Patent Publication Number: US-2021193267-A1

Title: Methods, systems, and related computer program products for evaluating cancer model fidelity

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to, and the benefit of, U.S. Provisional Patent Application No. 62/949,295 entitled “METHODS, SYSTEMS, AND RELATED COMPUTER PROGRAM PRODUCTS FOR EVALUATING CANCER MODEL FIDELITY” filed Dec. 17, 2019, the disclosure of which is hereby incorporated by reference in its entirety. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     This invention was made with government support under grant number CA228991 awarded by the National Institutes of Health. The government has certain rights in the invention. 
    
    
     BACKGROUND 
     Models are widely used to investigate cancer biology and to identify potential therapeutics. Popular modeling modalities are cancer cell lines (CCLs), genetically engineered mouse models (GEMMs), and patient derived xenografts (PDXs). These classes of models differ in the types of questions that they are designed to address. CCLs are often used to address cell intrinsic mechanistic questions, GEMMs to chart progression of molecularly defined-disease, and PDXs to explore patient-specific response to therapy in a physiologically relevant context. Models also differ in the extent to which they represent specific aspects of a cancer type. Even with this intra- and inter-class model variation, all models should represent the tumor type or sub-type under investigation, and not another type of tumor, and not a non-cancerous tissue. Therefore, cancer-models should be selected not only based on the specific biological question but also based on the similarity of the model to the cancer type under investigation (Mouradov et al. (2014) “Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer,” Cancer Research, 74(12):3238-3247; Stuckelberger et al. (2018) “Precious GEMMs: emergence of faithful models for ovarian cancer research,” The Journal of Pathology, 245(2):129-131). 
     Various methods have been proposed to determine the similarity of cancer models to their intended subjects. Domcke et al. devised a ‘suitability score’ as a metric of the molecular similarity of CCLs to high grade serous ovarian carcinoma based on a heuristic weighting of copy number alterations, mutation status of several genes that distinguish ovarian cancer subtypes, and hypermutation status (Domcke et al. (2013) “Evaluating cell lines as tumour models by comparison of genomic profiles,” Nature Communications, 4:2126). Other studies have taken analogous approaches by either focusing on transcriptomic or ensemble molecular profiles (e.g. transcriptomic and copy number alterations) to quantify the similarity of cell lines to tumors (Jiang et al. (2016) “Comprehensive comparison of molecular portraits between cell lines and tumors in breast cancer,” BMC Genomics 17 Suppl 7:525; Chen (2015) “Relating hepatocellular carcinoma tumor samples and cell lines using gene expression data in translational research,” BMC Medical Genomics 8 Suppl 2:S5.; Vincent et al. (2015) “Assessing breast cancer cell lines as tumour models by comparison of mRNA expression profiles,” Breast Cancer Research 17:114). These studies were tumor-type specific, focusing on CCLs that model, for example, hepatocellular carcinoma or breast cancer. More recently, Yu et al. compared the transcriptomes of CCLs to The Cancer Genome Atlas (TCGA) by correlation analysis, resulting in a panel of CCLs recommended as most representative of 22 tumor types (Yu et al. (2019) “Comprehensive transcriptomic analysis of cell lines as models of primary tumors across 22 tumor types,” Nature Communications 10(1):3574). While all of these studies have provided valuable information, they leave at least two major challenges unmet. The first challenge is to determine the fidelity of GEMMs and PDXs and whether there are stark differences between these classes of models and CCLs. The other major unmet challenge is to allow for rapid assessment of new, emerging cancer models. This challenge is especially relevant now as technical barriers to model generation have been substantially lowered, and because each PDX can be considered a distinct entity requiring validation. 
