251602 
               
               
                 6 
                 ENSG00000251669 
                 FAM86EP 
               
               
                 6 
                 ENSG00000253302 
                 STAU2-AS1 
               
               
                 6 
                 ENSG00000253320 
               
               
                 6 
                 ENSG00000253379 
               
               
                 6 
                 ENSG00000253719 
                 ATXN7L3B 
               
               
                 6 
                 ENSG00000253948 
               
               
                 6 
                 ENSG00000254024 
               
               
                 6 
                 ENSG00000254389 
                 RHPN1-AS1 
               
               
                 6 
                 ENSG00000254473 
               
               
                 6 
                 ENSG00000254608 
               
               
                 6 
                 ENSG00000254837 
               
               
                 6 
                 ENSG00000255036 
               
               
                 6 
                 ENSG00000255277 
                 ABCC6P2 
               
               
                 6 
                 ENSG00000256061 
                 DYX1C1 
               
               
                 6 
                 ENSG00000256073 
                 C21orf119 
               
               
                 6 
                 ENSG00000257057 
                 LINC01171 
               
               
                 6 
                 ENSG00000257084 
               
               
                 6 
                 ENSG00000257108 
                 NHLRC4 
               
               
                 6 
                 ENSG00000257542 
                 OR7E47P 
               
               
                 6 
                 ENSG00000257698 
               
               
                 6 
                 ENSG00000258334 
               
               
                 6 
                 ENSG00000258539 
               
               
                 6 
                 ENSG00000258701 
                 LINC00638 
               
               
                 6 
                 ENSG00000258940 
               
               
                 6 
                 ENSG00000259087 
               
               
                 6 
                 ENSG00000259225 
               
               
                 6 
                 ENSG00000259251 
               
               
                 6 
                 ENSG00000259264 
               
               
                 6 
                 ENSG00000259319 
               
               
                 6 
                 ENSG00000259426 
               
               
                 6 
                 ENSG00000259577 
               
               
                 6 
                 ENSG00000259802 
               
               
                 6 
                 ENSG00000259901 
               
               
                 6 
                 ENSG00000260018 
               
               
                 6 
                 ENSG00000260057 
               
               
                 6 
                 ENSG00000260136 
               
               
                 6 
                 ENSG00000260328 
               
               
                 6 
                 ENSG00000260372 
                 AQP4-AS1 
               
               
                 6 
                 ENSG00000260517 
               
               
                 6 
                 ENSG00000260526 
               
               
                 6 
                 ENSG00000260604 
               
               
                 6 
                 ENSG00000260643 
               
               
                 6 
                 ENSG00000260908 
               
               
                 6 
                 ENSG00000260951 
               
               
                 6 
                 ENSG00000261188 
               
               
                 6 
                 ENSG00000261572 
               
               
                 6 
                 ENSG00000261652 
                 C15orf65 
               
               
                 6 
                 ENSG00000261759 
               
               
                 6 
                 ENSG00000261777 
               
               
                 6 
                 ENSG00000263011 
               
               
                 6 
                 ENSG00000263812 
                 LINC00908 
               
               
                 6 
                 ENSG00000265666 
               
               
                 6 
                 ENSG00000265688 
                 MAFG-AS1 
               
               
                 6 
                 ENSG00000265752 
               
               
                 6 
                 ENSG00000266947 
               
               
                 6 
                 ENSG00000267100 
                 ILF3-AS1 
               
               
                 6 
                 ENSG00000267106 
                 C19orf82 
               
               
                 6 
                 ENSG00000267128 
                 RNF157-AS1 
               
               
                 6 
                 ENSG00000267348 
               
               
                 6 
                 ENSG00000267390 
               
               
                 6 
                 ENSG00000267439 
               
               
                 6 
                 ENSG00000267848 
               
               
                 6 
                 ENSG00000268061 
                 NAPA-AS1 
               
               
                 6 
                 ENSG00000268175 
               
               
                 6 
                 ENSG00000268565 
               
               
                 6 
                 ENSG00000269916 
               
               
                 6 
                 ENSG00000270021 
               
               
                 6 
                 ENSG00000270362 
                 HMGN3-AS1 
               
               
                 6 
                 ENSG00000270504 
               
               
                 6 
                 ENSG00000270820 
               
               
                 6 
                 ENSG00000271133 
               
               
                 6 
                 ENSG00000271853 
               
               
                 6 
                 ENSG00000272079 
               
               
                 6 
                 ENSG00000272086 
               
               
                 6 
                 ENSG00000272106 
               
               
                 6 
                 ENSG00000272143 
                 FGF14-AS2 
               
               
                 6 
                 ENSG00000272168 
                 CASC15 
               
               
                 6 
                 ENSG00000272288 
               
               
                 6 
                 ENSG00000272323 
               
               
                 6 
                 ENSG00000272442 
               
               
                 6 
                 ENSG00000272502 
               
               
                 6 
                 ENSG00000272514 
               
               
                 6 
                 ENSG00000272831 
               
               
                 6 
                 ENSG00000272902 
               
               
                 6 
                 ENSG00000273061 
               
               
                 6 
                 ENSG00000273071 
               
               
                 7 
                 ENSG00000008988 
                 RPS20 
               
               
                 7 
                 ENSG00000063046 
                 EIF4B 
               
               
                 7 
                 ENSG00000063177 
                 RPL18 
               
               
                 7 
                 ENSG00000071082 
                 RPL31 
               
               
                 7 
                 ENSG00000083845 
                 RPS5 
               
               
                 7 
                 ENSG00000084090 
                 STARD7 
               
               
                 7 
                 ENSG00000089009 
                 RPL6 
               
               
                 7 
                 ENSG00000089157 
                 RPLP0 
               
               
                 7 
                 ENSG00000089289 
                 IGBP1 
               
               
                 7 
                 ENSG00000100129 
                 EIF3L 
               
               
                 7 
                 ENSG00000100316 
                 RPL3 
               
               
                 7 
                 ENSG00000100353 
                 EIF3D 
               
               
                 7 
                 ENSG00000100814 
                 CCNB1IP1 
               
               
                 7 
                 ENSG00000104408 
                 EIF3E 
               
               
                 7 
                 ENSG00000104529 
                 EEF1D 
               
               
                 7 
                 ENSG00000105193 
                 RPS16 
               
               
                 7 
                 ENSG00000105202 
                 FBL 
               
               
                 7 
                 ENSG00000105372 
                 RPS19 
               
               
                 7 
                 ENSG00000105373 
                 GLTSCR2 
               
               
                 7 
                 ENSG00000105640 
                 RPL18A 
               
               
                 7 
                 ENSG00000107625 
                 DDX50 
               
               
                 7 
                 ENSG00000108107 
                 RPL28 
               
               
                 7 
                 ENSG00000108298 
                 RPL19 
               
               
                 7 
                 ENSG00000108604 
                 SMARCD2 
               
               
                 7 
                 ENSG00000109475 
                 RPL34 
               
               
                 7 
                 ENSG00000110700 
                 RPS13 
               
               
                 7 
                 ENSG00000111678 
                 C12orf57 
               
               
                 7 
                 ENSG00000112306 
                 RPS12 
               
               
                 7 
                 ENSG00000114391 
                 RPL24 
               
               
                 7 
                 ENSG00000114942 
                 EEF1B2 
               
               
                 7 
                 ENSG00000115268 
                 RPS15 
               
               
                 7 
                 ENSG00000116251 
                 RPL22 
               
               
                 7 
                 ENSG00000117543 
                 DPH5 
               
               
                 7 
                 ENSG00000118181 
                 RPS25 
               
               
                 7 
                 ENSG00000118816 
                 CCNI 
               
               
                 7 
                 ENSG00000122026 
                 RPL21 
               
               
                 7 
                 ENSG00000122406 
                 RPL5 
               
               
                 7 
                 ENSG00000124614 
                 RPS10 
               
               
                 7 
                 ENSG00000125691 
                 RPL23 
               
               
                 7 
                 ENSG00000125743 
                 SNRPD2 
               
               
                 7 
                 ENSG00000126088 
                 UROD 
               
               
                 7 
                 ENSG00000129158 
                 SERGEF 
               
               
                 7 
                 ENSG00000130159 
                 ECSIT 
               
               
                 7 
                 ENSG00000130255 
                 RPL36 
               
               
                 7 
                 ENSG00000130312 
                 MRPL34 
               
               
                 7 
                 ENSG00000131143 
                 COX4I1 
               
               
                 7 
                 ENSG00000131469 
                 RPL27 
               
               
                 7 
                 ENSG00000133112 
                 TPT1 
               
               
                 7 
                 ENSG00000134419 
                 RPS15A 
               
               
                 7 
                 ENSG00000135390 
                 ATP5G2 
               
               
                 7 
                 ENSG00000136104 
                 RNASEH2B 
               
               
                 7 
                 ENSG00000136710 
                 CCDC115 
               
               
                 7 
                 ENSG00000136942 
                 RPL35 
               
               
                 7 
                 ENSG00000137054 
                 POLR1E 
               
               
                 7 
                 ENSG00000137154 
                 RPS6 
               
               
                 7 
                 ENSG00000137818 
                 RPLP1 
               
               
                 7 
                 ENSG00000137970 
                 RPL7P9 
               
               
                 7 
                 ENSG00000138326 
                 RPS24 
               
               
                 7 
                 ENSG00000139239 
                 RPL14P1 
               
               
                 7 
                 ENSG00000140905 
                 GCSH 
               
               
                 7 
                 ENSG00000140988 
                 RPS2 
               
               
                 7 
                 ENSG00000142534 
                 RPS11 
               
               
                 7 
                 ENSG00000142541 
                 RPL13A 
               
               
                 7 
                 ENSG00000142676 
                 RPL11 
               
               
                 7 
                 ENSG00000142937 
                 RPS8 
               
               
                 7 
                 ENSG00000143947 
                 RPS27A 
               
               
                 7 
                 ENSG00000144713 
                 RPL32 
               
               
                 7 
                 ENSG00000144741 
                 SLC25A26 
               
               
                 7 
                 ENSG00000145425 
                 RPS3A 
               
               
                 7 
                 ENSG00000145592 
                 RPL37 
               
               
                 7 
                 ENSG00000145741 
                 BTF3 
               
               
                 7 
                 ENSG00000147403 
                 RPL10 
               
               
                 7 
                 ENSG00000147604 
                 RPL7 
               
               
                 7 
                 ENSG00000147654 
                 EBAG9 
               
               
                 7 
                 ENSG00000147677 
                 EIF3H 
               
               
                 7 
                 ENSG00000148303 
                 RPL7A 
               
               
                 7 
                 ENSG00000149273 
                 RPS3 
               
               
                 7 
                 ENSG00000149806 
                 FAU 
               
               
                 7 
                 ENSG00000151353 
                 TMEM18 
               
               
                 7 
                 ENSG00000156482 
                 RPL30 
               
               
                 7 
                 ENSG00000156508 
                 EEF1A1 
               
               
                 7 
                 ENSG00000156853 
                 ZNF689 
               
               
                 7 
                 ENSG00000161016 
                 RPL8 
               
               
                 7 
                 ENSG00000161970 
                 RPL26 
               
               
                 7 
                 ENSG00000162244 
                 RPL29 
               
               
                 7 
                 ENSG00000163344 
                 PMVK 
               
               
                 7 
                 ENSG00000163682 
                 RPL9 
               
               
                 7 
                 ENSG00000164587 
                 RPS14 
               
               
                 7 
                 ENSG00000166441 
                 RPL27A 
               
               
                 7 
                 ENSG00000166902 
                 MRPL16 
               
               
                 7 
                 ENSG00000167526 
                 RPL13 
               
               
                 7 
                 ENSG00000168028 
                 RPSA 
               
               
                 7 
                 ENSG00000169100 
                 SLC25A6 
               
               
                 7 
                 ENSG00000169714 
                 CNBP 
               
               
                 7 
                 ENSG00000170889 
                 RPS9 
               
               
                 7 
                 ENSG00000171858 
                 RPS21 
               
               
                 7 
                 ENSG00000171863 
                 RPS7 
               
               
                 7 
                 ENSG00000172809 
                 RPL38 
               
               
                 7 
                 ENSG00000173726 
                 TOMM20 
               
               
                 7 
                 ENSG00000174444 
                 RPL4 
               
               
                 7 
                 ENSG00000174547 
                 MRPL11 
               
               
                 7 
                 ENSG00000174748 
                 RPL15 
               
               
                 7 
                 ENSG00000175061 
                 FAM211A- 
               
               
                   