     SUMMARY 
     The present disclosure relates, in certain aspects, to a computational software tool, called CancerCellNet (CCN), which can be used for several purposes in the clinical and research settings of cancer. A function of the tool is to classify biological samples according to their similarity to over two dozen well-defined cancer tumor types (e.g. breast invasive carcinoma), and sub-types thereof (e.g. ‘luminal A’). This tool is especially useful in cases where the tumor type is difficult for pathologists to determine, such as when the cancer has metastasized and the origin of the primary tumor is unknown. The tool is also useful as a means to gauge the similarity of cancers models to naturally occurring disease. Researchers will be able to use CancerCellNet to determine the model that is most appropriate for their research or translational question. 
     CancerCellNet uses various types of data, including gene expression or transcriptomic data in certain applications. In some embodiments, the software uses the Random Forest machine learning classification technique. In certain of these embodiments, the training data used to train the algorithm are derived from The Cancer Genome Atlas (TCGA) and/or other data sources. As described herein, CancerCellNet&#39;s performance has been assessed on both held out TCGA data, as well as a host of well-annotated tumor data from other sources. The methods and related aspects of the present disclosure also provide a way to transform the data that enables CancerCellNet to be ‘agnostic’ with regards to the type of transcriptomic or other data types. Therefore, the methods are not limited to either microarray data, or RNA-Seq data. In addition, the present disclosure also provides a means of quickly identifying relevant features, which shortens the classifier training time, and makes classification rapid. 
     In certain aspects, the present disclosure provides a method of generating a training classifier at least partially using a computer. The method includes generating, by the computer, one or more training data sets, wherein a given training data set comprises gene expression profiles of subjects having a given tumor type. The method also includes identifying, by the computer, intersecting genes between the training data sets and one or more query samples to produce one or more intersecting gene sets, and partitioning, by the computer, the intersecting gene sets into training subsets and validation subsets for a given tumor type. The method also includes identifying, by the computer, one or more groups of differentially over-expressed genes, differentially under-expressed genes, and/or least differentially expressed genes in the training subsets to produce one or more baseline gene sets, and generating, by the computer, one or more gene-pairs for one or more of the tumor types from the baseline gene sets. The method also includes pair-transforming, by the computer, the gene-pairs to produce one or more binarized training data sets, and selecting, by the computer, one or more discriminatory gene-pairs for at least some of the tumor types. In addition, the method also includes generating, by the computer, one or more random gene-pair profiles through random permutations of the training data sets, which gene-pair profiles lack tumor type annotation, and selecting, by the computer, one or more of the gene-pairs as features to produce a random forest classifier, thereby generating the training classifier. 
     In other aspects, the present disclosure provides a method of evaluating a cancer model at least partially using a computer. The method includes generating, by the computer, one or more training data sets, wherein a given training data set comprises gene expression profiles of subjects having a given tumor type, and identifying, by the computer, intersecting genes between the training data sets and one or more query samples to produce one or more intersecting gene sets. The method also includes partitioning, by the computer, the intersecting gene sets into training subsets and validation subsets for a given tumor type, and identifying, by the computer, one or more groups of differentially over-expressed genes, differentially under-expressed genes, and/or least differentially expressed genes in the training subsets to produce one or more baseline gene sets. The method also includes generating, by the computer, one or more gene-pairs for one or more of the tumor types from the baseline gene sets, and pair-transforming, by the computer, the gene-pairs to produce one or more binarized training data sets. The method also includes selecting, by the computer, one or more discriminatory gene-pairs for at least some of the tumor types, and generating, by the computer, one or more random gene-pair profiles through random permutations of the training data sets, which gene-pair profiles lack tumor type annotation. In addition, the method also includes selecting, by the computer, one or more of the gene-pairs as features to produce a random forest classifier, and evaluating one or more cancer models using the random forest classifier. 