                   
                 AS1 
               
               
                 7 
                 ENSG00000175390 
                 EIF3F 
               
               
                 7 
                 ENSG00000177410 
                 ZFAS1 
               
               
                 7 
                 ENSG00000177600 
                 RPLP2 
               
               
                 7 
                 ENSG00000177954 
                 RPS27 
               
               
                 7 
                 ENSG00000178464 
               
               
                 7 
                 ENSG00000182774 
                 RPS17L 
               
               
                 7 
                 ENSG00000182899 
                 RPL35A 
               
               
                 7 
                 ENSG00000183405 
                 RPS7P1 
               
               
                 7 
                 ENSG00000184779 
                 RPS17 
               
               
                 7 
                 ENSG00000185641 
               
               
                 7 
                 ENSG00000186468 
                 RPS23 
               
               
                 7 
                 ENSG00000188243 
                 COMMD6 
               
               
                 7 
                 ENSG00000188846 
                 RPL14 
               
               
                 7 
                 ENSG00000189343 
                 RPS2P46 
               
               
                 7 
                 ENSG00000196205 
                 EEF1A1P5 
               
               
                 7 
                 ENSG00000196531 
                 NACA 
               
               
                 7 
                 ENSG00000196683 
                 TOMM7 
               
               
                 7 
                 ENSG00000197756 
                 RPL37A 
               
               
                 7 
                 ENSG00000197958 
                 RPL12 
               
               
                 7 
                 ENSG00000198034 
                 RPS4X 
               
               
                 7 
                 ENSG00000198242 
                 RPL23A 
               
               
                 7 
                 ENSG00000198546 
                 ZNF511 
               
               
                 7 
                 ENSG00000198755 
                 RPL10A 
               
               
                 7 
                 ENSG00000198918 
                 RPL39 
               
               
                 7 
                 ENSG00000204196 
               
               
                 7 
                 ENSG00000204387 
                 C6orf48 
               
               
                 7 
                 ENSG00000204628 
                 GNB2L1 
               
               
                 7 
                 ENSG00000205246 
                 RPSAP58 
               
               
                 7 
                 ENSG00000212802 
                 RPL15P3 
               
               
                 7 
                 ENSG00000213178 
               
               
                 7 
                 ENSG00000213442 
                 RPL18AP3 
               
               
                 7 
                 ENSG00000213553 
                 RPLP0P6 
               
               
                 7 
                 ENSG00000213741 
                 RPS29 
               
               
                 7 
                 ENSG00000213860 
                 RPL21P75 
               
               
                 7 
                 ENSG00000214046 
                 SMIM7 
               
               
                 7 
                 ENSG00000214113 
                 LYRM4 
               
               
                 7 
                 ENSG00000214389 
                 RPS3AP26 
               
               
                 7 
                 ENSG00000214485 
                 RPL7P1 
               
               
                 7 
                 ENSG00000214784 
               
               
                 7 
                 ENSG00000215021 
                 PHB2 
               
               
                 7 
                 ENSG00000218426 
               
               
                 7 
                 ENSG00000220749 
                 RPL21P28 
               
               
                 7 
                 ENSG00000220842 
               
               
                 7 
                 ENSG00000221983 
                 UBA52 
               
               
                 7 
                 ENSG00000226084 
               
               
                 7 
                 ENSG00000226221 
               
               
                 7 
                 ENSG00000227063 
                 RPL41P1 
               
               
                 7 
                 ENSG00000227081 
               
               
                 7 
                 ENSG00000229117 
                 RPL41 
               
               
                 7 
                 ENSG00000229638 
                 RPL4P4 
               
               
                 7 
                 ENSG00000230629 
                 RPS23P8 
               
               
                 7 
                 ENSG00000231500 
                 RPS18 
               
               
                 7 
                 ENSG00000232472 
                 EEF1B2P3 
               
               
                 7 
                 ENSG00000232573 
                 RPL3P4 
               
               
                 7 
                 ENSG00000233476 
                 EEF1A1P6 
               
               
                 7 
                 ENSG00000233762 
               
               
                 7 
                 ENSG00000233913 
               
               
                 7 
                 ENSG00000233927 
                 RPS28 
               
               
                 7 
                 ENSG00000234741 
                 GAS5 
               
               
                 7 
                 ENSG00000234797 
                 RPS3AP6 
               
               
                 7 
                 ENSG00000234851 
               
               
                 7 
                 ENSG00000235065 
                 RPL24P2 
               
               
                 7 
                 ENSG00000235552 
                 RPL6P27 
               
               
                 7 
                 ENSG00000236552 
                 RPL13AP5 
               
               
                 7 
                 ENSG00000240087 
               
               
                 7 
                 ENSG00000240342 
                 RPS2P5 
               
               
                 7 
                 ENSG00000241343 
                 RPL36A 
               
               
                 7 
                 ENSG00000242071 
                 RPL7AP6 
               
               
                 7 
                 ENSG00000242299 
               
               
                 7 
                 ENSG00000243199 
               
               
                 7 
                 ENSG00000244313 
               
               
                 7 
                 ENSG00000244398 
               
               
                 7 
                 ENSG00000244716 
               
               
                 7 
                 ENSG00000245910 
                 SNHG6 
               
               
                 7 
                 ENSG00000254772 
                 EEF1G 
               
               
                 7 
                 ENSG00000265681 
                 RPL17 
               
               
                 7 
                 ENSG00000269893 
                 SNHG8 
               
               
                 8 
                 ENSG00000000938 
                 FGR 
               
               
                 8 
                 ENSG00000005844 
                 ITGAL 
               
               
                 8 
                 ENSG00000006074 
                 CCL18 
               
               
                 8 
                 ENSG00000006075 
                 CCL3 
               
               
                 8 
                 ENSG00000008516 
                 MMP25 
               
               
                 8 
                 ENSG00000009790 
                 TRAF3IP3 
               
               
                 8 
                 ENSG00000010295 
                 IFFO1 
               
               
                 8 
                 ENSG00000010671 
                 BTK 
               
               
                 8 
                 ENSG00000010810 
                 FYN 
               
               
                 8 
                 ENSG00000011600 
                 TYROBP 
               
               
                 8 
                 ENSG00000012779 
                 ALOX5 
               
               
                 8 
                 ENSG00000013725 
                 CD6 
               
               
                 8 
                 ENSG00000015285 
                 WAS 
               
               
                 8 
                 ENSG00000018280 
                 SLC11A1 
               
               
                 8 
                 ENSG00000019169 
                 MARCO 
               
               
                 8 
                 ENSG00000023902 
                 PLEKHO1 
               
               
                 8 
                 ENSG00000026297 
                 RNASET2 
               
               
                 8 
                 ENSG00000027869 
                 SH2D2A 
               
               
                 8 
                 ENSG00000028137 
                 TNFRSF1B 
               
               
                 8 
                 ENSG00000033327 
                 GAB2 
               
               
                 8 
                 ENSG00000038945 
                 MSR1 
               
               
                 8 
                 ENSG00000043462 
                 LCP2 
               
               
                 8 
                 ENSG00000048740 
                 CELF2 
               
               
                 8 
                 ENSG00000054967 
                 RELT 
               
               
                 8 
                 ENSG00000057657 
                 PRDM1 
               
               
                 8 
                 ENSG00000059377 
                 TBXAS1 
               
               
                 8 
                 ENSG00000059728 
                 MXD1 
               
               
                 8 
                 ENSG00000059804 
                 SLC2A3 
               
               
                 8 
                 ENSG00000062282 
                 DGAT2 
               
               
                 8 
                 ENSG00000064201 
                 TSPAN32 
               
               
                 8 
                 ENSG00000065413 
                 ANKRD44 
               
               
                 8 
                 ENSG00000065675 
                 PRKCQ 
               
               
                 8 
                 ENSG00000066294 
                 CD84 
               
               
                 8 
                 ENSG00000066336 
                 SPI1 
               
               
                 8 
                 ENSG00000068831 
                 RASGRP2 
               
               
                 8 
                 ENSG00000069424 
                 KCNAB2 
               
               
                 8 
                 ENSG00000072401 
                 UBE2D1 
               
               
                 8 
                 ENSG00000072694 
                 FCGR2B 
               
               
                 8 
                 ENSG00000072786 
                 STK10 
               
               
                 8 
                 ENSG00000072818 
                 ACAP1 
               
               
                 8 
                 ENSG00000073921 
                 PICALM 
               
               
                 8 
                 ENSG00000074706 
                 IPCEF1 
               
               
                 8 
                 ENSG00000074966 
                 TXK 
               
               
                 8 
                 ENSG00000075624 
                 ACTB 
               
               
                 8 
                 ENSG00000075884 
                 ARHGAP15 
               
               
                 8 
                 ENSG00000076641 
                 PAG1 
               
               
                 8 
                 ENSG00000076662 
                 ICAM3 
               
               
                 8 
                 ENSG00000076928 
                 ARHGEF1 
               
               
                 8 
                 ENSG00000077420 
                 APBB1IP 
               
               
                 8 
                 ENSG00000077984 
                 CST7 
               
               
                 8 
                 ENSG00000078589 
                 P2RY10 
               
               
                 8 
                 ENSG00000079263 
                 SP140 
               
               
                 8 
                 ENSG00000081059 
                 TCF7 
               
               
                 8 
                 ENSG00000081087 
                 OSTM1 
               
               
                 8 
                 ENSG00000081237 
                 PTPRC 
               
               
                 8 
                 ENSG00000081320 
                 STK17B 
               
               
                 8 
                 ENSG00000082074 
                 FYB 
               
               
                 8 
                 ENSG00000085265 
                 FCN1 
               
               
                 8 
                 ENSG00000085514 
                 PILRA 
               
               
                 8 
                 ENSG00000086300 
                 SNX10 
               
               
                 8 
                 ENSG00000086730 
                 LAT2 
               
               
                 8 
                 ENSG00000087266 
                 SH3BP2 
               
               
                 8 
                 ENSG00000088827 
                 SIGLEC1 
               
               
                 8 
                 ENSG00000089327 
                 FXYD5 
               
               
                 8 
                 ENSG00000089639 
                 GMIP 
               
               
                 8 
                 ENSG00000089820 
                 ARHGAP4 
               
               
                 8 
                 ENSG00000090339 
                 ICAM1 
               
               
                 8 
                 ENSG00000090674 
                 MCOLN1 
               
               
                 8 
                 ENSG00000091106 
                 NLRC4 
               
               
                 8 
                 ENSG00000092929 
                 UNC13D 
               
               
                 8 
                 ENSG00000095303 
                 PTGS1 
               
               
                 8 
                 ENSG00000095370 
                 SH2D3C 
               
               
                 8 
                 ENSG00000096996 
                 IL12RB1 
               
               
                 8 
                 ENSG00000099308 
                 MAST3 
               
               
                 8 
                 ENSG00000099985 
                 OSM 
               
               
                 8 
                 ENSG00000100055 
                 CYTH4 
               
               
                 8 
                 ENSG00000100060 
                 MFNG 
               
               
                 8 
                 ENSG00000100351 
                 GRAP2 
               
               
                 8 
                 ENSG00000100365 
                 NCF4 
               
               
                 8 
                 ENSG00000100368 
                 CSF2RB 
               
               
                 8 
                 ENSG00000100385 
                 IL2RB 
               
               
                 8 
                 ENSG00000100599 
                 RIN3 
               
               
                 8 
                 ENSG00000100985 
                 MMP9 
               
               
                 8 
                 ENSG00000101109 
                 STK4 
               
               
                 8 
                 ENSG00000101265 
                 RASSF2 
               
               
                 8 
                 ENSG00000101307 
                 SIRPB1 
               
               
                 8 
                 ENSG00000101336 
                 HCK 
               
               
                 8 
                 ENSG00000101916 
                 TLR8 
               
               
                 8 
                 ENSG00000102032 
                 RENBP 
               
               
                 8 
                 ENSG00000102218 
                 RP2 
               
               
                 8 
                 ENSG00000102445 
                 KIAA0226L 
               
               
                 8 
                 ENSG00000102524 
                 TNFSF13B 
               
               
                 8 
                 ENSG00000102575 
                 ACP5 
               
               
                 8 
                 ENSG00000102879 
                 CORO1A 
               
               
                 8 
                 ENSG00000103005 
                 USB1 
               
               
                 8 
                 ENSG00000103187 
                 COTL1 
               
               
                 8 
                 ENSG00000103313 
                 MEFV 
               
               
                 8 
                 ENSG00000103522 
                 IL21R 
               
               
                 8 
                 ENSG00000103569 
                 AQP9 
               
               
                 8 
                 ENSG00000104814 
                 MAP4K1 
               
               
                 8 
                 ENSG00000104894 
                 CD37 
               
               
                 8 
                 ENSG00000104972 
                 LILRB1 
               
               
                 8 
                 ENSG00000104998 
                 IL27RA 
               
               
                 8 
                 ENSG00000105122 
                 RASAL3 
               
               
                 8 
                 ENSG00000105329 
                 TGFB1 
               
               
                 8 
                 ENSG00000105339 
                 DENND3 
               
               
                 8 
                 ENSG00000105483 
                 CARD8 
               
               
                 8 
                 ENSG00000105639 
                 JAK3 
               
               
                 8 
                 ENSG00000105835 
                 NAMPT 
               
               
                 8 
                 ENSG00000105851 
                 PIK3CG 
               
               
                 8 
                 ENSG00000105967 
                 TFEC 
               
               
                 8 
                 ENSG00000106066 
                 CPVL 
               
               
                 8 
                 ENSG00000106348 
                 IMPDH1 
               
               
                 8 
                 ENSG00000107099 
                 DOCK8 
               
               
                 8 
                 ENSG00000107485 
                 GATA3 
               
               
                 8 
                 ENSG00000107551 
                 RASSF4 
               
               
                 8 
                 ENSG00000108405 
                 P2RX1 
               
               
                 8 
                 ENSG00000108932 
                 SLC16A6 
               
               
                 8 
                 ENSG00000108960 
                 MMD 
               
               
                 8 
                 ENSG00000109743 
                 BST1 
               
               
                 8 
                 ENSG00000110031 
                 LPXN 
               
               
                 8 
                 ENSG00000110047 
                 EHD1 
               
               
                 8 
                 ENSG00000110077 
                 MS4A6A 
               
               
                 8 
                 ENSG00000110079 
                 MS4A4A 
               
               
                 8 
                 ENSG00000110324 
                 IL10RA 
               
               
                 8 
                 ENSG00000110395 
                 CBL 
               
               
                 8 
                 ENSG00000110446 
                 SLC15A3 
               
               
                 8 
                 ENSG00000110448 
                 CD5 
               
               
                 8 
                 ENSG00000110848 
                 CD69 
               
               
                 8 
                 ENSG00000110876 
                 SELPLG 
               
               
                 8 
                 ENSG00000110934 
                 BIN2 
               
               
                 8 
                 ENSG00000111252 
                 SH2B3 
               
               
                 8 
                 ENSG00000111348 
                 ARHGDIB 
               
               
                 8 
                 ENSG00000111679 
                 PTPN6 
               
               
                 8 
                 ENSG00000111729 
                 CLEC4A 
               
               
                 8 
                 ENSG00000112096 
                 SOD2 
               
               
                 8 
                 ENSG00000112137 
                 PHACTR1 
               
               
                 8 
                 ENSG00000112149 
                 CD83 
               
               
                 8 
                 ENSG00000112195 
                 TREML2 
               
               
                 8 
                 ENSG00000112303 
                 VNN2 
               
               
                 8 
                 ENSG00000112531 
                 QKI 
               
               
                 8 
                 ENSG00000112799 
                 LY86 
               
               
                 8 
                 ENSG00000113263 
                 ITK 
               
               
                 8 
                 ENSG00000113273 
                 ARSB 
               
               
                 8 
                 ENSG00000114013 
                 CD86 
               
               
                 8 
                 ENSG00000114450 
                 GNB4 
               
               
                 8 
                 ENSG00000114626 
                 ABTB1 
               
               
                 8 
                 ENSG00000114737 
                 CISH 
               
               
                 8 
                 ENSG00000115085 
                 ZAP70 
               
               
                 8 
                 ENSG00000115165 
                 CYTIP 
               
               
                 8 
                 ENSG00000115232 
                 ITGA4 
               
               
                 8 
                 ENSG00000115271 
                 GCA 
               
               
                 8 
                 ENSG00000115318 
                 LOXL3 
               
               
                 8 
                 ENSG00000115325 
                 DOK1 
               
               
                 8 
                 ENSG00000115355 
                 CCDC88A 
               
               
                 8 
                 ENSG00000115604 
                 IL18R1 
               
               
                 8 
                 ENSG00000115607 
                 IL18RAP 
               
               
                 8 
                 ENSG00000115756 
                 HPCAL1 
               
               
                 8 
                 ENSG00000115828 
                 QPCT 
               
               
                 8 
                 ENSG00000115935 
                 WIPF1 
               
               
                 8 
                 ENSG00000115956 
                 PLEK 
               
               
                 8 
                 ENSG00000116017 
                 ARID3A 
               
               
                 8 
                 ENSG00000116337 
                 AMPD2 
               
               
                 8 
                 ENSG00000116701 
                 NCF2 
               
               
                 8 
                 ENSG00000116741 
                 RGS2 
               
               
                 8 
                 ENSG00000116824 
                 CD2 
               
               
                 8 
                 ENSG00000116852 
                 KIF21B 
               
               
                 8 
                 ENSG00000117009 
                 KMO 
               
               
                 8 
                 ENSG00000117090 
                 SLAMF1 
               
               
                 8 
                 ENSG00000117091 
                 CD48 
               
               
                 8 
                 ENSG00000117115 
                 PADI2 
               
               
                 8 
                 ENSG00000117281 
                 CD160 
               
               
                 8 
                 ENSG00000118263 
                 KLF7 
               
               
                 8 
                 ENSG00000118508 
                 RAB32 
               
               
                 8 
                 ENSG00000119321 
                 FKBP15 
               
               
                 8 
                 ENSG00000119535 
                 CSF3R 
               
               
                 8 
                 ENSG00000119686 
                 FLVCR2 
               
               
                 8 
                 ENSG00000120063 
                 GNA13 
               
               
                 8 
                 ENSG00000120709 
                 FAM53C 
               
               
                 8 
                 ENSG00000120899 
                 PTK2B 
               
               
                 8 
                 ENSG00000121060 
                 TRIM25 
               
               
                 8 
                 ENSG00000121210 
                 KIAA0922 
               
               
                 8 
                 ENSG00000121281 
                 ADCY7 
               
               
                 8 
                 ENSG00000121797 
                 CCRL2 
               
               
                 8 
                 ENSG00000121807 
                 CCR2 
               
               
                 8 
                 ENSG00000121966 
                 CXCR4 
               
               
                 8 
                 ENSG00000122122 
                 SASH3 
               
               
                 8 
                 ENSG00000122188 
                 LAX1 
               
               
                 8 
                 ENSG00000122224 
                 LY9 
               
               
                 8 
                 ENSG00000122862 
                 SRGN 
               
               
                 8 
                 ENSG00000122986 
                 HVCN1 
               
               
                 8 
                 ENSG00000123329 
                 ARHGAP9 
               
               
                 8 
                 ENSG00000123338 
                 NCKAP1L 
               
               
                 8 
                 ENSG00000123689 
                 G0S2 
               
               
                 8 
                 ENSG00000124126 
                 PREX1 
               
               
                 8 
                 ENSG00000124203 
                 ZNF831 
               
               
                 8 
                 ENSG00000124334 
                 IL9R 
               
               
                 8 
                 ENSG00000124357 
                 NAGK 
               
               
                 8 
                 ENSG00000124491 
                 F13A1 
               
               
                 8 
                 ENSG00000124731 
                 TREM1 
               
               
                 8 
                 ENSG00000125354 
                 6-Sep 
               
               
                 8 
                 ENSG00000125538 
                 IL1B 
               
               
                 8 
                 ENSG00000125637 
                 PSD4 
               
               
                 8 
                 ENSG00000125735 
                 TNFSF14 
               
               
                 8 
                 ENSG00000125910 
                 S1PR4 
               
               
                 8 
                 ENSG00000126246 
                 IGFLR1 
               
               
                 8 
                 ENSG00000126262 
                 FFAR2 
               
               
                 8 
                 ENSG00000126264 
                 HCST 
               
               
                 8 
                 ENSG00000126353 
                 CCR7 
               
               
                 8 
                 ENSG00000126561 
                 STAT5A 
               
               
                 8 
                 ENSG00000126860 
                 EVI2A 
               
               
                 8 
                 ENSG00000126882 
                 FAM78A 
               
               
                 8 
                 ENSG00000127084 
                 FGD3 
               
               
                 8 
                 ENSG00000127152 
                 BCL11B 
               
               
                 8 
                 ENSG00000127507 
                 EMR2 
               
               
                 8 
                 ENSG00000127951 
                 FGL2 
               
               
                 8 
                 ENSG00000128271 
                 ADORA2A 
               
               
                 8 
                 ENSG00000128340 
                 RAC2 
               
               
                 8 
                 ENSG00000128383 
                 APOBEC3A 
               
               
                 8 
                 ENSG00000128815 
                 WDFY4 
               
               
                 8 
                 ENSG00000129071 
                 MBD4 
               
               
                 8 
                 ENSG00000129226 
                 CD68 
               
               
                 8 
                 ENSG00000129277 
                 CCL4 
               
               
                 8 
                 ENSG00000129657 
                 SEC14L1 
               
               
                 8 
                 ENSG00000129675 
                 ARHGEF6 
               
               
                 8 
                 ENSG00000130203 
                 APOE 
               
               
                 8 
                 ENSG00000130208 
                 APOC1 
               
               
                 8 
                 ENSG00000130429 
                 ARPC1B 
               
               
                 8 
                 ENSG00000130475 
                 FCHO1 
               
               
                 8 
                 ENSG00000130592 
                 LSP1 
               
               
                 8 
                 ENSG00000130755 
                 GMFG 
               
               
                 8 
                 ENSG00000130775 
                 THEMIS2 
               
               
                 8 
                 ENSG00000130830 
                 MPP1 
               
               
                 8 
                 ENSG00000131042 
                 LILRB2 
               
               
                 8 
                 ENSG00000131378 
                 RFTN1 
               
               
                 8 
                 ENSG00000131401 
                 NAPSB 
               
               
                 8 
                 ENSG00000131669 
                 NINJ1 
               
               
                 8 
                 ENSG00000131724 
                 IL13RA1 
               
               
                 8 
                 ENSG00000132182 
                 NUP210 
               
               
                 8 
                 ENSG00000132205 
                 EMILIN2 
               
               
                 8 
                 ENSG00000132334 
                 PTPRE 
               
               
                 8 
                 ENSG00000132510 
                 KDM6B 
               
               
                 8 
                 ENSG00000132514 
                 CLEC10A 
               
               
                 8 
                 ENSG00000132965 
                 ALOX5AP 
               
               
                 8 
                 ENSG00000133048 
                 CHI3L1 
               
               
                 8 
                 ENSG00000133246 
                 PRAM1 
               
               
                 8 
                 ENSG00000133574 
                 GIMAP4 
               
               
                 8 
                 ENSG00000133961 
                 NUMB 
               
               
                 8 
                 ENSG00000134242 
                 PTPN22 
               
               
                 8 
                 ENSG00000134516 
                 DOCK2 
               
               
                 8 
                 ENSG00000134668 
                 SPOCD1 
               
               
                 8 
                 ENSG00000134686 
                 PHC2 
               
               
                 8 
                 ENSG00000134698 
                 AGO4 
               
               
                 8 
                 ENSG00000134830 
                 C5AR2 
               
               
                 8 
                 ENSG00000134954 
                 ETS1 
               
               
                 8 
                 ENSG00000135074 
                 ADAM19 
               
               
                 8 
                 ENSG00000135077 
                 HAVCR2 
               
               
                 8 
                 ENSG00000135218 
                 CD36 
               
               
                 8 
                 ENSG00000135426 
                 TESPA1 
               
               
                 8 
                 ENSG00000135439 
                 AGAP2 
               
               
                 8 
                 ENSG00000135604 
                 STX11 
               
               
                 8 
                 ENSG00000135636 
                 DYSF 
               
               
                 8 
                 ENSG00000135838 
                 NPL 
               
               
                 8 
                 ENSG00000135905 
                 DOCK10 
               
               
                 8 
                 ENSG00000136040 
                 PLXNC1 
               
               
                 8 
                 ENSG00000136111 
                 TBC1D4 
               
               
                 8 
                 ENSG00000136167 
                 LCP1 
               
               
                 8 
                 ENSG00000136250 
                 AOAH 
               
               
                 8 
                 ENSG00000136286 
                 MYO1G 
               
               
                 8 
                 ENSG00000136404 
                 TM6SF1 
               
               
                 8 
                 ENSG00000136490 
                 LIMD2 
               
               
                 8 
                 ENSG00000136560 
                 TANK 
               
               
                 8 
                 ENSG00000136867 
                 SLC31A2 
               
               
                 8 
                 ENSG00000136869 
                 TLR4 
               
               
                 8 
                 ENSG00000137076 
                 TLN1 
               
               
                 8 
                 ENSG00000137078 
                 SIT1 
               
               
                 8 
                 ENSG00000137265 
                 IRF4 
               
               
                 8 
                 ENSG00000137462 
                 TLR2 
               
               
                 8 
                 ENSG00000137491 
                 SLCO2B1 
               
               
                 8 
                 ENSG00000137575 
                 SDCBP 
               
               
                 8 
                 ENSG00000137752 
                 CASP1 
               
               
                 8 
                 ENSG00000137841 
                 PLCB2 
               
               
                 8 
                 ENSG00000138378 
                 STAT4 
               
               
                 8 
                 ENSG00000138621 
                 PPCDC 
               
               
                 8 
                 ENSG00000138964 
                 PARVG 
               
               
                 8 
                 ENSG00000139193 
                 CD27 
               
               
                 8 
                 ENSG00000139278 
                 GLIPR1 
               
               
                 8 
                 ENSG00000139370 
                 SLC15A4 
               
               
                 8 
                 ENSG00000139436 
                 GIT2 
               
               
                 8 
                 ENSG00000140030 
                 GPR65 
               
               
                 8 
                 ENSG00000140368 
                 PSTPIP1 
               
               
                 8 
                 ENSG00000140379 
                 BCL2A1 
               
               
                 8 
                 ENSG00000140678 
                 ITGAX 
               
               
                 8 
                 ENSG00000140749 
                 IGSF6 
               
               
                 8 
                 ENSG00000140931 
                 CMTM3 
               
               
                 8 
                 ENSG00000140968 
                 IRF8 
               
               
                 8 
                 ENSG00000141293 
                 SKAP1 
               
               
                 8 
                 ENSG00000141298 
                 SSH2 
               
               
                 8 
                 ENSG00000141480 
                 ARRB2 
               
               
                 8 
                 ENSG00000141506 
                 PIK3R5 
               
               
                 8 
                 ENSG00000141576 
                 RNF157 
               
               
                 8 
                 ENSG00000142185 
                 TRPM2 
               
               
                 8 
                 ENSG00000142227 
                 EMP3 
               
               
                 8 
                 ENSG00000142347 
                 MYO1F 
               
               
                 8 
                 ENSG00000142512 
                 SIGLEC10 
               
               
                 8 
                 ENSG00000143110 
                 C1orf162 
               
               
                 8 
                 ENSG00000143119 
                 CD53 
               
               
                 8 
                 ENSG00000143226 
                 FCGR2A 
               
               
                 8 
                 ENSG00000143382 
                 ADAMTSL4 
               
               
                 8 
                 ENSG00000143546 
                 S100A8 
               
               
                 8 
                 ENSG00000143851 
                 PTPN7 
               
               
                 8 
                 ENSG00000144218 
                 AFF3 
               
               
                 8 
                 ENSG00000144815 
                 NXPE3 
               
               
                 8 
                 ENSG00000145416 
                 1-Mar 
               
               
                 8 
                 ENSG00000145569 
                 FAM105A 
               
               
                 8 
                 ENSG00000145649 
                 GZMA 
               
               
                 8 
                 ENSG00000145819 
                 ARHGAP26 
               
               
                 8 
                 ENSG00000146070 
                 PLA2G7 
               
               
                 8 
                 ENSG00000146094 
                 DOK3 
               
               
                 8 
                 ENSG00000146112 
                 PPP1R18 
               
               
                 8 
                 ENSG00000146192 
                 FGD2 
               
               
                 8 
                 ENSG00000146278 
                 PNRC1 
               
               
                 8 
                 ENSG00000146285 
                 SCML4 
               
               
                 8 
                 ENSG00000146592 
                 CREB5 
               
               
                 8 
                 ENSG00000146859 
                 TMEM140 
               
               
                 8 
                 ENSG00000147010 
                 SH3KBP1 
               
               
                 8 
                 ENSG00000147065 
                 MSN 
               
               
                 8 
                 ENSG00000147168 
                 IL2RG 
               
               
                 8 
                 ENSG00000147251 
                 DOCK11 
               
               
                 8 
                 ENSG00000147416 
                 ATP6V1B2 
               
               
                 8 
                 ENSG00000147443 
                 DOK2 
               
               
                 8 
                 ENSG00000147454 
                 SLC25A37 
               
               
                 8 
                 ENSG00000147459 
                 DOCK5 
               
               
                 8 
                 ENSG00000147872 
                 PLIN2 
               
               
                 8 
                 ENSG00000148572 
                 NRBF2 
               
               
                 8 
                 ENSG00000148908 
                 RGS10 
               
               
                 8 
                 ENSG00000149091 
                 DGKZ 
               
               
                 8 
                 ENSG00000149177 
                 PTPRJ 
               
               
                 8 
                 ENSG00000149781 
                 FERMT3 
               
               
                 8 
                 ENSG00000150337 
                 FCGR1A 
               
               
                 8 
                 ENSG00000150681 
                 RGS18 
               
               
                 8 
                 ENSG00000150867 
                 PIP4K2A 
               
               
                 8 
                 ENSG00000151490 
                 PTPRO 
               
               
                 8 
                 ENSG00000151651 
                 ADAM8 
               
               
                 8 
                 ENSG00000151702 
                 FLI1 
               
               
                 8 
                 ENSG00000151726 
                 ACSL1 
               
               
                 8 
                 ENSG00000151948 
                 GLT1D1 
               
               
                 8 
                 ENSG00000152213 
                 ARL11 
               
               
                 8 
                 ENSG00000152270 
                 PDE3B 
               
               
                 8 
                 ENSG00000152495 
                 CAMK4 
               
               
                 8 
                 ENSG00000153071 
                 DAB2 
               
               
                 8 
                 ENSG00000153179 
                 RASSF3 
               
               
                 8 
                 ENSG00000153283 
                 CD96 
               
               
                 8 
                 ENSG00000153317 
                 ASAP1 
               
               
                 8 
                 ENSG00000153395 
                 LPCAT1 
               
               
                 8 
                 ENSG00000153563 
                 CD8A 
               
               
                 8 
                 ENSG00000154016 
                 GRAP 
               
               
                 8 
                 ENSG00000154451 
                 GBP5 
               
               
                 8 
                 ENSG00000154589 
                 LY96 
               
               
                 8 
                 ENSG00000155307 
                 SAMSN1 
               
               
                 8 
                 ENSG00000155465 
                 SLC7A7 
               
               
                 8 
                 ENSG00000155629 
                 PIK3AP1 
               
               
                 8 
                 ENSG00000155659 
                 VSIG4 
               
               
                 8 
                 ENSG00000155849 
                 ELMO1 
               
               
                 8 
                 ENSG00000155926 
                 SLA 
               
               
                 8 
                 ENSG00000156273 
                 BACH1 
               
               
                 8 
                 ENSG00000157350 
                 ST3GAL2 
               
               
                 8 
                 ENSG00000157551 
                 KCNJ15 
               
               
                 8 
                 ENSG00000158517 
                 NCF1 
               
               
                 8 
                 ENSG00000158714 
                 SLAMF8 
               
               
                 8 
                 ENSG00000158869 
                 FCER1G 
               
               
                 8 
                 ENSG00000159189 
                 C1QC 
               
               
                 8 
                 ENSG00000159322 
                 ADPGK 
               
               
                 8 
                 ENSG00000159618 
                 GPR114 
               
               
                 8 
                 ENSG00000159753 
                 RLTPR 
               
               
                 8 
                 ENSG00000160185 
                 UBASH3A 
               
               
                 8 
                 ENSG00000160219 
                 GAB3 
               
               
                 8 
                 ENSG00000160255 
                 ITGB2 
               
               
                 8 
                 ENSG00000160326 
                 SLC2A6 
               
               
                 8 
                 ENSG00000160593 
                 AMICA1 
               
               
                 8 
                 ENSG00000160654 
                 CD3G 
               
               
                 8 
                 ENSG00000160883 
                 HK3 
               
               
                 8 
                 ENSG00000160999 
                 SH2B2 
               
               
                 8 
                 ENSG00000161570 
                 CCL5 
               
               