     In some embodiments of the methods, the query samples comprise cancer cell line (CCL) samples, patient derived xenograft (PDX) samples, and/or genetically engineered mouse model (GEMM) samples, or data derived from such sample types. In certain embodiments, the partitioning step comprises randomly sampling the gene expression profiles for the given tumor type. In some embodiments, the methods include down-sampling, up-sampling, and/or log transforming one or more of the training subsets. In certain embodiments, the methods include using log transformed down-sampled counts to produce the baseline gene sets. In some embodiments, the methods include stratifying sampling when selecting gene-pairs as features to produce the random forest classifier. In certain embodiments, the methods include validating the training classifier using the validation subsets. In some embodiments, the methods include pair-transforming the validation subsets. 
     In some embodiments, the methods include evaluating performance of the training classifier using precision-recall curve and area under the precision-recall curve (AUPR). In certain embodiments, the methods include repeating one or more steps of generating the training classifier. In some embodiments, the methods include using gene-pairs selected from genes listed in Table 1. In certain embodiments, the methods include adding one or more additional features to produce the random forest classifier. In some embodiments, the methods include evaluating one or more cancer cell line (CCL) expression profiles, patient derived xenograft (PDX) expression profiles, and/or genetically engineered mouse model (GEMM) expression profiles using the training classifier. In some embodiments of the methods, the gene-pairs comprise genes from different species. 
     In certain embodiments of the methods, gene expression profiles comprise RNA-seq and/or microarray gene expression profiles. In some embodiments, the methods also include generating one or more tumor sub-type classifiers. In certain embodiments, the tumor sub-type classifiers comprise one or more gene pairs selected from genes listed in Tables 2-12. 
     In other aspects, the present disclosure provides a system, comprising a controller comprising, or capable of accessing, computer readable media comprising non-transitory computer executable instruction which, when executed by at least electronic processor perform at least: generating one or more training data sets, wherein a given training data set comprises gene expression profiles of subjects having a given tumor type, and identifying intersecting genes between the training data sets and one or more query samples to produce one or more intersecting gene sets. The electronic processor also performs partitioning the intersecting gene sets into training subsets and validation subsets for a given tumor type, and identifying one or more groups of differentially over-expressed genes, differentially under-expressed genes, and/or least differentially expressed genes in the training subsets to produce one or more baseline gene sets. The electronic processor also performs generating one or more gene-pairs for one or more of the tumor types from the baseline gene sets, and pair-transforming the gene-pairs to produce one or more binarized training data sets. The electronic processor also performs selecting one or more discriminatory gene-pairs for at least some of the tumor types, and generating one or more random gene-pair profiles through random permutations of the training data sets, which gene-pair profiles lack tumor type annotation. In addition, the electronic processor also performs selecting one or more of the gene-pairs as features to produce a random forest classifier, thereby generating the training classifier. 
     In other aspects, the present disclosure also provides a computer readable media comprising non-transitory computer executable instruction which, when executed by at least electronic processor perform at least: generating one or more training data sets, wherein a given training data set comprises gene expression profiles of subjects having a given tumor type, and identifying intersecting genes between the training data sets and one or more query samples to produce one or more intersecting gene sets. The electronic processor also performs partitioning the intersecting gene sets into training subsets and validation subsets for a given tumor type, and identifying one or more groups of differentially over-expressed genes, differentially under-expressed genes, and/or least differentially expressed genes in the training subsets to produce one or more baseline gene sets. The electronic processor also performs generating one or more gene-pairs for one or more of the tumor types from the baseline gene sets, and pair-transforming the gene-pairs to produce one or more binarized training data sets. The electronic processor also performs selecting one or more discriminatory gene-pairs for at least some of the tumor types, and generating one or more random gene-pair profiles through random permutations of the training data sets, which gene-pair profiles lack tumor type annotation. In addition, the electronic processor also performs selecting one or more of the gene-pairs as features to produce a random forest classifier, thereby generating the training classifier. 