                 8 
                 ENSG00000161791 
                 FMNL3 
               
               
                 8 
                 ENSG00000161929 
                 SCIMP 
               
               
                 8 
                 ENSG00000162511 
                 LAPTM5 
               
               
                 8 
                 ENSG00000162676 
                 GFI1 
               
               
                 8 
                 ENSG00000162711 
                 NLRP3 
               
               
                 8 
                 ENSG00000162739 
                 SLAMF6 
               
               
                 8 
                 ENSG00000163154 
                 TNFAIP8L2 
               
               
                 8 
                 ENSG00000163162 
                 RNF149 
               
               
                 8 
                 ENSG00000163219 
                 ARHGAP25 
               
               
                 8 
                 ENSG00000163220 
                 S100A9 
               
               
                 8 
                 ENSG00000163376 
                 KBTBD8 
               
               
                 8 
                 ENSG00000163421 
                 PROK2 
               
               
                 8 
                 ENSG00000163464 
                 CXCR1 
               
               
                 8 
                 ENSG00000163519 
                 TRAT1 
               
               
                 8 
                 ENSG00000163563 
                 MNDA 
               
               
                 8 
                 ENSG00000163564 
                 PYHIN1 
               
               
                 8 
                 ENSG00000163600 
                 ICOS 
               
               
                 8 
                 ENSG00000163823 
                 CCR1 
               
               
                 8 
                 ENSG00000164691 
                 TAGAP 
               
               
                 8 
                 ENSG00000165030 
                 NFIL3 
               
               
                 8 
                 ENSG00000165168 
                 CYBB 
               
               
                 8 
                 ENSG00000165178 
                 NCF1C 
               
               
                 8 
                 ENSG00000166128 
                 RAB8B 
               
               
                 8 
                 ENSG00000166340 
                 TPP1 
               
               
                 8 
                 ENSG00000166501 
                 PRKCB 
               
               
                 8 
                 ENSG00000166523 
                 CLEC4E 
               
               
                 8 
                 ENSG00000166716 
                 ZNF592 
               
               
                 8 
                 ENSG00000166927 
                 MS4A7 
               
               
                 8 
                 ENSG00000167208 
                 SNX20 
               
               
                 8 
                 ENSG00000167261 
                 DPEP2 
               
               
                 8 
                 ENSG00000167286 
                 CD3D 
               
               
                 8 
                 ENSG00000167483 
                 FAM129C 
               
               
                 8 
                 ENSG00000167613 
                 LAIR1 
               
               
                 8 
                 ENSG00000167680 
                 SEMA6B 
               
               
                 8 
                 ENSG00000167851 
                 CD300A 
               
               
                 8 
                 ENSG00000168067 
                 MAP4K2 
               
               
                 8 
                 ENSG00000168071 
                 CCDC88B 
               
               
                 8 
                 ENSG00000168404 
                 MLKL 
               
               
                 8 
                 ENSG00000168421 
                 RHOH 
               
               
                 8 
                 ENSG00000168685 
                 IL7R 
               
               
                 8 
                 ENSG00000168918 
                 INPP5D 
               
               
                 8 
                 ENSG00000169180 
                 XPO6 
               
               
                 8 
                 ENSG00000169220 
                 RGS14 
               
               
                 8 
                 ENSG00000169228 
                 RAB24 
               
               
                 8 
                 ENSG00000169403 
                 PTAFR 
               
               
                 8 
                 ENSG00000169413 
                 RNASE6 
               
               
                 8 
                 ENSG00000169442 
                 CD52 
               
               
                 8 
                 ENSG00000169508 
                 GPR183 
               
               
                 8 
                 ENSG00000169554 
                 ZEB2 
               
               
                 8 
                 ENSG00000169826 
                 CSGALNACT2 
               
               
                 8 
                 ENSG00000169896 
                 ITGAM 
               
               
                 8 
                 ENSG00000170323 
                 FABP4 
               
               
                 8 
                 ENSG00000170458 
                 CD14 
               
               
                 8 
                 ENSG00000170525 
                 PFKFB3 
               
               
                 8 
                 ENSG00000170542 
                 SERPINB9 
               
               
                 8 
                 ENSG00000170909 
                 OSCAR 
               
               
                 8 
                 ENSG00000170956 
                 CEACAM3 
               
               
                 8 
                 ENSG00000171049 
                 FPR2 
               
               
                 8 
                 ENSG00000171051 
                 FPR1 
               
               
                 8 
                 ENSG00000171488 
                 LRRC8C 
               
               
                 8 
                 ENSG00000171608 
                 PIK3CD 
               
               
                 8 
                 ENSG00000171659 
                 GPR34 
               
               
                 8 
                 ENSG00000171700 
                 RGS19 
               
               
                 8 
                 ENSG00000171777 
                 RASGRP4 
               
               
                 8 
                 ENSG00000171860 
                 C3AR1 
               
               
                 8 
                 ENSG00000172081 
                 MOB3A 
               
               
                 8 
                 ENSG00000172116 
                 CD8B 
               
               
                 8 
                 ENSG00000172216 
                 CEBPB 
               
               
                 8 
                 ENSG00000172243 
                 CLEC7A 
               
               
                 8 
                 ENSG00000172322 
                 CLEC12A 
               
               
                 8 
                 ENSG00000172349 
                 IL16 
               
               
                 8 
                 ENSG00000172543 
                 CTSW 
               
               
                 8 
                 ENSG00000172575 
                 RASGRP1 
               
               
                 8 
                 ENSG00000172673 
                 THEMIS 
               
               
                 8 
                 ENSG00000173020 
                 ADRBK1 
               
               
                 8 
                 ENSG00000173110 
                 HSPA6 
               
               
                 8 
                 ENSG00000173200 
                 PARP15 
               
               
                 8 
                 ENSG00000173281 
                 PPP1R3B 
               
               
                 8 
                 ENSG00000173369 
                 C1QB 
               
               
                 8 
                 ENSG00000173372 
                 C1QA 
               
               
                 8 
                 ENSG00000173391 
                 OLR1 
               
               
                 8 
                 ENSG00000173535 
                 TNFRSF10C 
               
               
                 8 
                 ENSG00000173559 
                 NABP1 
               
               
                 8 
                 ENSG00000173638 
                 SLC19A1 
               
               
                 8 
                 ENSG00000173757 
                 STAT5B 
               
               
                 8 
                 ENSG00000173762 
                 CD7 
               
               
                 8 
                 ENSG00000173868 
                 PHOSPHO1 
               
               
                 8 
                 ENSG00000174004 
                 NRROS 
               
               
                 8 
                 ENSG00000174125 
                 TLR1 
               
               
                 8 
                 ENSG00000174579 
                 MSL2 
               
               
                 8 
                 ENSG00000174600 
                 CMKLR1 
               
               
                 8 
                 ENSG00000174718 
                 KIAA1551 
               
               
                 8 
                 ENSG00000175463 
                 TBC1D10C 
               
               
                 8 
                 ENSG00000175489 
                 LRRC25 
               
               
                 8 
                 ENSG00000175857 
                 GAPT 
               
               
                 8 
                 ENSG00000176390 
                 CRLF3 
               
               
                 8 
                 ENSG00000177105 
                 RHOG 
               
               
                 8 
                 ENSG00000177575 
                 CD163 
               
               
                 8 
                 ENSG00000177663 
                 IL17RA 
               
               
                 8 
                 ENSG00000177885 
                 GRB2 
               
               
                 8 
                 ENSG00000178562 
                 CD28 
               
               
                 8 
                 ENSG00000178607 
                 ERN1 
               
               
                 8 
                 ENSG00000179361 
                 ARID3B 
               
               
                 8 
                 ENSG00000180096 
                 1-Sep 
               
               
                 8 
                 ENSG00000180353 
                 HCLS1 
               
               
                 8 
                 ENSG00000180448 
                 HMHA1 
               
               
                 8 
                 ENSG00000180871 
                 CXCR2 
               
               
                 8 
                 ENSG00000180953 
                 ST20 
               
               
                 8 
                 ENSG00000181381 
                 DDX60L 
               
               
                 8 
                 ENSG00000181409 
                 AATK 
               
               
                 8 
                 ENSG00000181631 
                 P2RY13 
               
               
                 8 
                 ENSG00000182022 
                 CHST15 
               
               
                 8 
                 ENSG00000182287 
                 AP1S2 
               
               
                 8 
                 ENSG00000182487 
                 NCF1B 
               
               
                 8 
                 ENSG00000182511 
                 FES 
               
               
                 8 
                 ENSG00000182578 
                 CSF1R 
               
               
                 8 
                 ENSG00000182866 
                 LCK 
               
               
                 8 
                 ENSG00000182885 
                 GPR97 
               
               
                 8 
                 ENSG00000183019 
                 C19orf59 
               
               
                 8 
                 ENSG00000183023 
                 SLC8A1 
               
               
                 8 
                 ENSG00000183484 
                 GPR132 
               
               
                 8 
                 ENSG00000183688 
                 FAM101B 
               
               
                 8 
                 ENSG00000183748 
               
               
                 8 
                 ENSG00000183918 
                 SH2D1A 
               
               
                 8 
                 ENSG00000184014 
                 DENND5A 
               
               
                 8 
                 ENSG00000184060 
                 ADAP2 
               
               
                 8 
                 ENSG00000184371 
                 CSF1 
               
               
                 8 
                 ENSG00000184588 
                 PDE4B 
               
               
                 8 
                 ENSG00000184602 
                 SNN 
               
               
                 8 
                 ENSG00000184730 
                 APOBR 
               
               
                 8 
                 ENSG00000184922 
                 FMNL1 
               
               
                 8 
                 ENSG00000185201 
                 IFITM2 
               
               
                 8 
                 ENSG00000185215 
                 TNFAIP2 
               
               
                 8 
                 ENSG00000185339 
                 TCN2 
               
               
                 8 
                 ENSG00000185477 
                 GPRIN3 
               
               
                 8 
                 ENSG00000185811 
                 IKZF1 
               
               
                 8 
                 ENSG00000185862 
                 EVI2B 
               
               
                 8 
                 ENSG00000185947 
                 ZNF267 
               
               
                 8 
                 ENSG00000186074 
                 CD300LF 
               
               
                 8 
                 ENSG00000186469 
                 GNG2 
               
               
                 8 
                 ENSG00000186517 
                 ARHGAP30 
               
               
                 8 
                 ENSG00000186635 
                 ARAP1 
               
               
                 8 
                 ENSG00000186818 
                 LILRB4 
               
               
                 8 
                 ENSG00000187116 
                 LILRA5 
               
               
                 8 
                 ENSG00000187239 
                 FNBP1 
               
               
                 8 
                 ENSG00000187474 
                 FPR3 
               
               
                 8 
                 ENSG00000187688 
                 TRPV2 
               
               
                 8 
                 ENSG00000187764 
                 SEMA4D 
               
               
                 8 
                 ENSG00000187796 
                 CARD9 
               
               
                 8 
                 ENSG00000187994 
                 RINL 
               
               
                 8 
                 ENSG00000188404 
                 SELL 
               
               
                 8 
                 ENSG00000188820 
                 FAM26F 
               
               
                 8 
                 ENSG00000188895 
                 MSL1 
               
               
                 8 
                 ENSG00000188906 
                 LRRK2 
               
               
                 8 
                 ENSG00000189067 
                 LITAF 
               
               
                 8 
                 ENSG00000196511 
                 TPK1 
               
               
                 8 
                 ENSG00000196549 
                 MME 
               
               
                 8 
                 ENSG00000196663 
                 TECPR2 
               
               
                 8 
                 ENSG00000196843 
                 ARID5A 
               
               
                 8 
                 ENSG00000196954 
                 CASP4 
               
               
                 8 
                 ENSG00000197081 
                 IGF2R 
               
               
                 8 
                 ENSG00000197249 
                 SERPINA1 
               
               
                 8 
                 ENSG00000197471 
                 SPN 
               
               
                 8 
                 ENSG00000197629 
                 MPEG1 
               
               
                 8 
                 ENSG00000197860 
                 SGTB 
               
               
                 8 
                 ENSG00000197872 
                 FAM49A 
               
               
                 8 
                 ENSG00000198053 
                 SIRPA 
               
               
                 8 
                 ENSG00000198223 
                 CSF2RA 
               
               
                 8 
                 ENSG00000198286 
                 CARD11 
               
               
                 8 
                 ENSG00000198771 
                 RCSD1 
               
               
                 8 
                 ENSG00000198821 
                 CD247 
               
               
                 8 
                 ENSG00000198837 
                 DENND4B 
               
               
                 8 
                 ENSG00000198846 
                 TOX 
               
               
                 8 
                 ENSG00000198851 
                 CD3E 
               
               
                 8 
                 ENSG00000198879 
                 SFMBT2 
               
               
                 8 
                 ENSG00000203747 
                 FCGR3A 
               
               
                 8 
                 ENSG00000204136 
                 GGTA1P 
               
               
                 8 
                 ENSG00000204160 
                 ZDHHC18 
               
               
                 8 
                 ENSG00000204267 
                 TAP2 
               
               
                 8 
                 ENSG00000204397 
                 CARD16 
               
               
                 8 
                 ENSG00000204472 
                 AIF1 
               
               
                 8 
                 ENSG00000204482 
                 LST1 
               
               
                 8 
                 ENSG00000204516 
                 MICB 
               
               
                 8 
                 ENSG00000204577 
                 LILRB3 
               
               
                 8 
                 ENSG00000204947 
                 ZNF425 
               
               
                 8 
                 ENSG00000205269 
                 TMEM170B 
               
               
                 8 
                 ENSG00000205744 
                 DENND1C 
               
               
                 8 
                 ENSG00000211689 
                 TRGC1 
               
               
                 8 
                 ENSG00000213203 
                 GIMAP1 
               
               
                 8 
                 ENSG00000213402 
                 PTPRCAP 
               
               
                 8 
                 ENSG00000213445 
                 SIPA1 
               
               
                 8 
                 ENSG00000213654 
                 GPSM3 
               
               
                 8 
                 ENSG00000213658 
                 LAT 
               
               
                 8 
                 ENSG00000213809 
                 KLRK1 
               
               
                 8 
                 ENSG00000215114 
                 UBXN2B 
               
               
                 8 
                 ENSG00000216490 
                 IFI30 
               
               
                 8 
                 ENSG00000217128 
                 FNIP1 
               
               
                 8 
                 ENSG00000217555 
                 CKLF 
               
               
                 8 
                 ENSG00000224397 
               
               
                 8 
                 ENSG00000227191 
                 TRGC2 
               
               
                 8 
                 ENSG00000227507 
                 LTB 
               
               
                 8 
                 ENSG00000229164 
                 TRAC 
               
               
                 8 
                 ENSG00000229644 
                 NAMPTL 
               
               
                 8 
                 ENSG00000235568 
                 NFAM1 
               
               
                 8 
                 ENSG00000239998 
                 LILRA2 
               
               
                 8 
                 ENSG00000241839 
                 PLEKHO2 
               
               
                 8 
                 ENSG00000241878 
                 PISD 
               
               
                 8 
                 ENSG00000242539 
               
               
                 8 
                 ENSG00000244482 
                 LILRA6 
               
               
                 8 
                 ENSG00000247774 
                 PCED1B-AS1 
               
               
                 8 
                 ENSG00000250264 
               
               
                 8 
                 ENSG00000255398 
                 HCAR3 
               
               
                 8 
                 ENSG00000256007 
                 ARAP1-AS1 
               
               
                 8 
                 ENSG00000258227 
                 CLEC5A 
               
               
                 8 
                 ENSG00000265206 
                 MIR142 
               
               
                 8 
                 ENSG00000267121 
               
               
                 8 
                 ENSG00000268001 
               
               
                 8 
                 ENSG00000269215 
               
               
                 8 
                 ENSG00000269728 
               
               
                 9 
                 ENSG00000002549 
                 LAP3 
               
               
                 9 
                 ENSG00000013374 
                 NUB1 
               
               
                 9 
                 ENSG00000019582 
                 CD74 
               
               
                 9 
                 ENSG00000026950 
                 BTN3A1 
               
               
                 9 
                 ENSG00000055332 
                 EIF2AK2 
               
               
                 9 
                 ENSG00000059378 
                 PARP12 
               
               
                 9 
                 ENSG00000067066 
                 SP100 
               
               
                 9 
                 ENSG00000068079 
                 IF135 
               
               
                 9 
                 ENSG00000089692 
                 LAG3 
               
               
                 9 
                 ENSG00000092010 
                 PSME1 
               
               
                 9 
                 ENSG00000100336 
                 APOL4 
               
               
                 9 
                 ENSG00000100342 
                 APOL1 
               
               
                 9 
                 ENSG00000100911 
                 PSME2 
               
               
                 9 
                 ENSG00000106785 
                 TRIM14 
               
               
                 9 
                 ENSG00000107201 
                 DDX58 
               
               
                 9 
                 ENSG00000111331 
                 OAS3 
               
               
                 9 
                 ENSG00000111335 
                 OAS2 
               
               
                 9 
                 ENSG00000111801 
                 BTN3A3 
               
               
                 9 
                 ENSG00000112763 
                 BTN2A1 
               
               
                 9 
                 ENSG00000114127 
                 XRN1 
               
               
                 9 
                 ENSG00000115267 
                 IFIH1 
               
               
                 9 
                 ENSG00000115415 
                 STAT1 
               
               
                 9 
                 ENSG00000117228 
                 GBP1 
               
               
                 9 
                 ENSG00000119917 
                 IFIT3 
               
               
                 9 
                 ENSG00000121858 
                 TNFSF10 
               
               
                 9 
                 ENSG00000123240 
                 OPTN 
               
               
                 9 
                 ENSG00000123609 
                 NMI 
               
               
                 9 
                 ENSG00000124201 
                 ZNFX1 
               
               
                 9 
                 ENSG00000124226 
                 RNF114 
               
               
                 9 
                 ENSG00000124508 
                 BTN2A2 
               
               
                 9 
                 ENSG00000125347 
                 IRF1 
               
               
                 9 
                 ENSG00000126709 
                 IFI6 
               
               
                 9 
                 ENSG00000128284 
                 APOL3 
               
               
                 9 
                 ENSG00000128335 
                 APOL2 
               
               
                 9 
                 ENSG00000130303 
                 BST2 
               
               
                 9 
                 ENSG00000130487 
                 KLHDC7B 
               
               
                 9 
                 ENSG00000130589 
                 HELZ2 
               
               
                 9 
                 ENSG00000131203 
                 IDO1 
               
               
                 9 
                 ENSG00000132109 
                 TRIM21 
               
               
                 9 
                 ENSG00000132274 
                 TRIM22 
               
               
                 9 
                 ENSG00000133106 
                 EPSTI1 
               
               
                 9 
                 ENSG00000134326 
                 CMPK2 
               
               
                 9 
                 ENSG00000135148 
                 TRAFD1 
               
               
                 9 
                 ENSG00000136816 
                 TOR1B 
               
               
                 9 
                 ENSG00000137628 
                 DDX60 
               
               
                 9 
                 ENSG00000137959 
                 IFI44L 
               
               
                 9 
                 ENSG00000137965 
                 IFI44 
               
               
                 9 
                 ENSG00000138496 
                 PARP9 
               
               
                 9 
                 ENSG00000138642 
                 HERC6 
               
               
                 9 
                 ENSG00000138755 
                 CXCL9 
               
               
                 9 
                 ENSG00000140105 
                 WARS 
               
               
                 9 
                 ENSG00000140464 
                 PML 
               
               
                 9 
                 ENSG00000140853 
                 NLRC5 
               
               
                 9 
                 ENSG00000152778 
                 IFIT5 
               
               
                 9 
                 ENSG00000156587 
                 UBE2L6 
               
               
                 9 
                 ENSG00000157601 
                 MX1 
               
               
                 9 
                 ENSG00000158773 
                 USF1 
               
               
                 9 
                 ENSG00000160710 
                 ADAR 
               
               
                 9 
                 ENSG00000160932 
                 LY6E 
               
               
                 9 
                 ENSG00000162654 
                 GBP4 
               
               
                 9 
                 ENSG00000163840 
                 DTX3L 
               
               
                 9 
                 ENSG00000164136 
                 IL15 
               
               
                 9 
                 ENSG00000165949 
                 IFI27 
               
               
                 9 
                 ENSG00000166278 
                 C2 
               
               
                 9 
                 ENSG00000166710 
                 B2M 
               
               
                 9 
                 ENSG00000168062 
                 BATF2 
               
               
                 9 
                 ENSG00000168394 
                 TAP1 
               
               
                 9 
                 ENSG00000168961 
                 LGALS9 
               
               
                 9 
                 ENSG00000169245 
                 CXCL10 
               
               
                 9 
                 ENSG00000173193 
                 PARP14 
               
               
                 9 
                 ENSG00000173821 
                 RNF213 
               
               
                 9 
                 ENSG00000177409 
                 SAMD9L 
               
               
                 9 
                 ENSG00000179344 
                 HLA-DQB1 
               
               
                 9 
                 ENSG00000179583 
                 CIITA 
               
               
                 9 
                 ENSG00000185338 
                 SOCS1 
               
               
                 9 
                 ENSG00000185404 
                 SP140L 
               
               
                 9 
                 ENSG00000185880 
                 TRIM69 
               
               
                 9 
                 ENSG00000186470 
                 BTN3A2 
               
               
                 9 
                 ENSG00000187608 
                 ISG15 
               
               
                 9 
                 ENSG00000188282 
                 RUFY4 
               
               
                 9 
                 ENSG00000188313 
                 PLSCR1 
               
               
                 9 
                 ENSG00000196126 
                 HLA-DRB1 
               
               
                 9 
                 ENSG00000196735 
                 HLA-DQA1 
               
               
                 9 
                 ENSG00000197142 
                 ACSL5 
               
               
                 9 
                 ENSG00000197536 
                 C5orf56 
               
               
                 9 
                 ENSG00000204252 
                 HLA-DOA 
               
               
                 9 
                 ENSG00000204257 
                 HLA-DMA 
               
               
                 9 
                 ENSG00000204261 
                 TAPSAR1 
               
               
                 9 
                 ENSG00000204264 
                 PSMB8 
               
               
                 9 
                 ENSG00000204287 
                 HLA-DRA 
               
               
                 9 
                 ENSG00000204525 
                 HLA-C 
               
               
                 9 
                 ENSG00000204592 
                 HLA-E 
               
               
                 9 
                 ENSG00000204642 
                 HLA-F 
               
               
                 9 
                 ENSG00000205220 
                 PSMB10 
               
               
                 9 
                 ENSG00000205436 
                 EXOC3L4 
               
               
                 9 
                 ENSG00000206337 
                 HCP5 
               
               
                 9 
                 ENSG00000206503 
                 HLA-A 
               
               
                 9 
                 ENSG00000213886 
                 UBD 
               
               
                 9 
                 ENSG00000213928 
                 IRF9 
               
               
                 9 
                 ENSG00000221963 
                 APOL6 
               
               
                 9 
                 ENSG00000223865 
                 HLA-DPB1 
               
               
                 9 
                 ENSG00000225131 
                 PSME2P2 
               
               
                 9 
                 ENSG00000225492 
                 GBP1P1 
               
               
                 9 
                 ENSG00000231389 
                 HLA-DPA1 
               
               
                 9 
                 ENSG00000231925 
                 TAPBP 
               
               
                 9 
                 ENSG00000232629 
                 HLA-DQB2 
               
               
                 9 
                 ENSG00000234745 
                 HLA-B 
               
               
                 9 
                 ENSG00000237988 
                 OR2I1P 
               
               
                 9 
                 ENSG00000240065 
                 PSMB9 
               
               
                 9 
                 ENSG00000242574 
                 HLA-DMB 
               
               
                 9 
                 ENSG00000263013 
               
               
                 9 
                 ENSG00000269640 
               
               
                 10 
                 ENSG00000167535 
                 CACNB3 
               
               
                 10 
                 ENSG00000109339 
                 MAPK10 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14 
               
             
            
               
                   
               
               
                 22 genes that were selected from the 3,936 to predict the molecular  
               
               
                 subtypes in the Validation Cohort (endobronchial biopsies) 
               
            
           
           
               
               
               
            
               
                 Gene 
                   
                   
               
               
                 Module 
                 Gene Name 
                 EnsemblID 
               
               
                   
               
               
                 1 
                 PHLDB1 
                 ENSG00000019144 
               
               
                 1 
                 MARVELD1 
                 ENSG00000155254 
               
               
                 1 
                 KIRREL1 
                 ENSG00000183853 
               
               
                 2 
                 CCNL2 
                 ENSG00000221978 
               
               
                 2 
                 MSANTD2 
                 ENSG00000120458 
               
               
                 2 
                 LUC7L 
                 ENSG00000007392 
               
               
                 3 
                 BTG2 
                 ENSG00000159388 
               
               
                 3 
                 ZFP36 
                 ENSG00000128016 
               
               
                 4 
                 COX6A1 
                 ENSG00000111775 
               
               
                 4 
                 COX7A2 
                 ENSG00000112695 
               
               
                 5 
                 RACGAP1 
                 ENSG00000161800 
               
               
                 5 
                 TPX2 
                 ENSG00000088325 
               
               
                 6 
                 NEK11 
                 ENSG00000114670 
               
               
                 6 
                 IFT88 
                 ENSG00000032742 
               
               
                 7 
                 RPL26 
                 ENSG00000161970 
               
               
                 7 
                 RPL23 
                 ENSG00000125691 
               
               
                 8 
                 DOCK2 
                 ENSG00000134516 
               
               
                 8 
                 CD53 
                 ENSG00000143119 
               
               
                 8 
                 LAPTM5 
                 ENSG00000162511 
               
               
                 9 
                 UBE2L6 
                 ENSG00000156587 
               
               
                 9 
                 EPSTI1 
                 ENSG00000133106 
               
               
                 9 
                 TAP1 
                 ENSG00000168394 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                 8 genes that were selected out of the 22 genes (Table 14) to  
               
               
                 predict the Proliferative subtype or not in the bronchial brushes 
               
            
           
           
               
               
               
               
            
               
                   
                 Gene 
                   
                   
               
               
                   
                 Module 
                 Gene Name 
                 EnsemblID 
               
               
                   
                   
               
               
                   
                 4 
                 COX6A1 
                 ENSG00000111775 
               
               
                   
                 4 
                 COX7A2 
                 ENSG00000112695 
               
               
                   
                 5 
                 RACGAP1 
                 ENSG00000161800 
               
               
                   
                 5 
                 TPX2 
                 ENSG00000088325 
               
               
                   
                 6 
                 NEK11 
                 ENSG00000114670 
               
               
                   
                 6 
                 IFT88 
                 ENSG00000032742 
               
               
                   
                 7 
                 RPL26 
                 ENSG00000161970 
               
               
                   
                 7 
                 RPL23 
                 ENSG00000125691 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16 
               
             
            
               
                   
               
               
                 112 genes used to predict progression/persistence versus  
               
               
                 regression in endobronchial biopsies classified to be in the  
               
               
                 Proliferative subtype. Genes in Module 9 associated with 
               
               
                 progression/regression. These genes are contained within Table 13. 
               
            
           
           
               
               
               
            
               
                   
                 EnsemblID 
                 GeneSymbols 
               
               
                   
                   
               
               
                   
                 ENSG00000002549 
                 LAP3 
               
               
                   
                 ENSG00000013374 
                 NUB1 
               
               
                   
                 ENSG00000019582 
                 CD74 
               
               
                   
                 ENSG00000026950 
                 BTN3A1 
               
               
                   
                 ENSG00000055332 
                 EIF2AK2 
               
               
                   
                 ENSG00000059378 
                 PARP12 
               
               
                   
                 ENSG00000067066 
                 SP100 
               
               
                   
                 ENSG00000068079 
                 IFI35 
               
               
                   
                 ENSG00000089692 
                 LAG3 
               
               
                   
                 ENSG00000092010 
                 PSME1 
               
               
                   
                 ENSG00000100336 
                 APOL4 
               
               
                   
                 ENSG00000100342 
                 APOL1 
               
               
                   
                 ENSG00000100911 
                 PSME2 
               
               
                   
                 ENSG00000106785 
                 TRIM14 
               
               
                   
                 ENSG00000107201 
                 DDX58 
               
               
                   
                 ENSG00000111331 
                 OAS3 
               
               
                   
                 ENSG00000111335 
                 OAS2 
               
               
                   
                 ENSG00000111801 
                 BTN3A3 
               
               
                   
                 ENSG00000112763 
                 BTN2A1 
               
               
                   
                 ENSG00000114127 
                 XRN1 
               
               
                   
                 ENSG00000115267 
                 IFIH1 
               
               
                   
                 ENSG00000115415 
                 STAT1 
               
               
                   
                 ENSG00000117228 
                 GBP1 
               
               
                   
                 ENSG00000119917 
                 IFIT3 
               
               
                   
                 ENSG00000121858 
                 TNFSF10 
               
               
                   
                 ENSG00000123240 
                 OPTN 
               
               
                   
                 ENSG00000123609 
                 NMI 
               
               
                   
                 ENSG00000124201 
                 ZNFX1 
               
               
                   
                 ENSG00000124226 
                 RNF114 
               
               
                   
                 ENSG00000124508 
                 BTN2A2 
               
               
                   
                 ENSG00000125347 
                 IRF1 
               
               
                   
                 ENSG00000126709 
                 IFI6 
               
               
                   
                 ENSG00000128284 
                 APOL3 
               
               
                   
                 ENSG00000128335 
                 APOL2 
               
               
                   
                 ENSG00000130303 
                 BST2 
               
               
                   
                 ENSG00000130487 
                 KLHDC7B 
               
               
                   
                 ENSG00000130589 
                 HELZ2 
               
               
                   
                 ENSG00000131203 
                 IDO1 
               
               
                   
                 ENSG00000132109 
                 TRIM21 
               
               
                   
                 ENSG00000132274 
                 TRIM22 
               
               
                   
                 ENSG00000133106 
                 EPSTI1 
               
               
                   
                 ENSG00000134326 
                 CMPK2 
               
               
                   
                 ENSG00000135148 
                 TRAFD1 
               
               
                   
                 ENSG00000136816 
                 TOR1B 
               
               
                   
                 ENSG00000137628 
                 DDX60 
               
               
                   
                 ENSG00000137959 
                 IFI44L 
               
               
                   
                 ENSG00000137965 
                 IFI44 
               
               
                   
                 ENSG00000138496 
                 PARP9 
               
               
                   
                 ENSG00000138642 
                 HERC6 
               
               
                   
                 ENSG00000138755 
                 CXCL9 
               
               
                   
                 ENSG00000140105 
                 WARS 
               
               
                   
                 ENSG00000140464 
                 PML 
               
               
                   
                 ENSG00000140853 
                 NLRC5 
               
               
                   
                 ENSG00000152778 
                 IFIT5 
               
               
                   
                 ENSG00000156587 
                 UBE2L6 
               
               
                   
                 ENSG00000157601 
                 MX1 
               
               
                   
                 ENSG00000158773 
                 USF1 
               
               
                   
                 ENSG00000160710 
                 ADAR 
               
               
                   
                 ENSG00000160932 
                 LY6E 
               
               
                   
                 ENSG00000162654 
                 GBP4 
               
               
                   
                 ENSG00000163840 
                 DTX3L 
               
               
                   
                 ENSG00000164136 
                 IL15 
               
               
                   
                 ENSG00000165949 
                 IFI27 
               
               
                   
                 ENSG00000166278 
                 C2 
               
               
                   
                 ENSG00000166710 
                 B2M 
               
               
                   
                 ENSG00000168062 
                 BATF2 
               
               
                   
                 ENSG00000168394 
                 TAP1 
               
               
                   
                 ENSG00000168961 
                 LGALS9 
               
               
                   
                 ENSG00000169245 
                 CXCL10 
               
               
                   
                 ENSG00000173193 
                 PARP14 
               
               
                   
                 ENSG00000173821 
                 RNF213 
               
               
                   
                 ENSG00000177409 
                 SAMD9L 
               
               
                   
                 ENSG00000179344 
                 HLA-DQB1 
               
               
                   
                 ENSG00000179583 
                 CIITA 
               
               
                   
                 ENSG00000185338 
                 SOCS1 
               
               
                   
                 ENSG00000185404 
                 SP140L 
               
               
                   
                 ENSG00000185880 
                 TRIM69 
               
               
                   
                 ENSG00000186470 
                 BTN3A2 
               
               
                   
                 ENSG00000187608 
                 ISG15 
               
               
                   
                 ENSG00000188282 
                 RUFY4 
               
               
                   
                 ENSG00000188313 
                 PLSCR1 
               
               
                   
                 ENSG00000196126 
                 HLA-DRB1 
               
               
                   
                 ENSG00000196735 
                 HLA-DQA1 
               
               
                   
                 ENSG00000197142 
                 ACSL5 
               
               
                   
                 ENSG00000197536 
                 C5orf56 
               
               
                   
                 ENSG00000204252 
                 HLA-DOA 
               
               
                   
                 ENSG00000204257 
                 HLA-DMA 
               
               
                   
                 ENSG00000204261 
                 TAPSAR1 
               
               
                   
                 ENSG00000204264 
                 PSMB8 
               
               
                   
                 ENSG00000204287 
                 HLA-DRA 
               
               
                   
                 ENSG00000204525 
                 HLA-C 
               
               
                   
                 ENSG00000204592 
                 HLA-E 
               
               
                   
                 ENSG00000204642 
                 HLA-F 
               
               
                   
                 ENSG00000205220 
                 PSMB10 
               
               
                   
                 ENSG00000205436 
                 EXOC3L4 
               
               
                   
                 ENSG00000206337 
                 HCP5 
               
               
                   
                 ENSG00000206503 
                 HLA-A 
               
               
                   
                 ENSG00000213886 
                 UBD 
               
               
                   
                 ENSG00000213928 
                 IRF9 
               
               
                   
                 ENSG00000221963 
                 APOL6 
               
               
                   
                 ENSG00000223865 
                 HLA-DPB1 
               
               
                   
                 ENSG00000225131 
                 PSME2P2 
               
               
                   
                 ENSG00000225492 
                 GBP1P1 
               
               
                   
                 ENSG00000231389 
                 HLA-DPA1 
               
               
                   
                 ENSG00000231925 
                 TAPBP 
               
               
                   
                 ENSG00000232629 
                 HLA-DQB2 
               
               
                   
                 ENSG00000234745 
                 HLA-B 
               
               
                   
                 ENSG00000237988 
                 OR2I1P 
               
               
                   
                 ENSG00000240065 
                 PSMB9 
               
               
                   
                 ENSG00000242574 
                 HLA-DMB 
               
               
                   
                 ENSG00000263013 
                 RP11-876N24.5 
               
               
                   
                 ENSG00000269640 
               
               
                   
                   
               
            
           
         
       
     
     The methods described herein relate to the determination of the expression level of at least one gene. In some embodiments of any of the aspects, the at least one gene can be one or more genes selected from Tables 13, 14, 15, and/or 16. In some embodiments of any of the aspects, the gene lists of Tables 13, 14 and 16 are relevant to endobronchial biopsy samples that range in histology from normal to premalignant. In some embodiments of any of the aspects, where the sample is an endobronchial biopsy sample, the one or more genes are selected from Table 13, 14 and/or 16. In some embodiments of any of the aspects, Table 15 is relevant for normal bronchial brushings. In some embodiments of any of the aspects, where the sample is bronchial brushing sample (e.g, of normal tissue), the one or more genes are selected from Table 15. 
     In some embodiments of any of the aspects, the one or more genes selected from Table 13 or 16 are not B2M, HLA-DRA, HLA-DRB1, or HLA-DPA1. In some embodiments of any of the aspects, if the one or more genes selected from Table 13 or 16 include B2M, HLA-DRA, HLA-DRB1, and/or HLA-DPA1, at least one additional gene from Table 13 or 16 is selected. 
     For convenience, the meaning of some terms and phrases used in the specification, examples, and appended claims, are provided below. Unless stated otherwise, or implicit from context, the following terms and phrases include the meanings provided below. The definitions are provided to aid in describing particular embodiments, and are not intended to limit the claimed invention, because the scope of the invention is limited only by the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. If there is an apparent discrepancy between the usage of a term in the art and its definition provided herein, the definition provided within the specification shall prevail. 
     For convenience, certain terms employed herein, in the specification, examples and appended claims are collected here. 
     As used herein, the term “cancer” relates generally to a class of diseases or conditions in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. 
     In some embodiments of any of the aspects, the cancer is a primary cancer. In some embodiments of any of the aspects, the cancer is a malignant cancer. As used herein, the term “malignant” refers to a cancer in which a group of tumor cells display one or more of uncontrolled growth (i.e., division beyond normal limits), invasion (i.e., intrusion on and destruction of adjacent tissues), and metastasis (i.e., spread to other locations in the body via lymph or blood). As used herein, the term “metastasize” refers to the spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. As used herein, the term “benign” or “non-malignant” refers to tumors that may grow larger but do not spread to other parts of the body. Benign tumors are self-limited and typically do not invade or metastasize. 
     A “cancer cell” or “tumor cell” refers to an individual cell of a cancerous growth or tissue. A tumor refers generally to a swelling or lesion formed by an abnormal growth of cells, which may be benign, pre-malignant, or malignant. Most cancer cells form tumors, but some, e.g., leukemia, do not necessarily form tumors. For those cancer cells that form tumors, the terms cancer (cell) and tumor (cell) are used interchangeably. 
     As used herein the term “neoplasm” refers to any new and abnormal growth of tissue, e.g., an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues. Thus, a neoplasm can be a benign neoplasm, premalignant neoplasm, or a malignant neoplasm. 
     A subject that has a cancer or a tumor is a subject having objectively measurable cancer cells present in the subject&#39;s body. Included in this definition are malignant, actively proliferative cancers, as well as potentially dormant tumors or micrometastatses. Cancers which migrate from their original location and seed other vital organs can eventually lead to the death of the subject through the functional deterioration of the affected organs. 
     Examples of cancer include but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, leukemia, basal cell carcinoma, biliary tract cancer; bladder cancer; bone cancer; brain and CNS cancer; breast cancer; cancer of the peritoneum; cervical cancer; choriocarcinoma; colon and rectum cancer; connective tissue cancer; cancer of the digestive system; endometrial cancer; esophageal cancer; eye cancer; cancer of the head and neck; gastric cancer (including gastrointestinal cancer); glioblastoma (GBM); hepatic carcinoma; hepatoma; intra-epithelial neoplasm.; kidney or renal cancer; larynx cancer; leukemia; liver cancer; lung cancer (e.g., small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung); lymphoma including Hodgkin&#39;s and non-Hodgkin&#39;s lymphoma; melanoma; myeloma; neuroblastoma; oral cavity cancer (e.g., lip, tongue, mouth, and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rhabdomyosarcoma; rectal cancer; cancer of the respiratory system; salivary gland carcinoma; sarcoma; skin cancer; squamous cell cancer; stomach cancer; testicular cancer; thyroid cancer; uterine or endometrial cancer; cancer of the urinary system; vulval cancer; as well as other carcinomas and sarcomas; as well as B-cell lymphoma (including low grade/follicular non-Hodgkin&#39;s lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade/follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenstrom&#39;s Macroglobulinemia); chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); Hairy cell leukemia; chronic myeloblastic leukemia; and post-transplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with phakomatoses, edema (such as that associated with brain tumors), and Meigs&#39; syndrome 
     A “cancer cell” is a cancerous, pre-cancerous, or transformed cell, either in vivo, ex vivo, or in tissue culture, that has spontaneous or induced phenotypic changes that do not necessarily involve the uptake of new genetic material. Although transformation can arise from infection with a transforming virus and incorporation of new genomic nucleic acid, or uptake of exogenous nucleic acid, it can also arise spontaneously or following exposure to a carcinogen, thereby mutating an endogenous gene. Transformation/cancer is associated with, e.g., morphological changes, immortalization of cells, aberrant growth control, foci formation, anchorage independence, malignancy, loss of contact inhibition and density limitation of growth, growth factor or serum independence, tumor specific markers, invasiveness or metastasis, and tumor growth in suitable animal hosts such as nude mice. 
     The terms “decrease”, “reduced”, “reduction”, or “inhibit” are all used herein to mean a decrease by a statistically significant amount. In some embodiments, “reduce,” “reduction” or “decrease” or “inhibit” typically means a decrease by at least 10% as compared to a reference level (e.g. the absence of a given treatment or agent) and can include, for example, a decrease by at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or more. As used herein, “reduction” or “inhibition” does not encompass a complete inhibition or reduction as compared to a reference level. “Complete inhibition” is a 100% inhibition as compared to a reference level. A decrease can be preferably down to a level accepted as within the range of normal for an individual without a given disorder. 
     The terms “increased”, “increase”, “enhance”, or “activate” are all used herein to mean an increase by a statically significant amount. In some embodiments, the terms “increased”, “increase”, “enhance”, or “activate” can mean an increase of at least 10% as compared to a reference level, for example an increase of at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90% or up to and including a 100% increase or any increase between 10-100% as compared to a reference level, or at least about a 2-fold, or at least about a 3-fold, or at least about a 4-fold, or at least about a 5-fold or at least about a 10-fold increase, or any increase between 2-fold and 10-fold or greater as compared to a reference level. In the context of a marker or symptom, a “increase” is a statistically significant increase in such level. 
     As used herein, a “subject” means a human or animal. Usually the animal is a vertebrate such as a primate, rodent, domestic animal or game animal. Primates include chimpanzees, cynomologous monkeys, spider monkeys, and macaques, e.g., Rhesus. Rodents include mice, rats, woodchucks, ferrets, rabbits and hamsters. Domestic and game animals include cows, horses, pigs, deer, bison, buffalo, feline species, e.g., domestic cat, canine species, e.g., dog, fox, wolf, avian species, e.g., chicken, emu, ostrich, and fish, e.g., trout, catfish and salmon. In some embodiments, the subject is a mammal, e.g., a primate, e.g., a human. The terms, “individual,” “patient” and “subject” are used interchangeably herein. 
     Preferably, the subject is a mammal. The mammal can be a human, non-human primate, mouse, rat, dog, cat, horse, or cow, but is not limited to these examples. Mammals other than humans can be advantageously used as subjects that represent animal models of bronchial premalignant lesions. A subject can be male or female. 
     A subject can be one who has been previously diagnosed with or identified as suffering from or having a condition in need of treatment (e.g. bronchial premalignant lesions) or one or more complications related to such a condition, and optionally, have already undergone treatment for bronchial premalignant lesions or the one or more complications related to bronchial premalignant lesions. Alternatively, a subject can also be one who has not been previously diagnosed as having bronchial premalignant lesions or one or more complications related to bronchial premalignant lesions. For example, a subject can be one who exhibits one or more risk factors for bronchial premalignant lesions or one or more complications related to bronchial premalignant lesions or a subject who does not exhibit risk factors. 
     A “subject in need” of treatment for a particular condition can be a subject having that condition, diagnosed as having that condition, or at risk of developing that condition. 
     As used herein, the terms “protein” and “polypeptide” are used interchangeably herein to designate a series of amino acid residues, connected to each other by peptide bonds between the alpha-amino and carboxy groups of adjacent residues. The terms “protein”, and “polypeptide” refer to a polymer of amino acids, including modified amino acids (e.g., phosphorylated, glycated, glycosylated, etc.) and amino acid analogs, regardless of its size or function. “Protein” and “polypeptide” are often used in reference to relatively large polypeptides, whereas the term “peptide” is often used in reference to small polypeptides, but usage of these terms in the art overlaps. The terms “protein” and “polypeptide” are used interchangeably herein when referring to a gene product and fragments thereof. Thus, exemplary polypeptides or proteins include gene products, naturally occurring proteins, homologs, orthologs, paralogs, fragments and other equivalents, variants, fragments, and analogs of the foregoing. 
     In the various embodiments described herein, it is further contemplated that variants (naturally occurring or otherwise), alleles, homologs, conservatively modified variants, and/or conservative substitution variants of any of the particular polypeptides described are encompassed. As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters a single amino acid or a small percentage of amino acids in the encoded sequence is a “conservatively modified variant” where the alteration results in the substitution of an amino acid with a chemically similar amino acid and retains the desired activity of the polypeptide. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles consistent with the disclosure. 
     A given amino acid can be replaced by a residue having similar physiochemical characteristics, e.g., substituting one aliphatic residue for another (such as Ile, Val, Leu, or Ala for one another), or substitution of one polar residue for another (such as between Lys and Arg; Glu and Asp; or Gln and Asn). Other such conservative substitutions, e.g., substitutions of entire regions having similar hydrophobicity characteristics, are well known. Polypeptides comprising conservative amino acid substitutions can be tested in any one of the assays described herein to confirm that a desired activity, e.g. activity and specificity of a native or reference polypeptide is retained. 
     Amino acids can be grouped according to similarities in the properties of their side chains (in A. L. Lehninger, in Biochemistry, second ed., pp. 73-75, Worth Publishers, New York (1975)): (1) non-polar: Ala (A), Val (V), Leu (L), Ile (I), Pro (P), Phe (F), Trp (W), Met (M); (2) uncharged polar: Gly (G), Ser (S), Thr (T), Cys (C), Tyr (Y), Asn (N), Gln (Q); (3) acidic: Asp (D), Glu (E); (4) basic: Lys (K), Arg (R), His (H). Alternatively, naturally occurring residues can be divided into groups based on common side-chain properties: (1) hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that influence chain orientation: Gly, Pro; (6) aromatic: Trp, Tyr, Phe. Non-conservative substitutions will entail exchanging a member of one of these classes for another class. Particular conservative substitutions include, for example; Ala into Gly or into Ser; Arg into Lys; Asn into Gln or into His; Asp into Glu; Cys into Ser; Gln into Asn; Glu into Asp; Gly into Ala or into Pro; His into Asn or into Gln; Ile into Leu or into Val; Leu into Ile or into Val; Lys into Arg, into Gln or into Glu; Met into Leu, into Tyr or into Ile; Phe into Met, into Leu or into Tyr; Ser into Thr; Thr into Ser; Trp into Tyr; Tyr into Trp; and/or Phe into Val, into Ile or into Leu. 
     In some embodiments, the polypeptide described herein (or a nucleic acid encoding such a polypeptide) can be a functional fragment of one of the amino acid sequences described herein. As used herein, a “functional fragment” is a fragment or segment of a peptide which retains at least 50% of the wildtype reference polypeptide&#39;s activity according to the assays described below herein. A functional fragment can comprise conservative substitutions of the sequences disclosed herein. 
     In some embodiments, the polypeptide described herein can be a variant of a sequence described herein. In some embodiments, the variant is a conservatively modified variant. Conservative substitution variants can be obtained by mutations of native nucleotide sequences, for example. A “variant,” as referred to herein, is a polypeptide substantially homologous to a native or reference polypeptide, but which has an amino acid sequence different from that of the native or reference polypeptide because of one or a plurality of deletions, insertions or substitutions. Variant polypeptide-encoding DNA sequences encompass sequences that comprise one or more additions, deletions, or substitutions of nucleotides when compared to a native or reference DNA sequence, but that encode a variant protein or fragment thereof that retains activity. A wide variety of PCR-based site-specific mutagenesis approaches are known in the art and can be applied by the ordinarily skilled artisan. 
     A variant amino acid or DNA sequence can be at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more, identical to a native or reference sequence. The degree of homology (percent identity) between a native and a mutant sequence can be determined, for example, by comparing the two sequences using freely available computer programs commonly employed for this purpose on the world wide web (e.g. BLASTp or BLASTn with default settings). 
     Alterations of the native amino acid sequence can be accomplished by any of a number of techniques known to one of skill in the art. Mutations can be introduced, for example, at particular loci by synthesizing oligonucleotides containing a mutant sequence, flanked by restriction sites enabling ligation to fragments of the native sequence. Following ligation, the resulting reconstructed sequence encodes an analog having the desired amino acid insertion, substitution, or deletion. Alternatively, oligonucleotide-directed site-specific mutagenesis procedures can be employed to provide an altered nucleotide sequence having particular codons altered according to the substitution, deletion, or insertion required. Techniques for making such alterations are very well established and include, for example, those disclosed by Walder et al. (Gene 42:133, 1986); Bauer et al. (Gene 37:73, 1985); Craik (BioTechniques, January 1985, 12-19); Smith et al. (Genetic Engineering: Principles and Methods, Plenum Press, 1981); and U.S. Pat. Nos. 4,518,584 and 4,737,462, which are herein incorporated by reference in their entireties. Any cysteine residue not involved in maintaining the proper conformation of the polypeptide also can be substituted, generally with serine, to improve the oxidative stability of the molecule and prevent aberrant crosslinking. Conversely, cysteine bond(s) can be added to the polypeptide to improve its stability or facilitate oligomerization. 
     As used herein, the term “nucleic acid” or “nucleic acid sequence” refers to any molecule, preferably a polymeric molecule, incorporating units of ribonucleic acid, deoxyribonucleic acid or an analog thereof. The nucleic acid can be either single-stranded or double-stranded. A single-stranded nucleic acid can be one nucleic acid strand of a denatured double-stranded DNA. Alternatively, it can be a single-stranded nucleic acid not derived from any double-stranded DNA. In one aspect, the nucleic acid can be DNA. In another aspect, the nucleic acid can be RNA. Suitable DNA can include, e.g., genomic DNA or cDNA. Suitable RNA can include, e.g., mRNA. 
     The term “expression” refers to the cellular processes involved in producing RNA and proteins and as appropriate, secreting proteins, including where applicable, but not limited to, for example, transcription, transcript processing, translation and protein folding, modification and processing. Expression can refer to the transcription and stable accumulation of sense (mRNA) or antisense RNA derived from a nucleic acid fragment or fragments of the invention and/or to the translation of mRNA into a polypeptide. 
     In some embodiments, the expression of a biomarker(s), target(s), or gene/polypeptide described herein is/are tissue-specific. In some embodiments, the expression of a biomarker(s), target(s), or gene/polypeptide described herein is/are global. In some embodiments, the expression of a biomarker(s), target(s), or gene/polypeptide described herein is systemic. 
     “Expression products” include RNA transcribed from a gene, and polypeptides obtained by translation of mRNA transcribed from a gene. The term “gene” means the nucleic acid sequence which is transcribed (DNA) to RNA in vitro or in vivo when operably linked to appropriate regulatory sequences. The gene may or may not include regions preceding and following the coding region, e.g. 5′ untranslated (5′UTR) or “leader” sequences and 3′ UTR or “trailer” sequences, as well as intervening sequences (introns) between individual coding segments (exons). 
     “Marker” in the context of the present invention refers to an expression product, e.g., nucleic acid or polypeptide which is differentially present in a sample taken from subjects having bronchial premalignant lesions of a particular subtype, as compared to a comparable sample taken from control subjects (e.g., a healthy subject). The term “biomarker” is used interchangeably with the term “marker.” 
     In some embodiments, the methods described herein relate to measuring, detecting, or determining the level of at least one marker. As used herein, the term “detecting” or “measuring” refers to observing a signal from, e.g. a probe, label, or target molecule to indicate the presence of an analyte in a sample. Any method known in the art for detecting a particular label moiety can be used for detection. Exemplary detection methods include, but are not limited to, spectroscopic, fluorescent, photochemical, biochemical, immunochemical, electrical, optical or chemical methods. In some embodiments of any of the aspects, measuring can be a quantitative observation. 
     As used herein, the terms “treat,” “treatment,” “treating,” or “amelioration” refer to therapeutic treatments, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a condition associated with a disease or disorder, e.g. bronchial premalignant lesion. The term “treating” includes reducing or alleviating at least one adverse effect or symptom of a condition, disease or disorder associated with a bronchial premalignant lesion. Treatment is generally “effective” if one or more symptoms or clinical markers are reduced. Alternatively, treatment is “effective” if the progression of a disease is reduced or halted. That is, “treatment” includes not just the improvement of symptoms or markers, but also a cessation of, or at least slowing of, progress or worsening of symptoms compared to what would be expected in the absence of treatment. Beneficial or desired clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, remission (whether partial or total), and/or decreased mortality, whether detectable or undetectable. The term “treatment” of a disease also includes providing relief from the symptoms or side-effects of the disease (including palliative treatment). 
     As used herein, the term “pharmaceutical composition” refers to the active agent in combination with a pharmaceutically acceptable carrier e.g. a carrier commonly used in the pharmaceutical industry. The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. In some embodiments of any of the aspects, a pharmaceutically acceptable carrier can be a carrier other than water. In some embodiments of any of the aspects, a pharmaceutically acceptable carrier can be a cream, emulsion, gel, liposome, nanoparticle, and/or ointment. In some embodiments of any of the aspects, a pharmaceutically acceptable carrier can be an artificial or engineered carrier, e.g., a carrier that the active ingredient would not be found to occur in in nature. 
     As used herein, the term “administering,” refers to the placement of a compound as disclosed herein into a subject by a method or route which results in at least partial delivery of the agent at a desired site. Pharmaceutical compositions comprising the compounds disclosed herein can be administered by any appropriate route which results in an effective treatment in the subject. In some embodiments, administration comprises physical human activity, e.g., an injection, act of ingestion, an act of application, and/or manipulation of a delivery device or machine. Such activity can be performed, e.g., by a medical professional and/or the subject being treated. 
     As used herein, “contacting” refers to any suitable means for delivering, or exposing, an agent to at least one cell. Exemplary delivery methods include, but are not limited to, direct delivery to cell culture medium, perfusion, injection, or other delivery method well known to one skilled in the art. In some embodiments, contacting comprises physical human activity, e.g., an injection; an act of dispensing, mixing, and/or decanting; and/or manipulation of a delivery device or machine. 
     As used herein, the term “inhibitor” refers to an agent which can decrease the expression and/or activity of the target molecule or activity or process, e.g. by at least 10% or more, e.g. by 10% or more, 50% or more, 70% or more, 80% or more, 90% or more, 95% or more, or 98% or more. 
     As used herein, the terms “drug”, “compound” or “agent” are used interchangeably and refer to molecules and/or compositions. The compounds/agents include, but are not limited to, chemical compounds and mixtures of chemical compounds, e.g., small organic or inorganic molecules; saccharines; oligosaccharides; polysaccharides; biological macromolecules, e.g., peptides, proteins, and peptide analogs and derivatives; peptidomimetics; nucleic acids; nucleic acid analogs and derivatives; extracts made from biological materials such as bacteria, plants, fungi, or animal cells or tissues; naturally occurring or synthetic compositions; peptides; aptamers; and antibodies and intrabodies, or fragments thereof. In some embodiments, “drug” as used herein refers to an agent approved for medical use, e.g., by the FDA. 
     The term “statistically significant” or “significantly” refers to statistical significance and generally means a two standard deviation (2SD) or greater difference. 
     Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term “about.” The term “about” when used in connection with percentages can mean±1%. 
     As used herein, the term “comprising” means that other elements can also be present in addition to the defined elements presented. The use of “comprising” indicates inclusion rather than limitation. 
     The term “consisting of” refers to compositions, methods, and respective components thereof as described herein, which are exclusive of any element not recited in that description of the embodiment. 
     As used herein the term “consisting essentially of” refers to those elements required for a given embodiment. The term permits the presence of additional elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment of the invention. 
     The singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise. Similarly, the word “or” is intended to include “and” unless the context clearly indicates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below. The abbreviation, “e.g.” is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example. Thus, the abbreviation “e.g.” is synonymous with the term “for example.” 
     Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims. 
     Unless otherwise defined herein, scientific and technical terms used in connection with the present application shall have the meanings that are commonly understood by those of ordinary skill in the art to which this disclosure belongs. It should be understood that this invention is not limited to the particular methodology, protocols, and reagents, etc., described herein and as such can vary. The terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention, which is defined solely by the claims. Definitions of common terms in immunology and molecular biology can be found in The Merck Manual of Diagnosis and Therapy, 20th Edition, published by Merck Sharp &amp; Dohme Corp., 2018 (ISBN 0911910190, 978-0911910421); Robert S. Porter et al. (eds.), The Encyclopedia of Molecular Cell Biology and Molecular Medicine, published by Blackwell Science Ltd., 1999-2012 (ISBN 9783527600908); and Robert A. Meyers (ed.), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8); Immunology by Werner Luttmann, published by Elsevier, 2006; Janeway&#39;s Immunobiology, Kenneth Murphy, Allan Mowat, Casey Weaver (eds.), W. W. Norton &amp; Company, 2016 (ISBN 0815345054, 978-0815345053); Lewin&#39;s Genes XI, published by Jones &amp; Bartlett Publishers, 2014 (ISBN-1449659055); Michael Richard Green and Joseph Sambrook, Molecular Cloning: A Laboratory Manual, 4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., USA (2012) (ISBN 1936113414); Davis et al., Basic Methods in Molecular Biology, Elsevier Science Publishing, Inc., New York, USA (2012) (ISBN 044460149X); Laboratory Methods in Enzymology: DNA, Jon Lorsch (ed.) Elsevier, 2013 (ISBN 0124199542); Current Protocols in Molecular Biology (CPMB), Frederick M. Ausubel (ed.), John Wiley and Sons, 2014 (ISBN 047150338X, 9780471503385), Current Protocols in Protein Science (CPPS), John E. Coligan (ed.), John Wiley and Sons, Inc., 2005; and Current Protocols in Immunology (CPI) (John E. Coligan, ADA M Kruisbeek, David H Margulies, Ethan M Shevach, Warren Strobe, (eds.) John Wiley and Sons, Inc., 2003 (ISBN 0471142735, 9780471142737), the contents of which are all incorporated by reference herein in their entireties. 
     Other terms are defined herein within the description of the various aspects of the invention. 
     All patents and other publications; including literature references, issued patents, published patent applications, and co-pending patent applications; cited throughout this application are expressly incorporated herein by reference for the purpose of describing and disclosing, for example, the methodologies described in such publications that might be used in connection with the technology described herein. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing in this regard should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents. 
     The description of embodiments of the disclosure is not intended to be exhaustive or to limit the disclosure to the precise form disclosed. While specific embodiments of, and examples for, the disclosure are described herein for illustrative purposes, various equivalent modifications are possible within the scope of the disclosure, as those skilled in the relevant art will recognize. For example, while method steps or functions are presented in a given order, alternative embodiments may perform functions in a different order, or functions may be performed substantially concurrently. The teachings of the disclosure provided herein can be applied to other procedures or methods as appropriate. The various embodiments described herein can be combined to provide further embodiments. Aspects of the disclosure can be modified, if necessary, to employ the compositions, functions and concepts of the above references and application to provide yet further embodiments of the disclosure. These and other changes can be made to the disclosure in light of the detailed description. All such modifications are intended to be included within the scope of the appended claims. 
     Specific elements of any of the foregoing embodiments can be combined or substituted for elements in other embodiments. Furthermore, while advantages associated with certain embodiments of the disclosure have been described in the context of these embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the disclosure. 
     The technology described herein is further illustrated by the following examples which in no way should be construed as being further limiting. 
     Some embodiments of the technology described herein can be defined according to any of the following numbered paragraphs:
         1. A method of treating bronchial premalignant lesions, the method comprising:
           administering at least one of:
               i. both a bronchoscopy-based procedure to survey the central airway and a chest CT scan;   ii. at least every 6 months, one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or   iii. at least one anti-proliferative drug;   
               to a subject determined to have at least one of:   an increased level of expression of at least one module 5 gene as compared to a non-proliferative lesion reference level; and   a decreased level of expression of at least one module 6 gene as compared to a non-proliferative lesion reference level.   
           2. The method of paragraph 1, wherein the at least one module 5 gene is selected from the group consisting of:
           RACGAP1 and TPX2; and   
           the at least one module 6 gene is selected from the group consisting of:
           NEK11 and IFT88.   
           3. The method of any of paragraphs 1-2, wherein the subject is further determined to have an increased level of expression of at least one module 7 or module 4 gene.   4. The method of paragraph 3, wherein the at least one module 7 or module 4 gene is selected from the group consisting of:
           COX6A1; COX7A2; RPL26; and RPL23.   
           5. The method of any of paragraphs 1-4, wherein the level of expression of each of the genes of Table 15 is determined.   6. The method of any of paragraphs 1-5, wherein the at least one anti-proliferative drug is selected from the group consisting of:
           Acetylcholine receptor antagonist; Acetylcholinesterase inhibitors; Adenosine receptor antagonists; Adrenergic receptor antagonists; AKT inhibitors; Angiotensin receptor antagonists; Apoptosis stimulants; Aurora kinase inhibitors; CDK inhibitors; Cyclooxygenase inhibitors; Cytokine production inhibitors; Dehydrogenase inhibitors; DNA protein kinase inhibitors; focal adhesion inhibitors; Dopamine receptor antagonist; EGFR inhibitors; ERK1 and ERK2 phosphorylation inhibitors; Estrogen receptor agonists; EZH2 inhibitors; FLT3 inhibitors; Glucocorticoid receptor agonists; Glutamate receptor antagonists; HDAC inhibitors; Histamine receptor antagonists; Histone lysine methyltransferase inhibitors; HSP inhibitors; IKK inhibitors; Ion channel antagonists; JAK inhibitors; JNK inhibitors; KIT inhibitors; Leucine rich repeat kinase inhibitors; MDM inhibitors; mediator release inhibitors; MEK inhibitors; MTOR inhibitors; Monoamine oxidase inhibitors; NFkB pathway inhibitors; nucleophosmin inhibitors; PARP inhibitors; PPAR receptor agonists; PI3K inhibitors; tyrosine kinase inhibitors; Phosphodiesterase inhibitors; protein kinase inhibitors; RAF inhibitors; RNA polymerase inhibitors; topoisomerase inhibitors; RNA synthesis inhibitors; SIRT inhibitors; sodium channel blockers; VEGFR inhibitors; and Vitamin D receptor agonists.   
           7. The method of any of paragraphs 1-6, wherein the anti-proliferative drug is administered as an inhaled formulation or topical formulation.   8. The method of any of paragraphs 1-7, wherein the anti-proliferative drug is administered during a bronchoscopy-based procedure.   9. The method of any of paragraphs 1-8, wherein the anti-proliferative drug is administered systemically.   10. The method of any of paragraphs 1-9, wherein the anti-proliferative drug is administered during a bronchoscopy-based procedure and systemically.   11. The method of any of paragraphs 1-10, wherein the subject is further determined to have a decreased level of expression of at least one module 9 gene as compared to a non-proliferative lesion reference level and/or an increased level of expression of at least one module 10 gene as compared to a non-proliferative lesion reference level.   12. The method of paragraph 11, wherein the subject determined to have a decreased level of expression of at least one module 9 gene and/or an increased level of expression of at least one module 10 gene is administered at least one of:
           i. both a bronchoscopy-based procedure to survey the central airway wherein the lesions are biopsied to remove abnormal tissue and a chest CT scan;   ii. at least every 6 months, one of a bronchoscopy-based procedure to survey the central airway wherein the lesions are biopsied to remove abnormal tissue and a chest CT scan; and/or   iii. at least one immune stimulating drug.   
           13. A method of treating bronchial premalignant lesions, the method comprising:
           administering at least one of:
               i. both a bronchoscopy-based procedure to survey the central airway wherein the lesions are biopsied to remove abnormal tissue and a chest CT scan;   ii. at least every 6 months, one of a bronchoscopy-based procedure to survey the central airway wherein the lesions are biopsied to remove abnormal tissue and a chest CT scan; and/or iii. at least one immune stimulating drug;   to a subject determined to have a decreased level of expression of at least one module 9   
               gene as compared to a non-proliferative lesion reference level and/or an increased level of expression of at least one module 10 gene as compared to a non-proliferative lesion reference level.   
           14. The method of any of paragraphs 11-13, wherein the module 9 gene is selected from the group consisting of:
           EPSTI1; UBE2L6; B2M and TAP1.   
           15. The method of any of paragraphs 11-14, wherein the at least one gene module 9 gene is selected from Table 16.   16. The method of any of paragraphs 11-15, wherein the module 10 gene is selected from the group consisting of:
           CACNB3 and MAPK10.   
           17. The method of any of paragraphs 11-16, wherein the at least one immune stimulating drug is selected from the group consisting of:
           immune-checkpoint inhibitors (e.g. inhibitors against, PD-1, PD-L1, CTLA4, and LAG3); drugs that stimulate interferon signaling (e.g. anti-viral drugs that improve interferon signaling); DNA synthesis inhibitors; IMDH inhibitors; CDK inhibitors; ribonucleotide reductase inhibitors; dihydrofolate reductase inhibitors; topoisomerase inhibitors; FLT3 inhibitors; IGF-1 inhibitors; MEK inhibitors; aurora kinase inhibitors; PKC inhibitors; RAF inhibitors; PDFGR/KIT inhibitors; VEGFR inhibitors; SRC inhibitors; retinoid receptor agonists; HDAC inhibitors; DNA methyltransferase inhibitors; and EZH2 inhibitors.   
           18. A method of treating bronchial premalignant lesions, the method comprising:
           administering at least one of:
               i. both a bronchoscopy-based procedure to survey the central airway and a chest CT scan;   ii. at least every 6 months, one of a bronchoscopy-based procedure to survey the central airway and a chest CT scan; and/or   iii. at least one anti-inflammatory drug;   
               to a subject determined to have at least one of:   an increased level of expression of at least one module 2 gene as compared to a non-inflammatory reference level; and   a decreased level of expression of at least one module 6 gene as compared to a non-inflammatory reference level.   
           19. The method of paragraph 17, wherein the at least one module 2 gene is selected from the group consisting of:
           MSANTD2, CCNL2, and LUC7L; and   the at least one module 6 gene is selected from the group consisting of:   NEK11 and IFT88.   
           20. The method of any of paragraphs 17-18, wherein the subject is further determined to have an increased level of expression of at least one module 7 gene, module 1 gene, or module 8 gene and/or decreased level of expression of at least one module 4 gene or one module 5 gene.   21. The method of paragraph 19, wherein the at least one module 7 gene is selected from the group consisting of: RPL26 and RPL23.   22. The method of paragraph 19, wherein the at least one module 1 gene is selected from the group consisting of: KIRREL; PHLDB1; and MARVELD1.   23. The method of paragraph 19, wherein the at least one module 8 gene is selected from the group consisting of: DOC2; CD53; and LAP™.   24. The method of paragraph 19, wherein the at least one module 4 gene is selected from the group consisting of: COX6A1 and COX7A2   25. The method of paragraph 19, wherein the at least one module 5 gene is selected from the group consisting of: RACGAP1 and TPX2   26. The method of any of paragraphs 17-24, wherein the level of expression of each of the genes of Table 15 is determined.   27. The method of any of paragraphs 17-25, wherein the at least one anti-inflammatory drug is selected from the group consisting of:
           Acetylcholine receptor antagonists; Acetylcholinesterase inhibitors; Adenosine receptor antagonists; Adrenergic receptor antagonists; Angiotensin receptor antagonists; Anti-IL1B antibodies; Apoptosis stimulants; Aurora kinase inhibitors; CDK inhibitors; Cyclooxygenase inhibitors; Cytokine production inhibitors; Dehydrogenase inhibitors; Dopamine receptor antagonists; EGFR inhibitors; ERK1 and ERK2 phosphorylation inhibitors; Estrogen receptor agonists; FLT3 inhibitors; Glucocorticoid receptor agonists; Glutamate receptor antagonists; HDAC inhibitors; Histamine receptor antagonists; Histone lysine methyltransferase inhibitors; HSP inhibitors; IKK inhibitors; Ion channel antagonists; KIT inhibitors; Leucine rich repeat kinase inhibitors; MEK inhibitors; MDM inhibitors; Phosphodiesterase inhibitors; Monoamine oxidase inhibitors; MTOR inhibitors; NFkB pathway inhibitors; nucleophosmin inhibitors; PARP inhibitors; PI3K inhibitors; PPAR receptor agonists; protein synthesis inhibitors (e.g. chloramphenicol); RAF inhibitors; SIRT inhibitors; Sodium channel blockers; TGF beta receptor inhibitors; Topoisomerase inhibitors; Tyrosine kinase inhibitors; VEGFR inhibitors; and Vitamin D receptor agonists.   
           28. The method of any of paragraphs 17-26, wherein the anti-inflammatory drug is administered during a bronchoscopy-based procedure.   29. The method of any of paragraphs 17-27, wherein the anti-inflammatory drug is administered systemically.   30. The method of any of paragraphs 17-28, wherein the anti-inflammatory drug is administered during a bronchoscopy-based procedure and systemically.   31. The method of any of paragraphs 1-29, wherein the at least one gene is selected from Table 14.   32. The method of any of paragraphs 1-30, wherein the level of expression of each of the genes of Table 14 is determined.   33. The method of any of paragraphs 1-31, whereby the development of lung cancer lung squamous cell carcinoma is prevented, delayed, or slowed.   34. The method of any of paragraphs 1-32, wherein the lung cancer is lung squamous cell carcinoma.   35. The method of any of paragraphs 1-33, wherein the level of expression is the level of expression in an endobronchial biopsy, endobronchial brushing sample, large airway biopsy, large airway brushing sample, nasal epithelial cells, sputum, or blood obtained from the subject.   36. The method of any of paragraphs 1-34, wherein the level of expression is the level of expression in a bronchial brushing obtained from the right or left mainstem bronchus.   37. The method of any of paragraphs 34-35, wherein the biopsy or brushing sample comprises morphologically-normal tissues or cells.   38. The method of any of paragraphs 34-35, wherein the biopsy or brushing sample consists of morphologically-normal tissues or cells.   39. The method of any of paragraphs 1-34, wherein the level of expression is the level of expression in a sample comprising bronchial premalignant lesion cells.   40. The method of any of paragraphs 1-35, wherein the level of expression is the level of expression in a sample comprising morphologically-normal cells.   41. The method of any of the paragraphs 1-36, wherein the subject is a smoker or former smoker.       

     EXAMPLES 
     Example 1: Molecular Subtyping Reveals Immune Alterations Associated with Progression of Bronchial Premalignant Lesions 
     Described herein is the molecular characterization of bronchial premalignant lesions and the airway field of injury identified epithelial and immune alterations associated with progressive/persistent bronchial dysplasia that can be leveraged to develop lung cancer risk biomarkers and interception strategies. 
     Bronchial premalignant lesions (PMLs) are precursors of lung squamous cell carcinoma, but have variable outcome, and tools are lacking to identify and treat PMLs at highest risk for progression to invasive cancer. Profiling endobronchial biopsies of PMLs obtained from high-risk smokers by RNA-Seq identified four PML subtypes with differences in epithelial and immune processes. One molecular subtype (Proliferative) is enriched with dysplastic lesions and exhibits up-regulation of metabolic and cell cycle pathways and down-regulation of ciliary processes. RNA-Seq profiles from normal-appearing uninvolved large airway brushings could identify subjects with Proliferative lesions with high specificity. Expression of interferon signaling and antigen processing/presentation pathways are decreased in progressive/persistent Proliferative lesions and immunofluorescence indicates a depletion of innate and adaptive immune cells in these lesions. Molecular biomarkers measured in PMLs or the uninvolved airway can enhance histopathological grading and indicates that immunoprevention strategies may be effective in intercepting the progression of PMLs to lung cancer. 
     Introduction 
     Lung cancer (LC) is the leading cause of cancer death taking about 160,000 U.S. lives each year, more than colorectal, pancreatic, breast, and prostate cancers combined. In order to decrease mortality, innovative strategies are needed to intercept cancer development by diagnosing the disease at its earliest and potentially most curable stage. Recent advances based on results from the National Lung Screening Trial (1) are dramatically altering the landscape of early LC detection as computed tomography (CT) screening of high-risk individuals significantly reduces mortality. Despite this progress, biomarkers are needed to select individuals for LC screening as eligibility criteria account for less than 27% of individuals diagnosed with LC in the US (2) and to distinguish between benign or cancerous indeterminate pulmonary nodules as screening has very high false positive rate (&gt;90%). There is also urgent and unmet need to develop personalized therapies earlier in the disease process to “intercept” LC prior to its development in this high-risk population. 
     Development of LC risk biomarkers and LC interception strategies requires a detailed understanding of the earliest molecular alterations involved in lung carcinogenesis that occur in the respiratory epithelium (3, 4). Exposure to cigarette smoke creates a field of injury throughout the entire respiratory tract by inducing a variety of genomic alterations that can lead to an “at-risk” airway where premalignant lesions (PMLs) and LCs develop. Lung squamous cell carcinoma (LUSC) arises in the epithelial layer of the bronchial airways and is often preceded by the development of PMLs through a stepwise histological progression from normal epithelium to hyperplasia, squamous metaplasia, dysplasia (mild, moderate and severe), carcinoma in situ (CIS), and finally to invasive and then metastatic LUSC (5). In fact, the presence of high-grade persistent or progressive dysplasia (moderate or severe) is a marker of increased LC risk both at the lesion site (where they are the presumed precursors of squamous cell lung cancer) and elsewhere in the lung, although many dysplastic lesions do have varied outcomes (6). Currently, however, effective tools to identify PMLs are lacking at highest risk of progression to invasive carcinoma (7). The development of markers of disease progression would identify patients at high-risk, suggest novel lung cancer chemoprevention agents, and provide molecular biomarkers for monitoring outcome in lung cancer prevention trials. 
     It is hypothesized herein that molecular characterization of bronchial biopsies containing a mixture of epithelial and immune cells would allow us to identify transcriptomic alterations associated with high-grade histology and premalignant lesion progression. In this study, mRNA sequencing was used to profile endobronchial biopsies and brushings obtained through serial bronchoscopies from high-risk smokers undergoing lung cancer screening by auto-fluorescence bronchoscopy and chest CT. Using the bronchial biopsies, four molecular subtypes associated with clinical phenotypes and biological processes were identified. One subtype (Proliferative subtype) is enriched with biopsies having dysplastic histology, high basal cell and low ciliated cell signals, and expression of proliferation-associated pathways. Genes involved in interferon signaling and T cell mediated immunity were down-regulated among progressive/persistent lesions within the Proliferative subtype compared with regressive lesions and these pathways correlated with decreases in both innate and adaptive immune cell types. Molecular classification of biopsies into a high-grade/progressive disease group can be used to stratify patients into prevention trials and to monitor efficacy of the treatment. The results also indicate that personalized lung cancer chemoprevention targeting specific cancer-related pathways or the immune system can have potential therapeutic benefits. 
     Results 
     Subject Population 
     In this study, mRNA sequencing was used to profile endobronchial biopsies and brushings obtained through serial bronchoscopy of high-risk smokers undergoing lung cancer screening by auto-fluorescence bronchoscopy and chest CT at the Roswell Park Comprehensive Cancer Center (Roswell) in Buffalo, N.Y. The Discovery Cohort samples were obtained from the Roswell subjects between 2010 and 2012 (DC; n=29 patients, n=191 biopsies, n=91 brushes), and the Validation Cohort samples were obtained between 2012 and 2015 (VC; n=20 patients, n=111 biopsies, and 49 brushes). The subjects are predominantly older smokers, many of which have a history of lung cancer, chronic obstructive pulmonary disease (COPD), and occupational exposures that confer a high-risk of developing lung cancer. Clinical characteristics reported at baseline such as sex, age, smoking status (ever or never) reported at baseline visit, pack-years, prior history of lung cancer, COPD status, and occupational exposures were not significantly different between the two cohorts (Table 1). After sample filtering based on several quality metrics, the DC had 190 biopsies and 89 brushes while the VC had 105 biopsies and 48 brushes. Ninety-four percent of subjects had at least one lung anatomic location sampled 2 or more times via endobronchial biopsy. The DC and VC contained 37.9% and 35.2% biopsies with a histological grade of dysplasia or higher and 23.1% and 19.0% had progressive/persistent dysplasia, respectively (Table 2). A previously described smoking-associated signature (8) was used to predict the smoking status of each sample, as smoking status was only available at baseline, and found that the DC had a higher percentage of biopsies predicted to be current smokers (62.6%) compared with the VC (36.2%). There is no significant difference in smoking status among the bronchial brushings between the two cohorts since only 1 brush is collected per time point. The predicted smoking status was consistent across all procedures for 63% and 70% of the DC and VC subjects, respectively. In terms of RNA sequencing quality, the DC had significantly greater total reads, percent uniquely mapping reads, and median transcript integrity number scores among the biopsies than the VC, but these differences between cohorts were not reflected in the brushes ( FIG.  5   ). 
     LUSC PMLs within the Discovery Cohort Divide into Distinct Molecular Subtypes 
     In order to identify gene expression differences associated with LUSC PML histological severity using the endobronchial biopsies, a discovery-based approach was used to identify de novo molecular subtypes based on distinct patterns of gene co-expression (gene modules). The approach was chosen given that there is histological heterogeneity within biopsies and that pathological analyses were conducted using biopsies adjacent to biopsies profiled via mRNA-Seq. First, it was sought to select a set of gene modules that are present across different LUSC datasets. Using weighted gene co-expression network analysis (9) (WGCNA), gene modules were derived in the DC biopsies (n=190 samples, n=16653 genes, n=15 gene modules), the DC brushes (n=89 samples, n=16058 genes, n=47 gene modules), TCGA squamous cell carcinoma (LUSC) tumors (10) (n=471 samples, n=17887 genes, n=55 gene modules), and tracheobronchial samples from mice treated with n-nitrosotris-(2-choroethyl)urea (NTCU) (n=25 samples, n=14897 genes, n=40 gene modules). DC biopsy gene modules that were highly correlated (absolute Pearson correlation coefficient r&gt;0.85) to at least one other non-DC biopsy module within each of the 4 datasets were selected. Genes in the selected modules were filtered by requiring that each gene was also present in at least one of the correlated non-DC biopsy modules, resulting in a set of 9 gene modules that consisted of 3,936 genes in total ( FIG.  6   ). These gene modules identified 4 molecular subtypes within the DC biopsies via consensus clustering: Proliferative (dark blue, n=52 samples, 27.4%), Inflammatory (dark green, n=37 samples, 19.5%), Secretory (light blue, n=61 samples, 32.1%), and Normal-like (light green, n=40 samples, 21.1%) ( FIG.  1 A , Table 3). 
     In order to characterize each molecular subtype, the first focus was on identifying biological pathways over-represented in the genes comprising each gene module, as the pattern of gene module expression defines each PML subtype. Each gene module was found to be associated with distinct epithelial and immune biological processes ( FIG.  1 A ,  FIG.  6   , and Table 5). The Proliferative subtype is specifically characterized by increased expression of genes involved in energy metabolism and cell cycle pathways (Modules 4 and 5). The Secretory and Normal-like subtypes both have increased expression of genes in cilium-associated pathways (Module 6), however, the Normal-like subtype specifically has decreased expression of genes involved in inflammation, regulation of lymphocytes and leukocytes, and antigen processing and presentation pathways (Modules 8 and 9). The Secretory subtype exhibits decreased expression of genes involved in protein translation (Module 7), while RNA processing genes (Module 2) are expressed more highly in the Inflammatory subtype. 
     The molecular subtypes were further characterized by their associations with clinical phenotypes and established LUSC tumor molecular subtypes (11, 12). Sample smoking status, the subject from whom the sample was derived, and sample histology demonstrated significant associations with subtype (p&lt;0.01,  FIG.  1 B , Table 6,  FIG.  8   ). The Proliferative and Secretory subtypes are enriched for current smokers and this association drives the subject enrichment as 79% of subjects maintain their smoking status throughout the study. Additionally, the Proliferative subtype is enriched for biopsies with dysplasia histology ( FIG.  1 B ). The Proliferative subtype has high expression of genes involved in cell cycle processes including the proliferation marker MKI67, which is significantly up-regulated among samples in this subtype compared with samples in other subtypes (FDR=1.0e-30, linear model, based on differential expression analysis between samples in the Proliferative versus the non-Proliferative subtypes across all genes). The gene remained significantly up-regulated in the Proliferative subtype within samples with normal/hyperplasia histology (FDR=3.4e-10, linear model) and samples with dysplasia histology (FDR=3.1e-8, linear model), and these observations are supported by an increase in protein expression in representative samples (p=0.02) ( FIG.  1 C- 1 E  and  FIG.  9   ). The Proliferative subtype samples also had high concordance with the LUSC-Classical subtype ( FIG.  1 B ). In the TCGA LUSC tumors, the LUSC-Classical subtype was associated with alterations and overexpression of KEAP1 and NFE2L2 as well as amplification of 3q26 with overexpression of SOX2, TP63 and PIK3CA (11). Similarly, our Proliferative PMLs have increased expression of KEAP1, NFE2L2, TP63, and PIK3CA (FDR=1.4e-6, 4.5e-12, 1.4e-9, and 0.03, respectively, linear model) ( FIG.  10 A ). Furthermore, the LUSC-Classical subtype was found to be associated with increased expression of genes involved in energy metabolism, and our Proliferative subtype is in part defined by high expression of Module 4, which is enriched for genes associated with oxidative phosphorylation and the electron transport chain. In contrast, the Inflammatory and Secretory PML subtypes demonstrate enrichment for the LUSC-Secretory subtype. The LUSC-Secretory subtype was associated with processes related to the immune response, and the Inflammatory and Secretory PMLs have the highest expression of Module 8 that is enriched for genes in these same pathways. 
     Finally, the extent to which the PML molecular subtypes were driven by differences in epithelial and immune cell type composition by assessing expression of a number of canonical cell type markers was examined. The Inflammatory and Secretory subtypes have higher levels of expression of the white blood cell marker PTPRC (CD45) consistent with enrichment of the LUSC-Secretory subtype (FIG.  10 B, FDR=0.12 and 0.01, respectively, linear model). Consistent with the behavior and pathways enriched in Module 6, the ciliated cell marker TUB1A1 expression is decreased in the Inflammatory and Proliferative subtypes (FDR=1.1e-4 and 3.5e-19, respectively, linear model), and this is also shown by a decrease in acetylated a-tubulin staining in representative histological samples ( FIG.  1 E ,  FIG.  9   ). The Proliferative subtype has the highest expression (FDR=2.4e-15.1 linear model) of basal cell marker (KRT5) indicating enrichment of lesions with high-grade histology that tightly correlates with protein expression in representative histology samples (p=0.01) ( FIG.  1 E ,  FIG.  9   ,  FIG.  10 B , Table 7). Additionally, gene expression of MUC5AC, a marker of goblet epithelial cells, is increased in subtypes enriched for current smokers (Proliferative and Secretory) but is the most significantly increased in the Secretory subtype (FDR=3.4e-5, linear model). In contrast, gene expression of SCGB1A1, a marker of club cells, is the lowest in the Proliferative subtype (FDR=6.1e-5, linear model). The Normal-like subtype is supported by expression of all epithelial cell types and has the lowest expression of CD45 (FDR=7.6e-4, linear model). The expression levels of these marker genes agree with cell type deconvolution methods to examine epithelial and immune cell content ( FIG.  10 C- 10 D ). The summation of these characterizations highlights epithelial and immune cell associated pathways that are modulated by smoking and PML histology and identifies the Proliferative subtype as a subset of high-grade PMLs that express proliferative and cell cycle-related pathways. 
     Phenotypic Associations with the Molecular Subtypes are Confirmed in the Validation Cohort 
     Next, it was desired to determine if the heterogeneity captured in the DC biopsy-derived molecular subtypes was reproducible in the VC. A 22-gene nearest centroid molecular subtype predictor was developed by selecting genes representative of each of the 9 gene modules. The predictor has 84.7% accuracy across DC biopsies (training set,  FIG.  2 A  and  FIG.  11   ) with the following misclassification rates per subtype 5/52 (9.6%) in Proliferative, 7/37 (18.9%) in Inflammatory, 9/61 (14.8%) in Secretory, and 8/40 (20%) in Normal-like. The 22-gene classifier was used to predict the molecular subtype of the 105 VC biopsies ( FIG.  2 B ). The VC subtype predictions were evaluated by examining the concordance of metagene scores for each of the 9 modules (using the full set of genes for each module) between the predicted VC subtypes compared with the DC subtypes. The average behavior of Principal Component 1 (PC1) across the subtypes was highly similar ( FIG.  12   ) with few exceptions (namely, Module 3 that had the fewest genes). Additionally, the VC subtype predictions from the 22-gene classifier were compared to subtypes derived in the VC biopsies using the same methodology used to derive the DC subtypes and found significant concordance (p=1.0e-7, with the Proliferative subtype having the greatest concordance between predictions,  FIG.  11   ). 
     The statistical associations between the VC subtypes (via the 22-gene classifier) and clinical and molecular phenotypes across the VC biopsies are analogous to those observed across the DC biopsies ( FIG.  2 C , Table 6,  FIG.  8    and  FIG.  10 A- 10 H ). Briefly, the Proliferative subtype is enriched for current smokers, biopsies with dysplasia histology, and the LUSC-Classical tumor subtype ( FIG.  2 C , Table 6). Epithelial and white blood cell marker gene expression across the VC biopsies reveals higher levels of the white blood cell marker PTPRC (CD45 expression) in the Inflammatory subtype (FDR=0.002) consistent with enrichment of the LUSC-Secretory subtype ( FIG.  10 F ). 
     The Inflammatory and Proliferative subtypes have reduced ciliated cell marker expression (FOXJ1) consistent with Module 6 (FOXJ1 FDR=0.0005 and FDR=2.62e-6 and Module 6 FDR=5.73e-6 and FDR=4.34e-10, respectively). The Proliferative subtype has the highest expression of basal cell marker KRT5 (FDR=1.67e-7), proliferation marker MK167 (FDR=3.03e-10), and cell cycle associated Module 5 (FDR=1.23e-18) indicating enrichment of lesions expressing characteristics associated with high-grade histology. Gene expression of SCGB1A1, a marker of club cells, is the lowest in the Proliferative subtype (FDR=1.8e-4). Gene expression of MUC5AC, a marker of goblet epithelial cells, was increased in current smokers and most significantly in the Secretory subtype in the DC biopsies; however, in the VC biopsies this trend is not preserved as current smokers are not enriched in the Secretory subtype. The expression levels of these marker genes agree with other deconvolution methods to examine epithelial and immune cell content ( FIG.  10 E- 10 H ). 
     Normal Appearing Airway Field Brushes Reflect Biopsy Molecular Subtype 
     Previously, it was shown that bronchial brushes from normal appearing areas of the mainstem bronchus could predict the presence of PMLs (13); however, that study lacked biopsies and brushes from the same subjects. Above, in both the DC and the VC biopsies, the Proliferative subtype, represents a distinct subtype of PMLs enriched for dysplastic histology expressing metabolic and proliferative pathways. Biopsies classified as the Proliferative subtype may represent a group of PMLs that need close monitoring and intervention. As a result, it was sought to explore whether or not it was possible to predict the presence of Proliferative subtype biopsies using the brushes. The Proliferative subtype is defined by the behavior of Modules 4, 5, 6, and 7 (Table 3), and therefore, the subset of 8 genes (from the 22-gene predictor) that correspond to these Modules was used to predict the presence of the Proliferative subtype across the DC and VC biopsies and brushes. A prediction of the Proliferative subtype in a brush is specific (91% and 92% in the DC and VC biopsies, respectively), but not sensitive (39% and 32% DC and VC biopsies, respectively) at indicating the presence of at least one Proliferative PML detected at the same time point ( FIG.  3 A ). In order to understand the classifier&#39;s performance in predicting the Proliferative subtype in brushes, Gene Set Variation Analysis (GSVA)(14) scores were examined for Modules 4, 5, 6, and 7 that define the Proliferative subtype in the DC and VC brushes ( FIG.  3 B ). In the DC and VC brushes, the GSVA scores were significantly different (FDR&lt;0.05) in the Proliferative subtype versus all other samples only for Modules 5 and 6, and thus these likely contribute the most heavily to Proliferative subtype classification in the brushes. Module 5 contains genes associated with cell cycle and proliferation while Module 6 contains genes associated with cilium assembly and organization. Down-regulation of Modules 5 and 6 in the brushes specifically predicts the presence of a Proliferative subtype PML; however, the absence of these signals in the airway field of injury does not preclude the development of a Proliferative subtype PML. 
     Immune-associated genes separate proliferative subtype progressive/persistent and regressive PMLs. Previous studies of bronchial PMLs suggest that high-grade lesions (which occur more frequently in current smokers) are more likely to progress to invasive carcinoma (6). Therefore, it was sought to identify molecular alterations associated with subsequent PML progression/persistence (n=15) versus regression (n=15) among the Proliferative subtype DC biopsies, as these may be clinically relevant to identifying appropriate interception strategies. Using GSVA scores calculated across all the DC biopsies for each of the 9 modules, it was calculated which scores were statistically different between progressive/persistent versus regressive disease in the samples belonging to the Proliferative subtype ( FIG.  7   ). It was found that the DC biopsy GSVA Module scores for Module 9 were significantly higher among regressive Proliferative PMLs (p=0.002, linear model  FIG.  4 A ) compared with progressive/persistent Proliferative PMLs. The association between low Module 9 score and progression/persistence is replicated in the VC biopsies (n=7 progressive/persistent and n=13 regressive biopsies; p=0.03, linear model  FIG.  4 B ). The ability of the Module 9 GSVA scores to discriminate between regressive versus progressing/persistent biopsies as measured by the area under the receiver operating characteristic (ROC) was 0.809 and 0.802 in the DC and VC biopsies, respectively. 
     The genes in Module 9 include a number of genes that encode for proteins involved in interferon signaling as well as antigen processing and presentation (SP100, CIITA, CXCL10, SOCS1, GBP1, GBP4, B2M, TAP1, TAPBP, TRIM 14, TRIM21, TRIM122, STAT1, PML, OAS2, OAS3, MX1, ADAR, ISG15, IFI35, IFIT3, IFI27, PSMB8, PSMB9, BST2, IRF1, IRF9, CD74, PSME1, PSME2, HLA-DQA1/DPA1/DPB1/DRA/DQB2/DRB1/DQB1/DMA/DMB/D0A, HLA-A/B/C/E/F) and include the inhibitory receptor LAGS. As a result, it was wanted to evaluate whether or not the presence or absence of innate or adaptive immune cells were associated with Module 9 expression within the Proliferative subtype. In an effort to deconvolute the potential presence of immune cell types, GSVA scores were generated using previously described immune cell signatures (15) and scores for 64 different cell types using the xCell algorithm (16), separately for both the DC and VC biopsies. Significant (FDR&lt;0.05) associations were identified between the cell type scores and Module 9 that were in common between the DC and VC biopsies ( FIG.  13   ) and 8 cell types identified (via xCell) including dendritic cells, activated dendritic cells, plasmacytoid dendritic cells, macrophages, M1 macrophages as well as CD8+ effector memory T cells, CD8+ central memory T cells, and T regulatory cells ( FIG.  4 C ). Taken together, the progressive/persistent biopsies in the Proliferative subtype have down-regulated expression of Module 9 compared with regressive biopsies that correlates with reduced signals from both innate and adaptive immune cell populations. 
     Immunofluorescence Reveals Progression-Associated Modulation of Macrophages and T Cells in Proliferative PMLs 
     In order to confirm the relationship between the immune cell types associated with Module 9 and histologic progression/persistence of PMLs in the Proliferative subtype, immunofluorescent staining of macrophages/monocytes (n=52 regions enumerated from n=16 subjects), CD4 (n=50 regions enumerated from n=17 subjects), and CD8 T cells (n=47 regions enumerated from n=16 subjects) was performed (Table 7). The results were analyzed across all subjects assayed within the Proliferative subtype and across the subset of subjects where the lesion outcome (progression/persistence versus regression) was concordant with the Module 9 GSVA score (denoted as concordant set). Staining of CD68, a pan macrophage (and tumor associated macrophage) marker, suggestive of M1 type macrophages, was increased in progressive/persistent lesions (p&lt;&lt;0.001 in the concordant set). In contrast, staining of CD163 in combination with CD68, thought to be suggestive of M2 type macrophages, were decreased among the progressive/persistent lesions in the Proliferative subtype (p&lt;&lt;0.001 using all subjects and p=0.0007 in the concordant set, respectively, linear model) ( FIG.  4 D- 4 E ). Additionally, CD4 T cells were increased (p&lt;&lt;0.001 in the concordant set, linear model) and CD8 T cells were decreased (p&lt;&lt;0.001 in the concordant set) in PMLs that progress/persist. Interestingly, among progressive/persistent lesions, the CD8 T cells had a distinct localization pattern (p=0.07 in the concordant set, linear model), where CD8 T cells both lined and were embedded within the epithelium in areas where dysplasia is present ( FIG.  4 D ). The immunofluorescence results did not reach significance, with the exception of CD163, when just the lesion outcome was used without regard to the Module 9 score. 
     Discussion 
     Lung squamous cell carcinoma (LUSC) is the second most common form of lung cancer and arises in the epithelial layer of the bronchial airways. It is often preceded by the development of lung squamous premalignant lesions (PMLs). The presence of dysplastic persistent and or progressive PMLs is a marker of increased risk for LUSC (6). Currently, however, effective tools to identify PMLs at highest risk of progression to invasive carcinoma are lacking (7). The development of markers predictive of disease progression will be important in identifying patients at highest risk for LUSC development and in identifying biological pathways exploitable for LUSC chemoprevention. Towards this goal, described herein is profiling via RNA-Seq bronchial brushes and endobronchial biopsies obtained from subjects undergoing longitudinal lung cancer screening by chest computed tomography (CT) and autofluorescence bronchoscopy. Four transcriptionally distinct groups of biopsies are identified, one of these labelled Proliferative and found to be associated with high-grade dysplasia. Patients with Proliferative PMLs can also be identified via gene expression measured from cells in the non-involved large airway epithelium. It was further found that persistent/progressive Proliferative PMLs are characterized by decreased expression of genes involved in interferon signaling and antigen processing/presentation pathways. Consistent with these gene expression findings it was found that progressive/persistent Proliferative PMLs are depleted for CD68+/CD163+ macrophages and CD8 T cells by immunofluorescence. Collectively, these data indicate both the potential to identify a subset of patients with progressive/persistent LUSC PMLs, who are at risk for developing invasive lung cancer, on the basis of airway gene expression; as well as the potential to decrease the risk for progression in these patients by augmenting the immune response associated with regression. 
     Previous studies indicate a range of genomic alterations associated with bronchial dysplasia. Increased expression of EGFR and Ki67 staining of epithelial cells is associated with increasing histologic severity and subsequent histologic progression (6, 17). Altered protein levels of TP53, CCND1, CCNE1, BAX, and BCL2 have been associated with CIS or lung cancer occurrence independent of histological grade (18). Telomere shortening and maintenance (19) and loss of heterozygosity in regions frequently detected in lung cancer (3p, 5q, 9p, 13q, 17p) have been observed in early hyperplasia/metaplasia lesions (20-22) and found to increase in frequency and size in higher-grade dysplasia. Genomic gains in loci containing SOX2, TP63, EGFR, MYC, CEPS, and CEPS are also associated with progression of high-grade dysplasia (23). Despite the numerous genomic alterations associated with PML histological grade and progression, a comprehensive PML molecular classification system to complement the pathologic classification of PML is lacking. Use of an unsupervised class discovery approach that led to the identification of four distinct molecular PML subtypes (Proliferative, Inflammatory, Secretory, and Normal-like). 
     The transcriptional patterns differentiating the PML subtypes are robust and a 22-gene panel identified in the Discovery Cohort can be used to distinguish between the different molecular subtypes in an independent Validation Cohort. Interestingly, while prior lung cancer history may influence airway gene expression and about two-thirds of the subjects have a prior history of lung cancer, we do not detect a significant association between lung cancer history and molecular subtype, and there is a similar diversity of molecular subtypes between biopsies collected from subjects with and without a lung cancer history. The Proliferative subtype is enriched with dysplastic PMLs from current smokers and is characterized by up-regulation of metabolic (OXPHOS/ETC/TCA) and cell cycle pathways and down-regulation of cilia-associated pathways. Previous work indicates increases in metabolic pathways in the airways of subjects with dysplastic lesions (13), in PMLs adjacent to LUSC tumor (24), and in smokers at high-risk for lung cancer (25) as well as increases in proliferation (via Ki67 levels, as mentioned above) that have been utilized as an endpoint in lung cancer chemoprevention (26, 27). Identification of patients with Proliferative lesions are useful to enrich lung cancer chemoprevention trials with high-risk subjects or to identify patients who would benefit from more frequent lung cancer screening. The Inflammatory subtype is predominated by PMLs from former smokers, but interestingly is not significantly enriched for dysplasia, despite similarly decreased expression of cilia-associated pathways, suggesting an abnormal epithelium. The Inflammatory subtype also shows increased expression of a gene module enriched for genes involved in inflammation and regulation of lymphocytes and leukocytes (Module 8). This gene module is also elevated in Secretory lesions predominated by lesions from current smokers and exhibiting increased expression of goblet cell markers. Interestingly, IL1B is part of this inflammation-related gene module, which is of great interest as the inhibition of IL1B has recently been shown to reduce lung cancer incidence (28). 
     Our prior work has extensively studied gene expression alterations in normal-appearing airway epithelium by profiling cells obtained via brushing the mainstem bronchus during bronchoscopy (8, 29,35). As part of this work, gene expression alterations were described that reflect the presence of bronchial dysplasia (31). In the current study, for the first time both bronchial brushes and endobronchial biopsies were collected during the same procedure allowing identification of gene expression differences in bronchial brushings from normal appearing airway which indicate the presence of Proliferative subtype PMLs. In both the Discovery and Validation cohorts, applying the predictor used to identify Proliferative subtype PMLs (based on PML biopsy gene expression) to the gene expression data from the normal-appearing airway brushings resulted in predictions of the Proliferative subtype that were very specific (91%) but not sensitive (31-38%). Brushes classified as Proliferative have increased expression of cell cycle pathways and decreased expression of cilia-associated genes, suggesting that they are more similar to squamous metaplasia than normal epithelium. Potentially, a subset of patients may harbor widespread airway damage that serves as a marker for the presence of this type of high-grade PML leading to modest sensitivity, but high specificity. In other cases, the area of damage that gives rise to these Proliferative PMLs may be more localized, and therefore potentially more difficult to detect by brushing contributing to decreased sensitivity. These findings indicate that therapeutics to target changes throughout the entire airway epithelium may be necessary in some subjects, whereas, more site-specific ablation (e.g. photodynamic therapy) may be more effective in certain cases. Another possibility and area of future research, is that a Proliferative subtype brush is a predictor of incident LUSC. 
     The molecular profiling of PMLs and the identification of gene co-expression modules also provides an opportunity to identify the molecular determinants of subsequent PML progression. One of the nine gene co-expression modules used to define the molecular subtypes was significantly different between biopsies that progress or persist compared to biopsies that regress within the Proliferative subtype in both the DC and VC cohorts. The module contains genes whose expression is decreased in the persistent/progressive biopsies that are involved in interferon signaling and antigen processing and presentation. These gene expression changes were correlated with a decreased abundance of innate and adaptive immune cells via computational prediction. By immunofluorescent staining of FFPE biopsy sections it was confirmed that the progressive/persistent Proliferative lesions with low Module 9 GSVA scores had fewer CD163+ macrophages and CD8+T cells and the CD8+T cells had a distinct localization pattern. These lesions also contained greater numbers of CD4+ T cells, and it will be important in future work to assess if these cells are T regulatory cells promoting an immune suppressive environment. 
     The presence of tumor-associated macrophages with the polarized phenotypes (M1 as pro-inflammatory or M2 as anti-inflammatory) has been associated with lung cancer prognosis. The presence of predominantly M2 macrophages, marked by the expression of CD163, has been associated with worse survival. However, in the context of lung PMLs this relationship is not well studied. The present finding that regressive Proliferative PMLs have more CD163+ cells and increased expression of genes involved in IFNg signaling is consistent with what has been seen in the PMLs that precede oral squamous cell carcinoma where the presence of CD163+ macrophages with active IFNg signaling is associated with better outcomes (36). Additionally, fewer CD8+ T cells and lower expression of HLA class I genes and B2M were observed in progressive/persistent lesions within the Proliferative subtype. Disruptions in proper T cell mediated immunosurveillence have been described in several studies showing that impaired HLA class I antigen processing and presentation including down-regulation or loss of B2M (37, 38) and interferon signaling (39) in lung tumors affects response and acquired resistance to checkpoint inhibitors. Lung tumors lacking an HLA-I complex had lower cytotoxic CD8+ lymphocyte infiltration, and this was also associated with lower levels of PD-L1. Additionally, studies have also suggested negative impacts on efficacy of check point inhibitors as well as survival in patients with LC that have tumors with increased CD4+ T cells expressing T regulatory markers (FOXP3, CD25) resulting in immunosuppressive state suggested to hinder the recruitment and effector functions of CD8+ T cells (40, 41). Future DNA sequencing data on the PMLs profiled here may indicate heterozygous or homozygous loss of B2M or mutations in other genes in the interferon and antigen processing and presentation pathways; however, even in the case of acquired resistance, mutations and copy number changes could not explain the down-regulation of these pathways across all subjects, suggesting that other epigenetic alterations or signaling pathways may play a role. In fact, epigenetic therapy, specifically DNA methyltransferase inhibitors (42), has been shown to enhance response to immune checkpoint therapy and up-regulate many of the genes down-regulated in progressive/persistent lesions within the Proliferative subtype including HLA class I genes (HLA-B and HLA-C), B2M, CD58, TAP1, immune-proteasome subunits PSMB9 and PSMB8, and the transcription factor IRF9. Unraveling the mechanisms of innate and adaptive immune down-regulation in this subset of PMLs will be important to identifying potential immunoprevention therapies. 
     The present data indicates that there are subtype-specific transcriptomic alterations predictive of subsequent LUSC premalignant lesion progression that are the result of a lack of infiltrating immune cells in the lesion microenvironment. These data suggest that biomarkers for determining PML subtype and assessing immune infiltration may have utility for the detection of aggressive PMLs that require more intensive clinical management and genes altered in these PMLs may serve as lung chemoprevention candidates. These biomarkers could either be measured directly in PML tissue, or as indicated by the present data, they can be measured in a surrogate tissue such as bronchial airway epithelium. A benefit of biomarkers predicting aggressive PML behavior measured in surrogate tissue is the potential that these biomarkers can also predict the behavior of PMLs not directly observed during bronchoscopy. 
     Materials and Methods 
     Subject Population and Sample Collection 
     Endobronchial biopsies and brushings were obtained from high-risk subjects undergoing lung cancer screening at approximately 1-year intervals by white light and auto-fluorescence bronchoscopy and computed tomography at Roswell. The bronchoscopy included visualization of the vocal cords, trachea, main carina, and orifices of the sub-segmental bronchi visible without causing trauma to the bronchial wall. All abnormal and suspicious areas are biopsied twice and the lung anatomic location is recorded ( FIG.  14   , Table 8). One biopsy was used for routine pathological evaluation and the other for molecular profiling. Additionally, a brushing was obtained from a normal appearing area of the left or right mainstem bronchus for research. Morphological criteria used to evaluate the biopsies are in accordance with World Health Organization (WHO) guidance (43). Eligibility for screening includes either a previous history of aerodigestive cancer and no disease at the time of enrollment or age greater than 50, a current or previous history of smoking for a minimum exposure of 20 pack-years and at least one additional risk factor including moderate chronic obstructive pulmonary disease (COPD) (defined as forced expiratory volume (FEV1)&lt;70%), confirmed asbestos related lung disease or a strong family history of lung cancer (at least 1-2 first degree relatives). All research specimens were stored in RNA Allprotect (Qiagen) and stored at −80 degrees C. 
     Subjects were selected that had biopsies collected in repeat locations via serial bronchoscopies; however, after RNA isolation, samples from 3 subjects had a single biopsy and 1 subject had a single brushing. mRNA sequencing was performed on a discovery cohort (DC) of samples comprising of endobronchial biopsies and brushes collected between 2010 and 2012 (n=30 subjects, n=197 biopsies, and n=91 brushings). mRNA sequencing was subsequently performed on a validation cohort (VC) of samples comprising of endobronchial biopsies and brushes collected between 2012 and 2015 (n=20 subjects, n=111 biopsies, and n=49 brushings). Brush histology was defined by the worst biopsy histology observed at the same time point. Biopsy progression/regression was defined for each biopsy based on the histology of the biopsy and the worst histology recorded for the same lung anatomic location in the future. Histology changes between normal, hyperplasia, and metaplasia were classified as “normal stable”, decreases in histological dysplasia grade or changes from dysplastic histology to normal/hyperplasia/metaplasia were classified as “regressive”, lack of future histological data was classified as “unknown”, and everything else was classified as “progressive/persistent.” The Institutional Review Boards at Boston University Medical Center and Roswell approved the study and all subjects provided written informed consent. 
     RNA-Seq Library Preparation, Sequencing, and Data Processing 
     Total RNA was extracted from endobronchial biopsies and bronchial brushings using miRNeasy™ Mini Kit or AllPrep™ DNA/RNA/miRNA Universal Kit (Qiagen). Sequencing libraries were prepared from total RNA samples using Illumina TruSeq™ RNA Kit v2 and multiplexed in groups of four using Illumina TruSeq™ Paired-End Cluster Kit. Each sample was sequenced on the Illumina HiSeq™ 2500 to generate paired-end 100-nucleotide reads. Demultiplexing and creation of FASTQ files were performed using Illumina CASAVA™ 1.8.2 or BaseSpace. Samples were aligned using hg19 and 2-pass STAR (44) alignment. Gene and transcript level counts were calculated using RSEM (45) using Ensembl™ v74 annotation. Quality metrics were calculated by STAR and RSeQC (46). Samples were excluded were sex annotation did not correlate with gene expression across CYorf15A (ENSG00000131002), DDX3Y (ENSG00000067048), KDM5D (ENSG00000012817), RPS4Y1 (ENSG00000129824), USP9Y (ENSG00000114374), and UTY (ENSG00000183878) (n=4 samples). Sample relatedness within a patient was confirmed using Peddy™ software (47). 
     Samples with a high-rate of heterozygosity (more than 3 standard deviations above the median) or samples with low relatedness to samples from the same patient (more than 3 standard deviations below the median) were removed from further analyses (n=11 samples, 2 brushes and 9 biopsies). Samples were subsequently divided into the discovery and validation cohorts (as outlined above) and by tissue type (biopsy or brush). Subsequent sample and gene filtering was conducted separately on each set as follows: First, EdgeR™ (48) was used to compute normalized data (library sizes normalized using TMM, trimmed mean of M-values, and log 2 counts per million computed) and genes were excluded that either had an interquartile range equal to zero or a sum across samples equal or less than 1. Samples were excluded based on values greater than 2 standard deviations from the mean for more than one of the following criteria: 1) mean Pearson correlation with all other samples calculated across all filtered genes 2) the 1 st  or 2 nd  principal components calculated using the filtered gene expression matrix 3) transcript integrity number (TIN, computed by RSeQC). After sample filtering, gene filtering was recomputed as described above on the final set of high-quality samples. The data are available from NCBI&#39;s Gene Expression Omnibus using the accession GSE109743. 
     Derivation of Molecular Subtypes 
     The DC biopsies (n=190 samples, n=16653 genes) and brushes (n=89 samples, n=16058 genes) were used to derive the molecular subtypes. Two additional RNA-Seq datasets were used during the derivation of the molecular subtypes: the TCGA squamous cell carcinoma (LUSC) tumors (10) (n=471 samples, n=17887 genes) and a dataset of tracheobronchial samples from mice treated with n-nitrosotris-(2-choroethyl)urea (NTCU) (n=25 samples, n=14897 genes). The mice develop lesions that are histologically and molecularly comparable to human lesions and that progress to LUSC and the samples represent a range of histology (normal, mild dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ (CIS), and LUSC tumor). The mouse data are available from NCBI&#39;s Gene Expression Omnibus using the accession ID GSE111091. Sample and gene filtering from the TCGA LUSC tumors and the mouse tissue were processed as described elsewhere herein. 
     Weighted correlation network analysis (9) (WGCNA) was used with default parameters to derive Modules of gene co-expression across the 4 datasets described above. Residual gene expression values adjusting for RNA quality (median TIN) and batch (Illumina flow cell) were used as input for WGCNA for the biopsy and brush datasets. For the mouse dataset, residual gene expression values adjusting for RNA quality (median TIN), mouse strain, and sample type (laser capture microdissected versus whole tissue) were used as input for WGCNA. Log 2 counts per million (cpm) values were used as input for WGCNA for the LUSC tumor samples. Gene sets were created for each co-expression Module for each dataset and then combined to create a compendium of gene sets generated from each of the 4 datasets. For each gene set in the compendium, the first principal component (PC1) was calculated across each z-score normalized dataset. For each dataset, a Pearson correlation matrix of PC1 values across all gene sets in the compendium was computed and thresholds were set as follows: r&gt;0.85 was set to 1 and r&lt;=0.85 set to 0. The four matrices were subsequently summed, and gene sets derived from biopsy co-expression Modules that were correlated to another non-biopsy derived gene set across all datasets were retained (n=9 Modules retained). The genes defining the retained biopsy Modules were required to be present in the biopsy Module and at least in one of the correlated gene sets. 
     The filtering process above yielded a reduced set of genes (n=3,936) that was used to define the molecular subtypes in the biopsy data. The residual gene expression values across the reduced set of genes for the discovery biopsies was used as input for consensus clustering (49). Consensus clustering was performed setting k (number of groups) to 10, the number of iterations to 1000, the subsampling to 80%, the clustering algorithm to partitioning around mediods, and the distance metric to Pearson correlation. The optimal value for k was 4 based on the relative change in area under the cumulative distribution function calculated based on the consensus matrix for each k. 
     Molecular Subtype Predictor 
     The DC biopsies across the filtered genes were used to derive a molecular subtype predictor. First, Pearson correlation metrics were determined between each gene and the Module eigengenes (PC1 for each of the 9 Modules). Genes were retained as part of a Module if the correlation value was the highest for the Module in which it was assigned. The average Pearson correlation of the retained genes to the Module eigengene was computed, and the number of genes chosen from each Module for the predictor was inversely proportional to this metric. Second, the genes most highly correlated to the Module eigengene were chosen to represent the Module in the predictor. The 22 genes resulting from this analysis across the DC biopsy data were used to train a nearest centroid predictor using the pamr package with a threshold of zero and predict the molecular subtype across the VC biopsies. Prior to predicting the molecular subtype of these test sets, the training and test sets were combat (50) adjusted and z-score normalized across combined training and test data. Using the methods described above we derived molecular subtypes using consensus clustering across the VC biopsies and compared these to the predicted subtypes. 
     Identification of Biological Processes Associated with Gene Modules and Molecular Subtypes 
     Biological processes and pathways enriched in each of the nine Modules used to discover the molecular subtypes in the DC were identified using EnrichR (51). Each Module was separated into genes positively or negatively correlated with the Module eigengene, the Ensembl IDs were converted to Gene Symbols using biomaRt, and the following databases were queried: GO Biological Process 2015, KEGG 2016, WikiPathways 2016, TargetScan microRNA, Transcription Factor PPIs, TRANSFAC and JASPAR PWMs, OMIM Disease, Reactome 2016, and Biocarta 2016. Processes/pathways with an FDR&lt;0.05 were considered to be significantly enriched. The contribution of each gene Module to the DC biopsy molecular subtypes was evaluated by testing if GSVA (14) scores for each Module were significantly (FDR&lt;0.05) associated with the molecular subtypes using a linear mixed effect model with patient as a random effect via limma. 
     Identification of Clinical and Biological Phenotype Associations with Molecular Subtype 
     The molecular subtypes in the DC biopsies were annotated according to the behavior of each gene Module by calculating whether or not GSVA (14) scores for each Module were significantly up- or down-regulated (FDR&lt;0.05) in a particular molecular subtype versus all other samples using a linear mixed effects model with patient as a random effect via limma. Additionally, the biological pathways and transcription factors associated with each subtype were identified using GSEA (52) and mSigDB (53) gene sets using genes ranked by the t-statistic for their association with each subtype. The ranked lists were created using the limma (54) and edgeR (48) packages to identify differentially expressed genes associated with subtype membership. 
     Each linear model used voom-transformed (55) data and included membership in the subtype of interest, batch, and RNA quality (TIN) as covariates and patient as a random effect. Pathways enriched in the ranked lists (FDR&lt;0.05) were used to annotate the molecular subtypes. FDR values for individual genes were derived from this analysis or analogous models using only samples of normal/hyperplasia histology or dysplasia histology. 
     For the DC and VC biopsies, residual gene expression values were used to predict smoking status, LUSC tumor subtype, and the relative abundance of epithelial and immune cells for each sample. Smoking status (current versus former/never) was predicted for each sample as described previously (13). Smoking status was determined at each time point for each subject by calculating the mean of the prediction scores (&gt;0 for current prediction and &lt;0 for former/never prediction) across all biopsies and brushes sampled. The LUSC tumor subtype was determined as described previously (11) across the genes predictive of the LUSC molecular subtype (12). The ESTIMATE algorithm (56) was used to infer relative epithelial, stromal, and immune cell content. Immune cell type specific signatures from Bindea et al. (15) and epithelial cell type specific signatures from Dvorak et al. (50) were used to generate GSVA(14) scores across samples for each signature. Additionally, residual gene expression values calculated using log RPKM values were inputted into the xCell (16) to infer relative abundances of 64 different cell types. The above categorical phenotypes along with additional clinical variables such as biopsy histology, subject, previous lung cancer history, sex, and biopsy progression/regression status were associated with molecular subtype using Fisher&#39;s Exact Test. Continuous variables were associated with molecular subtype using a linear model via limma. 
     In order to characterize the molecular alterations associated with lesion outcome, a linear mixed effects model was used to assess module GSVA score differences between progressive/persistent versus regressive lesions within each molecular subtype with patient as a random effect via limma. We estimated differences in the immune cell content (separately for xCell and Bindea et al.) between progressive/persistent versus regressive lesions in the Proliferative subtype via a linear mixed effects model correcting for epithelial cell content (‘Epithelial’ in xCell and ‘Normal mucosa’ in Bindea et al.) and patient as a random effect. We focused on cell types that were significantly different (FDR&lt;0.05) between progressive/persistent versus regressive lesions in the Proliferative subtype in both the discovery and validation cohorts. 
     Relationship Between the Biopsies and Brushes 
     It was desired to quantify the predictive performance of the brush with regards to the presence of a biopsy of the Proliferative subtype. A subset of the 22-gene molecular subtype predictor was used to predict the presence or absence of the Proliferative subtype across the DC and VC brushes and biopsies. Specifically, 8 genes (out of the 22) were used that corresponded to Modules 4 through 7 (significantly up- or down-regulated in the Proliferative subtype) to classify samples as Proliferative or not using the same methodology described above for the molecular subtype predictor. Sensitivity and specificity performance metrics were calculated based on the ability of a Proliferative subtype prediction in the DC or VC brushes to indicate the presence of at least one biopsy of the Proliferative subtype. In order to further understand the Proliferative subtype predictions in the brushes, the behavior of the modules that define the Proliferative subtype in the DC biopsies (based on methods above) was analyzed across the DC and VC brushes. 
     Immunofluorescent Staining and Quantitation 
     Standard formalin fixation and embedding techniques were employed at Roswell where 5-micron sections were cut from the FFPE samples used for the routine pathological evaluation at Roswell (Table 7). Prior to staining, samples were de-waxed with xylene and rehydrate through a graded series of ethanol solutions. AR or citrate buffer was used for antigen retrieval, tissue was incubated with primary antibodies overnight at 4° C. and probed with secondary antibodies with fluorescent conjugates (Invitrogen Alexa Fluor 488, 594, 647) for 1 hour at room temperature. Immunostaining was performed using the primary antibodies listed in Table 9. Imaging was performed using an Aperio Slide Scanner for scoring and a Carl Zeiss Axio (20× and 40× objectives) and a Carl Zeiss LSM 710 NLO confocal microscope for capturing additional images. Digital slides were analyzed with the Definiens Tissue Studio (Definiens Inc.) for the enumeration of immunofluorescence staining. The enumeration of the immunofluorescence scored each stain including DAPI positive cells. The enumeration was conducted on different regions (independent areas of tissue) present on a slide (1-5 regions/biopsy) for each biopsy. For each region, the percentage of positively staining cells for a given protein was calculated by dividing the number of positively stained cells by the total number of DAPI positive cells. A binomial mixed effects model via the 1me4 R package was used to assess differences in the percentages of cells staining positive for a given protein in each region between progressive/persistent versus regressive biopsies using the total cells stained in each region as weights and adjusting for the slide number as a random effect. The models were used across samples from the Proliferative subtype and across samples from the Proliferative subtype where the biopsy outcome (progressive/persistent versus regressive) agreed with the Module 9 GSVA score (scores less than 0 are associated with progression/persistence and scores greater than 0 are associated with regression). Each region was also qualitatively scored as either positive or negative for having a distinct CD8 T cell localization pattern where cells lined and were embedded within the epithelium. 
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         56. K. Yoshihara, M. Shahmoradgoli, E. Martinez, R. Vegesna, H. Kim, W. Tones-Garcia, V. Treviño, H. Shen, P. W. Laird, D. A. Levine, S. L. Carter, G. Getz, K. Stemke-Hale, G. B. Mills, R. G. W. Verhaak, Inferring tumour purity and stromal and immune cell admixture from expression data,  Nat Commun  4, 2612 (2013). 
       
    
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
             
            
               
                 Demographic and Clinical Annotation on Subjects in both the  
               
               
                 Discovery and Validation cohorts. Statistical tests between the  
               
               
                 Discovery and Validation cohorts were performed using 
               
               
                 Fisher&#39;s Exact Test for categorical variables and Student&#39;s  
               
               
                 T-Test for continuous variable. Percentages are 
               
               
                 reported for categorical variables and mean and standard  
               
               
                 deviations are reported for continuous variables. 
               
            
           
           
               
               
               
               
            
               
                   
                 Discovery  
                 Validation  
                   
               
               
                   
                 Cohort 
                 Cohort 
                   
               
               
                   
                 (n = 30  
                 (n = 20  
                 p- 
               
               
                 Variable 
                 Subjects) 
                 Subjects) 
                 value 
               
               
                   
               
               
                 Average # Biopsies/Subject 
                 6.6 (5.7) 
                 5.25 (2.9) 
                 0.3 
               
               
                 Average # Bronchoscopies/Subject 
                 2.8 (1.5) 
                 2.4 (0.8) 
                 0.27 
               
               
                 Average Time Between  Bronchoscopies (Days) 
                 368.2 (201.4) 
                 360.1 (212.5) 
                 0.87 
               
               
                 Male 
                 15/30 (50) 
                 12/20 (60) 
                 0.57 
               
               
                 White 
                 27/30 (90) 
                 17/20 (85) 
                 0.67 
               
               
                 Age (at Baseline Clinical Visit) 
                 58.8 (7.6) 
                 58.7 (8.3) 
                 0.97 
               
               
                 Ever smoker (at Baseline  
                 29/30 (96.7) 
                 19/20 (95) 
                 1 
               
               
                 Clinical Visit) 
                   
                   
                   
               
               
                 Prior History of Lung Cancer 
                 21/30 (70) 
                 12/20 (60) 
                 0.55 
               
               
                 COPD (FEV1/FVC &lt;=0.7, at  Baseline Clinical Visit) 
                 17/27 (63.0) 
                 8/18 (44.4) 
                 0.24 
               
               
                 GOLD 1 (FEV1% &gt;80) 
                 2/27 (7.4) 
                 2/18 (11.1) 
                 1 
               
               
                 GOLD 2 (FEV1% &lt;80 and &gt;50) 
                 12/27 (44.4) 
                 5/18 (27.8) 
                 0.35 
               
               
                 GOLD 3 (FEV1% &lt;50 and &gt;30) 
                 3/27 (11.1) 
                 1/18 (5.6) 
                 0.64 
               
               
                 Occupational Asbestos 
                 13/30 (43.3) 
                 9/20 (45) 
                 1 
               
               
                 Occupational High-Risk Job 
                 14/30 (46.7) 
                 12/20 (60) 
                 0.4 
               
               
                   
               
               
                   
                 Discovery 
                 Validation 
                   
               
               
                   
                 Cohort  
                 Cohort  
                 P- 
               
               
                 Variable 
                 (n = 30) 
                 (n = 20) 
                 value 
               
               
                   
               
               
                 Average # Biopsies/Subject 
                 6.6 (5.7) 
                 5.25 (2.9) 
                 0.3 
               
               
                 Average # Bronchoscopies/Subject 
                 3.1 (1.6) 
                 2.5 (0.7) 
                 0.08 
               
               
                 Average Time Between  
                 348.6 (197.5) 
                 366.8 
                 0.69 
               
               
                 Bronchoscopies (Days) 
                   
                 (208.3) 
                   
               
               
                 Male 
                 15/30 (50) 
                 12/20 (60) 
                 0.81 
               
               
                 White 
                 27/30 (90) 
                 17/20 (85) 
                 1 
               
               
                 Age (at Baseline Clinical Visit) 
                 58.8 (7.6) 
                 58.7 (8.3) 
                 0.97 
               
               
                 Ever smoker (at Baseline  
                 29/30 (96.7) 
                 19/20 (95) 
                 1 
               
               
                 Clinical Visit) 
                   
                   
                   
               
               
                 Pack-years 
                 49.8 (22.1) 
                 41.3 (20.7) 
                 0.17 
               
               
                 Prior History of Lung Cancer 
                 21/30 (70) 
                 12/20 (60) 
                 0.82 
               
               
                 LUSC 
                 5/30 (16.7) 
                 5/20 (25) 
                 0.73 
               
               
                 Other 
                 16/30 (53.3) 
                 7/20 (35) 
                 0.6 
               
               
                 COPD (FEV1/FVC &lt;=0.7, at  
                 17/27 (63.0) 
                 8/18 (44.4) 
                 0.61 
               
               
                 OLD 1 (FEV1% &gt;80) 
                 2/27 (7.4) 
                 2/18 (11.1) 
                 1 
               
               
                 Baseline Clinical Visit) 
                   
                   
                   
               
               
                 GOLD 2 (FEV1% &lt;80 and &gt;50) 
                 12/27 (44.4) 
                 5/18 (27.8) 
                 0.56 
               
               
                 GOLD 3 (FEV1% &lt; 50 and &gt;30) 
                 3/27 (11.1) 
                 1/18 (5.6) 
                 1 
               
               
                 Occupational Asbestos 
                 13/30 (43.3) 
                 9/20 (45) 
                 1 
               
               
                 Occupational High-Risk Job 
                 14/30 (46.7) 
                 12/20 (60) 
                 0.62 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
               
                   
               
             
            
               
                 Clinical Annotation on Samples in both the Discovery and Validation cohorts. 
               
               
                 Statistical tests between the Discovery and Validation cohorts within either the biopsies or brushes were 
               
               
                 performed using Fisher&#39;s Exact Test and percentages are reported. 
               
            
           
           
               
               
               
               
            
               
                 Variable 
                 Discovery Cohort 
                 Validation Cohort 
                 P-value 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Sample Type 
                 Biopsies 
                 Brushes 
                 Biopsies 
                 Brushes 
                 Biopsies 
                 Brushes 
               
               
                   
               
               
                 Histology 
                   
                   
                   
                   
                 0.05 
                 0.42 
               
               
                 Normal 
                 38/190 (20) 
                 6/89 (6.7) 
                 23/105 (21.9) 
                 0/48 (0) 
                   
                   
               
               
                 Hyperplasia 
                 30/190 (15.8) 
                 11/89 (12.4) 
                 31/105 (29.5) 
                 9/48 (18.8) 
                   
                   
               
               
                 Metaplasia 
                 46/190 (24.2) 
                 15/89 (16.9) 
                 14/105 (13.3) 
                 9/48 (18.8) 
                   
                   
               
               
                 Mild Dysplasia 
                 21/190 (11.1) 
                 9/89 (10.1) 
                 13/105 (12.4) 
                 6/48 (12.5) 
                   
                   
               
               
                 Moderate Dysplasia 
                 38/190 120) 
                 30/89 (33.7) 
                 20/105 (19.0) 
                 18/48 (37.5) 
                   
                   
               
               
                 Severe Dysplasia 
                 12/190 (6.3) 
                 17/89 (19.1) 
                 4/105 (3.8) 
                 6/48 (12.5) 
                   
                   
               
               
                 CIS 
                 1/130 (0.5) 
                 0/89 (0) 
                 0/105 (0) 
                 0/48 (0) 
                   
                   
               
               
                 Tumor 
                 0/190 (0) 
                 1/89 (1.1) 
                 0/105 (0) 
                 0/48 (0) 
                   
                   
               
               
                 Unknown Histology 
                 4/190 (2.1) 
                 0/85 (0) 
                 0/105 (0) 
                 0/48 (0) 
                   
                   
               
               
                 Current smoker  
                 119/190 (62.6) 
                 44/89 (49.4) 
                 38/105 (36.2) 
                 20/48 (41.7) 
                 1.80E−05 
                 0.47 
               
               
                 (Genomic prediction) 
                   
                   
                   
                   
                   
                   
               
               
                 Progression Status 
                   
                   
                   
                   
                 0.39 
                   
               
               
                 Normal/Stable 
                 47/190 (24.7) 
                   
                 35/105 (33.3) 
                   
                   
                   
               
               
                 Progressive/Persistent 
                 44/190 (23.2) 
                   
                 20/105 (19.0) 
                   
                   
                   
               
               
                 Regressive 
                 30/190 (15.8) 
                   
                 18/105 (17.1) 
                   
                   
                   
               
               
                 Unknown 
                 69/190 (36.3) 
                   
                 32/105 (30.5) 
                   
                   
                   
               
               
                 Histology 
                   
                   
                   
                   
                 0.05 
                 0.42 
               
               
                 Normal 
                 38/190 (20) 
                 6/89 (6.7) 
                 23/105 (21.9) 
                 0/48 (0) 
                   
                   
               
               
                 Hyperplasia 
                 130/89 (33.7) 
                 11/89 (12.4) 
                 31/105 (29.5) 
                 9/48 (18.8) 
                   
                   
               
               
                 Metaplasia 
                 46/190 (24.2) 
                 15/89 (16.9) 
                 14/105 (13.3) 
                 9/48 (18.8) 
                   
                   
               
               
                 Mild Dysplasia 
                 21/190 (11.1) 
                 9/89 (10.1) 
                 13/105 (12.4) 
                 6/48 (12.5) 
                   
                   
               
               
                 Moderate Dysplasia 
                 38/190 (20) 
                 30/89 (33.7) 
                 20/105 (19.0) 
                 18/48 (37.5) 
                   
                   
               
               
                 Severe Dysplasia 
                 12/190 (6.3) 
                 17/89 (19.1) 
                 4/105 (3.8) 
                 6/48(12.5) 
                   
                   
               
               
                 CIS 
                 1/190 (0.5) 
                 0/89 (0) 
                 0/105 (0) 
                 0/48 (0) 
                   
                   
               
               
                 Tumor 
                 0/190 (0) 
                 1/89 (1.1) 
                 0/105 (0) 
                 0/48 (0) 
                   
                   
               
               
                 Unknown Histology 
                 4/190 (2.1) 
                 0/89 (0) 
                 0/105 (0) 
                 0/48 (0) 
                   
                   
               
               
                     ent smoker (Genomic prediction) 
                 122/190 (64.3) 
                 50/89 (56.2) 
                 53/105 (50.5) 
                 27/48 (56.3) 
                 0.03 
                 1 
               
               
                 Progression Status 
                   
                   
                   
                   
                 0.39 
                   
               
               
                 Normal/Stable 
                 47/190 (24.7) 
                   
                 35/105 (33.3) 
                   
                   
                   
               
               
                 Progressive/Persistent 
                 44/190 (23.2) 
                   
                 20/105 (19.0) 
                   
                   
                   
               
               
                 Regressive 
                 30/190 (15.8) 
                   
                 18/105 (17.1) 
                   
                   
                   
               
               
                 Unknown 
                 69/190 (36.3) 
                   
                 32/105 (30.5) 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 Summary of Molecular Subtype Characteristics in the Discovery Cohort. For 
               
               
                 each molecular subtype, significant associations are reported with each of the 9 gene modules, clinical 
               
               
                 characteristics, canonical cell type epithelial and white blood cell gene markers, and pathways. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                 PROLIFERATIVE 
                   
               
               
                 Up-regulated Modules 
                 4, 5, 7 
               
               
                 Down-regulated Modules 
                 6 
               
               
                 Clinical Characteristics 
                 Current smoking (   %) Dysplastic biopsies (63%) 
               
               
                 Biological Charcteristics 
                 SCC subytpes-Classical and Basal; TUB1A1, SCGB1A1  down-regulated: KRT5, KI67 up-regulated 
               
               
                 Pathways 
                 Cell cycle: BUB1B/1/3, CHEK2/2, CDK1/2/4/6; E2P1/3/2/4;  
               
               
                   
                 MCM4/3/5/5/7, TP53, R81 
               
               
                   
                 DNA repair: TP53, PARP1, RADS1, BRCA2,  
               
               
                   
                 FANCA/D2/G/E/M/C, XRCCS/6. ERCC6 
               
               
                   
                 Oxidative Phosphorylation and Electron Transport Chain: AtP synthases,  
               
               
                   
                 NADH-ubiquinone oxidoreductases, cytochrome C oxidases 
               
               
                 TFs 
                 E2F 
               
               
                 INFLAMMATORY 
                   
               
               
                 Up-regulated Modules 
                 1, 2, 7, 8 
               
               
                 Down-regulated Modules 
                 6 
               
               
                 Clinical Characteristics 
                 Former smoking (56%) non-dysplastic biopsies (68%) 
               
               
                 Biological Charcteristics 
                 SCC subytpes-Secretory; TUB1A1, MUC5AC down-regulated 
               
               
                 Pathways 
                 Extracellular matrix, focal adhesion, and integrin pathways:  colagen, integrin, and laminin genes 
               
               
                   
                 Cytokine/chemokine: CCL2/14/19/21/28, CXCL12/14/5, CCR1/2/3/4/5,  IL1B, IL11RA, IL17RB, IL1R1, IL3RA, 
               
               
                   
                 EGF, IL15, CK3CR1, TGFB1/B2/B3, KIT 
               
               
                   
                 Down-regulation of oxidative phosphorylation, respiratory  
               
               
                   
                 electron transport, cell cycle 
               
               
                 TFs 
                 SRF 
               
               
                 SECRETORY 
                   
               
               
                 Up-regulated Modules 
                 6, 8 
               
               
                 Down-regulated Modules 
                 1, 2, 5, 7 
               
               
                 Clinical Characteristics 
                 Current smoking (63%) non-dysplastic biopsies (66%) 
               
               
                 Biological Charcteristics 
                 SCC subtypes-Secretory: CD45, MUCSAC, TUB1A1  up-regulated; KI67, KRT5 down-regulated 
               
               
                 Pathways 
                 Down-regulated of extracellular matrix, focal adhesion, integrin pathways 
               
               
                 TFs 
                 Down-regulation of E2F 
               
               
                 NORMAL 
                   
               
               
                 Up-regulated Modules 
                 1, 6 
               
               
                 Down-regulated Modules 
                 8, 9 
               
               
                 Clinical Characteristics 
                 Former smoking (65%) non-dysplastic biopsies (75%) 
               
               
                 Biological Charcteristics 
                 CD45, MUC5AC, KI67 down-regulated: SCGB1A1, KRT5, TUB1A1 up-regulated 
               
               
                 Pathways 
                 Core extracellular matrix genes: collagen and lamin genes, WISP1/2 
               
               
                   
                 Down-regulation of innate and adaptive Immunity: HLA genes,  IRF1/4/7/8, TLR2/4/6/8/10, IKBKB 
               
               
                 TFs 
                 Down-regulation of PEA3, IRF, NFKB 
               
               
                 PROLIFERATIVE 
                   
               
               
                 Up-regulated Modules 
                 4, 5, 7 
               
               
                 Down-regulated Modules 
                 6 
               
               
                 Clinical Characteristics 
                 Current smoking (88%), Dysplastic biopsies (63%) 
               
               
                 Biological Charcteristics 
                 LUSC subytpes-Classical and basal; TUB1A1, SCG81A1  down-regulated; KRT5, KI67 up-regulated 
               
               
                 Pathways 
                 Cell cycle: BUB1B/1/3, CHEX1/2, CDK1/2/4/6,  
               
               
                   
                 E2F3/3/2/4, MCM4/3/5/6/7, TP53, RB1 
               
               
                   
                 DNA repair: TP53, PARP1, RAD51, BRCA2,  
               
               
                   
                 FANCA/D2/G/E/M/C, XRCC5/6, ERCC6 
               
               
                   
                 Oxidative Phosphorylation and Electron Transport Chain: ATP synthases,  
               
               
                   
                 NADH-ubiquinone oxidoreductases, cytochrome C oxidases 
               
               
                 Transcription Factors 
                 E2F 
               
               
                 INFLAMMATORY 
                   
               
               
                 Up-regulated Modules 
                 1, 2, 7, 8 
               
               
                 Down-regulated Modules 
                 4, 5, 6 
               
               
                 Clinical Characteristics 
                 Former smoking (59%), non-dysplastic biopsies (68%) 
               
               
                 Biological Charcteristics 
                 LUSC subytpes-Secretory TUB1A1, MUC5AC down-regulated 
               
               
                 Pathways 
                 Extracellular matrix, focal adhesion, and ntegrin pathways:  collagen, itegrin, and laminin genes 
               
               
                   
                 Cytokine/chemokine: CCL2/14/19/21/28, CXCL12/14/5, CCR1/2/3/4/5, IL18, IL1IRA,  
               
               
                   
                 IL17R8, IL1R1, IL3RA, EGF, IL15, CX3CR1, TGF81/82/83, KIT 
               
               
                   
                 Down-regulation of oxidative phosphorylation respiratory electron transport, cell cycle 
               
               
                 Transcription Factors 
                 SRF 
               
               
                 SECRETORY 
                   
               
               
                 Up-regulated Modules 
                 6, 8 
               
               
                 Down-regulated Modules 
                 1, 2, 5, 7 
               
               
                 Clinical Characteristics 
                 Current smoking (77%) non-dyplastic biopsies (66%) 
               
               
                 Biological Charcteristics 
                 LUSC subytpes-Secretory; CD45, MUC5AC, TUB1A1  up-regulated; KI67, KRT5 down-regulated 
               
               
                 Pathways 
                 Down-regulation of extracellular matsix, focal adhesion, integrin pathways 
               
               
                 Transcription Factors 
                 Down-regulation of E2F 
               
               
                 NORMAL-LIKE 
                   
               
               
                 Up-regulated Modules 
                 1, 6 
               
               
                 Down-regulated Modules 
                 8, 9 
               
               
                 Clinical Characteristics 
                 Former smoking (65%) non-dysplastic biopsies (75%) 
               
               
                 Biological Charcteristics 
                 CD45, MUC5AC, KI67 down-regulated; SCGB1A1, KRT5, TUB1A3 up-regulated 
               
               
                 Pathways 
                 Core Extracellular matrix genes: collagen and laminin genes, WISP1/2 
               
               
                   
                 Down-regulation of innate and adaptive immunity:  HLA genes, IRF1/4/7/8, TLR2/4/6/8/10, IKBK5 
               
               
                 Transcription Factors 
                 Down-regulation of PEA3, IRF, NFKB 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     Example 2: Supplemental Material for Example 1 
     Materials and Methods 
     N-nitrosotris-(2-choroethyl)urea (NTCU) mouse sample collection and library preparation. We have previously collected and banked RNA from 40 fresh frozen whole lung sections (curls) and laser microdissected (LCM) tissue isolated with an Acrutus Pixcell™ II, from SWR/J and A/J mice treated with NTCU. Mice had been treated topically with 15 or 25 umol NTCU (25 ul of 40 mM NTCU for 15 or 25 weeks) as part of a study performed in accordance with IACUC approved protocol at RPCC. Samples include examples of: normal (SWR/J n=3 LCM &amp; 3 curls &amp; A/J n=2 LCM &amp; 1 curl), metaplasia/mild dysplasia (SWR/J n=5 LCM &amp; 2 curls), moderate dysplasia (SWR/J n=7 LCM &amp; 4 curls &amp; A/J n=2 LCM &amp; 1 curls), and severe dysplasia (SWR/J n=3 LCM &amp; 2 curls), and carcinoma in situ/LUSC (A/J n=2 LCM &amp; 2 curls). Samples were extracted using the Qiagen mi-RNAeasy kit according to manufacturer&#39;s protocol. Sequencing libraries will be prepared from total RNA samples using Illumina® TruSeq® RNA Sample Preparation Kit v2. Each sample was sequenced five per lane on the Illumina® HiSeq 2500 to generate single-end 50-nucleotide reads. 
     
       
         
           
               
            
               
                   
               
               
                 Histological Classification of the NTCU Mouse Samples RNA Sequenced 
               
               
                 (n = collected/n = passed QC after sequencing) 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 Moderate/ 
                   
                   
                   
               
               
                 Mouse 
                 Sample 
                   
                 Mild 
                 Severe 
                 Severe 
                 CIS/SCC 
               
               
                 Stains 
                 Type 
                 Normal 
                 Dysplasia 
                 Dysplasia 
                 Dysplasia 
                 Tumor 
                 Total 
               
               
                   
               
               
                 A/J 
                 LCM 
                 2/2 
                 — 
                 2/2 
                 — 
                 2/1 
                 6/5 
               
               
                 A/J 
                 Curls 
                 1/1 
                 — 
                 1/1 
                 — 
                 2/1 
                 4/3 
               
               
                 SWR/J 
                 LCM 
                 4/1 
                 5/3 
                 7/3 
                 3/1 
                   
                 19/8  
               
               
                 SWR/J 
                 Curls 
                 3/3 
                 2/2 
                 4/3 
                 2/1 
                   
                 11/9  
               
               
                   
                   
                   
                   
                   
                   
                 Total 
                 40/25 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Mean RIN values 
                 4.0(1.8) 
                 3.8(0.5) 
                 3.3(0.6) 
                 2.55(0.1) 
                 3.4(1.2) 
                   
               
               
                 (SD) 
               
               
                   
               
            
           
         
       
     
     NTCU mouse data processing. Demultiplexing and creation of FASTQ files were performed using Illumina CASAVA 1.8.2. Trimmomatic was used to trim adapter sequences as well as to trim reads of poor quality using the following parameters: ILLUMINACLIP:TruSeq3-SE.fa:2:30:10, LEADING:20, TRAILING:20, SLIDINGWINDOW:4:20, and MINLEN:20. After trimming, greater than 99% of reads were retained in all samples. Samples were subsequently aligned using mm9 and 2-pass STAR(44) alignment. Gene and transcript level counts were calculated using RSEM(45) using Ensembl annotation. Quality metrics were calculated by STAR and RSeQC(46). Initially, 15 samples were removed based on percent of uniquely aligned reads (compared to total reads) less than 15%. Subsequent sample and gene filtering was conducted separately on each set as follows: First, EdgeR(48) was used to compute normalized data (library sizes normalized using TMM, trimmed mean of M-values, and log 2 counts per million computed) and genes were excluded that either had an interquartile range equal to zero or a sum across samples equal or less than 1. Samples were excluded based on values greater than 2 standard deviations from the mean for 1) mean Pearson correlation with all other samples calculated across all filtered genes 2) the 1st or 2nd principal components calculated using the filtered gene expression matrix 3) transcript integrity number (TIN, computed by RSeQC). After sample filtering, gene filtering was recomputed as described above on the final set of high-quality samples. The data are available from NCBI&#39;s Gene Expression Omnibus using the accession GSE111091. 
     Immunofluorescent quantification of cell type and proliferative markers. Basal and ciliated cell type markers (KRT5 and TUB1A1) and the proliferative marker (KI67) were manually enumerated for all epithelium within a biopsy in reference to DAPI staining, with a minimum of 500 cells counted per biopsy. The enumeration was conducted on different regions (independent areas of tissue) present on a slide (1-4 regions/biopsy) for each biopsy. A percent of positively stained cells was calculated for each marker in each region enumerated. A binomial mixed effects model via the 1me4 R package was used to assess differences in the percentages of cells staining positive for a given protein in each region between the molecular subtypes using the total cells stained in each region as weights and adjusting for patient as a random effect. 
     TCGA SCC tumors data processing. Log 2 transcript per million data across 20,500 genes from 476 LUSC tumors was obtained from Campbell (10) et al. Genes were excluded that either had an interquartile range equal to zero or a sum across samples equal or less than 1. Samples were excluded based on values greater than 2 standard deviations from the mean for more than one of the following criteria: 1) mean Pearson correlation with all other samples calculated across all filtered genes 2) the 1st or 2nd principal components calculated using the filtered gene expression matrix 3) transcript integrity number (TIN, computed by RSeQC). After sample filtering, gene filtering was recomputed as described above (n=17,887 genes) on the final set of high-quality samples (n=471 tumors). 
     Table 5 depicts pathways enriched in the Gene Modules. Enrichr results (FDR&lt;0.05) for selected pathways associated with each gene modules. 
     
       
         
           
               
               
               
               
               
             
               
                   
               
               
                   
                   
                 Biological  
                   
                 FDR for 
               
               
                   
                   
                 Pathways 
                   
                 Difference 
               
               
                   
                 Number 
                 Associated  
                   
                 between 
               
               
                 Module 
                 of 
                 with Gene 
                   
                 Molecular 
               
               
                 Number 
                 Genes 
                 Modules 
                 Key Genes 
                 Subtypes 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1 
                 514 
                 Extracellular Matrix/ 
                 Collagens, Lamins, 
                 2.70E−36 
               
               
                   
                   
                 Cell Adhesion 
                 TGFb 
                   
               
               
                 2 
                 939 
                 mRNA processing  
                 RBMs &amp; SRSF 
                 7.20E−05 
               
               
                   
                   
                 and splicing 
                   
                   
               
               
                 3 
                 20 
                 Transcriptional 
                 JUN &amp; FOS 
                 1.90E−01 
               
               
                   
                   
                 regulation in response 
                   
                   
               
               
                   
                   
                 to stimuli-(AP-1) 
                   
                   
               
               
                   
                   
                 Immediate/Early 
                   
                   
               
               
                   
                   
                 response genes 
                   
                   
               
               
                 4 
                 64 
                 OXPHOS/ETC/TCA 
                 COXs &amp; NDUFs 
                 3.30E−07 
               
               
                 5 
                 209 
                 Cell Cycle/DNA 
                 PCNA, TOP2A,  
                 2.00E−31 
               
               
                   
                   
                 replication/DNA 
                 CDC, AURK,  
                   
               
               
                   
                   
                 repair 
                 RAD, XRCC 
                   
               
               
                 6 
                 1295 
                 Cilium organization 
                 FOXJ1, DYNC 
                 6.60E−57 
               
               
                   
                   
                 and assembly 
                   
                   
               
               
                 7 
                 180 
                 Ribosomal Proteins/ 
                 RPLs &amp; RPSs 
                 1.90E−13 
               
               
                   
                   
                 Translation 
                   
                   
               
               
                 8 
                 603 
                 Immune Activation 
                 CD8A, CD86,  
                 3.30E−07 
               
               
                   
                   
                 and Inflammatory 
                 GATA, STAT,  
                   
               
               
                   
                   
                 Response 
                 IL1B, CD163, 
                   
               
               
                   
                   
                 (leukocyte/lymphocyte 
                 CD68 
                   
               
               
                   
                   
                 regulation) 
                   
                   
               
               
                 9 
                 112 
                 Interferon signaling 
                 SP100, HLAs,  
                 1.30E−02 
               
               
                   
                   
                 and Antigen 
                 STAT1 
                   
               
               
                   
                   
                 Processing and 
                   
                   
               
               
                   
                   
                 Presentation 
                   
                   
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Molecular Subtype associations with Clinical and Biological  
               
               
                 Characteristics within the Discovery Cohort (DC) and the Validation  
               
               
                 Cohort (VC). Statistical tests within the Discovery and 
               
               
                 Validation cohorts were performed using Fisher&#39;s Exact 
               
               
                 Fisher&#39;s Exact Test Molecular Subtype V. Variable 
               
            
           
           
               
               
               
            
               
                 Variable 
                 DC P-value 
                 VC P-value 
               
               
                   
               
               
                 Genomic Smoking Status 
                 1.00E−07 
                 9.64E−03 
               
               
                 Subject 
                 9.66E−05 
                 5.87E−03 
               
               
                 Subject/Time 
                 6.96E−04 
                 1.40E−02 
               
               
                 Histology 
                 6.75E−03 
                 9.99E−08 
               
               
                 Location 
                 2.57E−02 
                 6.69E−01 
               
               
                 Subject/Location 
                 6.01E−02 
                 1.95E−01 
               
               
                 Asbestos Exposure 
                 1.23E−01 
                 7.47E−02 
               
               
                 Lung Cancer History 
                 1.32E−01 
                 9.92E−01 
               
               
                 Progression Status 
                 1.60E−01 
                 1.67E−05 
               
               
                 High-risk Job 
                 4.31E−01 
                 8.30E−01 
               
               
                 Sex 
                 5.62E−01 
                 8.90E−01 
               
               
                 LUSC Tumor Subtype 
                 9.99E−08 
                 1.80E−06 
               
               
                 COPD 
                 1.62E−01 
                 9.38E−03 
               
               
                 Genomic Smoking Status 
                 2.71E−09 
                 2.72E−04 
               
               
                 Subject 
                 9.66E−05 
                 5.87E−03 
               
               
                 Subject/Time 
                 6.96E−04 
                 1.40E−02 
               
               
                 Histology 
                 6.75E−03 
                 9.99E−08 
               
               
                 Location 
                 2.57E−02 
                 6.69E−01 
               
               
                 Subject/Location 
                 6.01E−02 
                 1.95E−01 
               
               
                 Asbestos Exposure 
                 1.23E−01 
                 7.47E−02 
               
               
                 Lung Cancer History 
                 1.32E−01 
                 9.92E−01 
               
               
                 Progression Status 
                 1.60E−01 
                 1.67E−05 
               
               
                 High-risk Job 
                 4.31E−01 
                 8.30E−01 
               
               
                 Sex 
                 5.62E−01 
                 8.90E−01 
               
               
                 LUSC Tumor Subtype 
                 9.99E−08 
                 1.80E−06 
               
               
                 COPD Status 
                 1.62E−01 
                 9.38E−03 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Statistical associations between Progression/Persistence versus 
               
               
                 Regression within each Molecular Subtype and Cohort (DC and 
               
               
                 VC) for each Gene Module. P-values less than 0.05 are reported. 
               
               
                 ns = not significant and N/A = not enough samples 
               
               
                 in each group to conduct the analysis. For molecular subtype, 
               
               
                 N = normal, S = secretory, I = inflammatory, and P = proflierative 
               
            
           
           
               
               
            
               
                   
                 Molecular Subtype 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 N 
                 N 
                 S 
                 S 
                 I 
                 I 
                 P 
                 P 
               
            
           
           
               
               
            
               
                   
                 Cohort 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 DC 
                 VC 
                 DC 
                 VC 
                 DC 
                 VC 
                 DC 
                 VC 
               
            
           
           
               
               
            
               
                   
                 Number of Progressive/Persistent Lesions 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 5 
                 1 
                 17 
                 7 
                 7 
                 5 
                 15 
                 7 
               
            
           
           
               
               
            
               
                 Module 
                 Number of Regressive Lesions 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Number 
                 3 
                 3 
                 8 
                 1 
                 4 
                 1 
                 15 
                 13 
               
               
                   
               
               
                 1 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 2 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 3 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 0.047  
                 ns 
               
               
                 4 
                 0.026 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 5 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 6 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 7 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 8 
                 0.027 
                 N/A 
                 ns 
                 N/A 
                 0.005 
                 N/A 
                 ns 
                 ns 
               
               
                 9 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 0.0017 
                 0.03 
               
               
                 1 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 2 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 3 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 0.047  
                 ns 
               
               
                 4 
                 0.026 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 5 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 6 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 7 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 ns 
               
               
                 8 
                 0.027 
                 N/A 
                 ns 
                 N/A 
                 0.005 
                 N/A 
                 ns 
                 ns 
               
               
                 9 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 ns 
                 N/A 
                 0.0017 
                 0.03 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Lung sites where Endobronchial Biopsies were obtained. The site  
               
               
                 code, name, and description are reported for each site. 
               
            
           
           
               
               
               
            
               
                 ID 
                 Name 
                 Description 
               
               
                   
               
               
                 096 
                 VC 
                 True Vocal Cords, Neck 
               
               
                 051 
                 Mouth 
                 Floor of Mouth 
               
               
                 007 
                 EPIG 
                 Epiglottis 
               
               
                 005 
                 ART 
                 Arytenoids 
               
               
                 008 
                 FVC 
                 False Vocal Cords 
               
               
                 095 
                 TR 
                 Trachea 
               
               
                 050 
                 MC 
                 Main Carina, Carina NOS 
               
               
                 086 
                 RMB 
                 Right Main Bronchus, incl Secondary Carina right 
               
               
                 091 
                 RUL 
                 Right Upper Lobe 
               
               
                 093 
                 RULO 
                 Right Upper Lobe Orifice or opening 
               
               
                 094 
                 RULS 
                 Right Upper Lobe Stump 
               
               
                 092 
                 RULB 
                 Right Upper Lobe Bronchus 
               
               
                 087 
                 RML 
                 Right Middle Lobe 
               
               
                 089 
                 RMLO 
                 Right Middle Lobe Orifice or opening 
               
               
                 090 
                 RMLS 
                 Right Middle Lobe Stump 
               
               
                 088 
                 RMLB 
                 Right Middle Lobe Bronchus 
               
               
                 082 
                 RLL 
                 Right Lower Lobe 
               
               
                 084 
                 RLLO 
                 Right Lower Lobe Orifice 
               
               
                 085 
                 RLLS 
                 Right Lower Lobe Stump 
               
               
                 083 
                 RLLB 
                 Right Lower Lobe Bronchus 
               
               
                 006 
                 BI 
                 Bronchus Intermedius 
               
               
                 052 
                 RB1 
                 RUL Apical Segment (AS) 
               
               
                 060 
                 RB2 
                 RUL Posterior Segment (PS) 
               
               
                 063 
                 RB3 
                 RUL Anterior Segment (ANTS) 
               
               
                 053 
                 RB1/2 
                 RUL Carina between RB1 and RB2 
               
               
                 054 
                 RB1/3 
                 RUL Carina between RB1 and RB3 
               
               
                 061 
                 RB2/3 
                 RUL Carina between RB2 and RB3 
               
               
                 059 
                 RB1A/B 
                 RUL AS Carina between RB1 A and B 
               
               
                 062 
                 RB2A/B 
                 RUL PS Carina between RB2 A and B 
               
               
                 064 
                 RB3A/B 
                 RUL ANTS Carina between RB3 A and B 
               
               
                 065 
                 RB4 
                 RML Lateral Segment (LS) 
               
               
                 068 
                 RB5 
                 RML Medial Segment (MS) 
               
               
                 066 
                 RB4/5 
                 RML LS Carina between RB4 and RB5 
               
               
                 067 
                 RB4A/B 
                 RML LS Carina between RB4 A and B 
               
               
                 069 
                 RB5A/B 
                 RML MS Carina between RB5 A and B 
               
               
                 070 
                 RB6 
                 RLL Superior Basal Segment (SBS) 
               
               
                 071 
                 RB6A/B 
                 RLL SBS Carina between RB6A and B 
               
               
                 072 
                 RB6A/C 
                 RLL SBS Carina between RB6A and C 
               
               
                 073 
                 RB6B/C 
                 RLL SBS Carina between RB6B and C 
               
               
                 074 
                 RB7 
                 RLL Medial Basal Segment (MBS) 
               
               
                 075 
                 RB7A/B 
                 RLL MBS Carina between RB7A and B 
               
               
                 076 
                 RB8 
                 RLL Anterior Basal Seg (ABS) 
               
               
                 077 
                 RB8/9 
                 RLL ABS Carina between RB8 and RB9 
               
               
                 078 
                 RB8A/B 
                 RLL ABS Carina between RB8A and B 
               
               
                 079 
                 RB9 
                 RLL Lateral Basal Segment (LBS) 
               
               
                 080 
                 RB9/10 
                 RLL LBS Carina between RB9 and RB10 
               
               
                 081 
                 RB9A/B 
                 RLL LBS Carina between RB9A and B 
               
               
                 055 
                 RB10 
                 RLL Posterior Basal Segment (PBS) 
               
               
                 056 
                 RB10A/B 
                 RLL PBS Carina between RB10A and B 
               
               
                 057 
                 RB10A/C 
                 RLL PBS Carina between RB10A and C 
               
               
                 058 
                 RB10B/C 
                 RLL PBS Carina between RB10B and C 
               
               
                 001 
                 666 
                 Location was surgically altered or removed 
               
               
                 002 
                 777 
                 Abstractor needs clinician help to code 
               
               
                 003 
                 888 
                 Location code is unknown, illegible 
               
               
                 004 
                 999 
                 Location code is blank, not noted 
               
               
                 043 
                 LMB 
                 Left Main Bronchus, incl Secondary Carina left 
               
               
                 044 
                 LMBD 
                 Left Main Bronchus, Distal 
               
               
                 046 
                 LUL 
                 Left Upper Lobe 
               
               
                 048 
                 LULO 
                 Left Upper Lobe Orifice or opening 
               
               
                 049 
                 LULS 
                 Left Upper Lobe Stump 
               
               
                 035 
                 LGL 
                 Lingula 
               
               
                 037 
                 LGLO 
                 Lingula Orifice or opening 
               
               
                 038 
                 LGLS 
                 Lingula Stump 
               
               
                 047 
                 LULB 
                 Left Upper Lobe Bronchus 
               
               
                 045 
                 LUDB 
                 Left Upper Division Bronchus 
               
               
                 036 
                 LGLDB 
                 Lingular Division Bronchus, lingular bronchus 
               
               
                 039 
                 LLL 
                 Left Lower Lobe 
               
               
                 041 
                 LLLO 
                 Left Lower Lobe Orifice or opening 
               
               
                 042 
                 LLLS 
                 Left Lower Lobe Stump 
               
               
                 040 
                 LLLB 
                 Left Lower Lobe Bronchus 
               
               
                 009 
                 LB1 + 2 
                 LUL Apical-Posterior Segment (APS) 
               
               
                 018 
                 LB3 
                 LUL Anterior Segment 
               
               
                 011 
                 LB1/2 
                 LUL APS Carina between LB1 and LB2 
               
               
                 010 
                 LB1 + 2/3 
                 LUL APS Carina between LB1 + 2 and LB3 
               
               
                 016 
                 LB2A/C 
                 LUL APS Carina between LB2 A and C 
               
               
                 017 
                 LB2B/C 
                 LUL APS Carina between LB2B and C 
               
               
                 019 
                 LB3A/B 
                 LUL ANTS Carina between LB3A and B 
               
               
                 020 
                 LB4 
                 LUL Superior Lingular Segment (SLS) 
               
               
                 023 
                 LB5 
                 LUL Inferior Lingular Segment (ILS) 
               
               
                 021 
                 LB4/5 
                 LUL SLS Carina between LB4 and LB5 
               
               
                 022 
                 LB4A/B 
                 LUL SLS Carina between LB4A and B 
               
               
                 024 
                 LB5A/B 
                 LUL ILS Carina between LB5A and B 
               
               
                 025 
                 LB6 
                 LLL Superior Segment (SS) 
               
               
                 026 
                 LB6A/B 
                 LLL SS Carina between LB6A and B 
               
               
                 027 
                 LB6A/C 
                 LLL SS Carina between LB6A and C 
               
               
                 028 
                 LB6B/C 
                 LLL SS Carina between LB6B and C 
               
               
                 029 
                 LB8 
                 LLL Antero Medial Basal Segment (AMBS) 
               
               
                 030 
                 LB8/9 
                 LLL AMBS Carina between LB8 and LB9 
               
               
                 031 
                 LB8A/B 
                 LLL AMBS Carina between LB8A and B 
               
               
                 032 
                 LB9 
                 LLL Lateral Basal Segment (LBS) 
               
               
                 033 
                 LB9/10 
                 LLL LBS Carina between LB9 and LB 10 
               
               
                 034 
                 LB9A/B 
                 LLL LBS Carina between LB9A and B 
               
               
                 012 
                 LB10 
                 LLL Posterior Basal Segment (PBS) 
               
               
                 013 
                 LB10A/B 
                 LLL PBS Carina between LB10A and B 
               
               
                 014 
                 LB10A/C 
                 LLL PBS Carina between LB10A and C 
               
               
                 015 
                 LB10B/C 
                 LLL PBS Carina between LB10B and C 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Antibodies used in the Immunofluorescence Studies. 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 Antigen 
                   
               
               
                 Antibody 
                 Company 
                 Catalog 
                 Dilution 
                 retrival 
                 Species 
               
               
                   
               
            
           
           
               
            
               
                 Immune cell type markers 
               
            
           
           
               
               
               
               
               
               
            
               
                 CD68 
                 Dako 
                 m0876 
                 1- 
                 AR6 
                 mous 
               
               
                 CD163 
                 Cell Marque 
                 163m-16 
                 1-100 
                 AR9 
                 mous 
               
               
                 CD4 
                 Thermo Fisher 
                 ms1528S 
                 1-100 
                 AR9 
                 mous 
               
               
                 CD8 
                 Dako 
                 M7103 
                 1-100 
                 AR9 
                 mous 
               
            
           
           
               
            
               
                 Epithelial cell type and proliferation markers 
               
            
           
           
               
               
               
               
               
               
            
               
                 Ac-α-Tub 
                 Sigma 
                 T6793 
                 1-100 
                 citrat 
                 mous 
               
               
                 KRT5 
                 BioLegend 
                 905-901 
                 1-100 
                 citrat 
                 chicken 
               
               
                 KI67 
                 Abeam 
                 ab16667 
                 1-100 
                 citrat 
                 rabbit 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 Genomic smoking status over time by subject. The smoking status of  
               
               
                 each subject at each time point was computed based on a  previously published smoking-associated gene 
               
               
                 signature 6  (see methods for details). The rows indicate the  smoking status across all time points sampled 
               
               
                 for each patient. The −&gt; symbol indicates changes in  smoking status over time. There is not a statistical 
               
               
                 difference between the distribution of subjects in the  smoking status categories between the discovery and 
               
               
                 validation cohorts by a two-sided Fisher&#39;s exact Test (p = 0.90).  
               
               
                 Source data are provided as a Source Data file. 
               
            
           
           
               
               
               
            
               
                   
                 Discovery Cohort 
                 Validation Cohort 
               
               
                 Genomic smoking  status over time 
                 Number  of Subjects  
                 Number  of Subjects 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Current 
                 9 
                 9 
               
               
                 Former 
                 10 
                 5 
               
               
                 Current-&gt;Former 
                 7 
                 4 
               
               
                 F ormer-&gt;Current 
                 3 
                 2 
               
               
                 Current-&gt;Former-&gt;Current 
                 1 
                 0 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12 
               
             
            
               
                   
               
               
                 Molecular Subtype associations with previous history of lung cancer. Previous history of lung 
               
               
                 cancer (LC) was categorized as follows: no history (No LC History), a previous history of LC 
               
               
                 that include a lung squamous cell carcinoma (LC History - LUSC), and a previous history of LC 
               
               
                 that does not include a lung squamous cell carcinoma (LC History - Other). Statistical tests 
               
               
                 within the discovery and validation cohorts were performed using two-sided Fisher&#39;s exact tests. 
               
            
           
           
               
               
               
            
               
                   
                 Discovery Cohort Biopsies (n = 190) 
                 Validation Cohort Biopsies (n = 105) 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 No LC 
                 LC History - 
                 LC History - 
                   
                 No LC 
                 LC History - 
                 LC History - 
                   
               
               
                 Variable 
                 History 
                 LUSC 
                 Other 
                 P-Value 
                 History 
                 LUSC 
                 Other 
                 P-Value 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Molecular Subtype 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Proliferative 
                 14 
                 5 
                 33 
                   
                 12 
                 9 
                 7 
               
               
                 Inflammatory 
                 10 
                 6 
                 21 
                   
                 12 
                 4 
                 14 
               
               
                 Secretory 
                 26 
                 8 
                 27 
                   
                 14 
                 13 
                 7 
               
               
                 Normal-like 
                 9 
                 3 
                 28 
                 p = 0.19 
                 6 
                 1 
                 6 
                 p = 0.10