     In some embodiments of the systems or computer readable media, the query samples comprise cancer cell line (CCL) samples, patient derived xenograft (PDX) samples, and/or genetically engineered mouse model (GEMM) samples. In certain embodiments of the systems or computer readable media, the partitioning step comprises randomly sampling the gene expression profiles for the given tumor type. In some embodiments, the systems or computer readable media include down-sampling, up-sampling, and/or log transforming one or more of the training subsets. In some embodiments, the systems or computer readable media include using log transformed down-sampled counts to produce the baseline gene sets. In some embodiments, the systems or computer readable media include stratifying sampling when selecting gene-pairs as features to produce the random forest classifier. In some embodiments, the systems or computer readable media include validating the training classifier using the validation subsets. In some embodiments, the systems or computer readable media include pair-transforming the validation subsets. In some embodiments, the systems or computer readable media include evaluating performance of the training classifier using precision-recall curve and area under the precision-recall curve (AUPR). In some embodiments, the systems or computer readable media include repeating one or more steps of generating the training classifier. 
     In some embodiments of the systems or computer readable media, the gene-pairs are selected from genes listed in Table 1. In some embodiments, the systems or computer readable media include adding one or more additional features to produce the random forest classifier. In some embodiments, the systems or computer readable media include evaluating one or more cancer cell line (CCL) expression profiles, patient derived xenograft (PDX) expression profiles, and/or genetically engineered mouse model (GEMM) expression profiles using the training classifier. In some embodiments of the systems or computer readable media, the gene-pairs comprise genes from different species. In some embodiments of the systems or computer readable media, the gene expression profiles comprise RNA-seq and/or microarray gene expression profiles. In some embodiments, the systems or computer readable media further include generating one or more tumor sub-type classifiers. In some embodiments of the systems or computer readable media, the tumor sub-type classifiers comprise one or more gene pairs selected from genes listed in Tables 2-12. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate certain embodiments, and together with the written description, serve to explain certain principles of the methods, systems, and related computer readable media disclosed herein. The description provided herein is better understood when read in conjunction with the accompanying drawings which are included by way of example and not by way of limitation. It will be understood that like reference numerals identify like components throughout the drawings, unless the context indicates otherwise. It will also be understood that some or all of the figures may be schematic representations for purposes of illustration and do not necessarily depict the actual relative sizes or locations of the elements shown. 
         FIG. 1  is a flow chart that schematically depicts exemplary method steps according to some aspects disclosed herein. 
         FIG. 2  is a schematic diagram of an exemplary system suitable for use with certain aspects disclosed herein. 
         FIG. 3A  schematically depicts exemplary method steps according to some aspects disclosed herein. 
         FIG. 3B  is a plot of mean area under the precision-recall curve (AUPR) (y-axis) for various cancer types (x-axis). 
         FIG. 4A  are plots showing the performance of a classifier according to certain embodiments disclosed herein for various cancer types in which precision is represented on the y-axis, while recall is represented on the x-axis. 
         FIG. 4B  is a plot of AUPR (y-axis) for various cancer types (x-axis). 
         FIG. 4C  is a plot of AUPR of Cross-Species Testing Data with AUPR represented on the y-axis for various cell types represented on the x-axis. 
         FIG. 4D  schematically depicts exemplary method steps according to some aspects disclosed herein. 
         FIG. 4E  is a plot of cancer subtypes (y-axis) versus mean AUPR (x-axis). 
         FIG. 5A  is a plot of RNA-seq expression data of 657 different cell lines mined across 20 cancer types. 
         FIG. 5B  is a plot of CCN profiles. 
         FIG. 5C  is a plot of classifications. 
         FIG. 5D  is a plot of sub-type classification of Lung Squamous Cell Carcinoma (LUSC) cell lines. 
         FIG. 5E  is a plot of sub-type classification of Lung Adenocarcinoma (LUAD) cell lines. 
         FIG. 5F  is a plot of normalized citation count (y-axis) versus general classification score (x-axis). 
         FIG. 6A  is a plot of AUPR of Microarray Testing Data with AUPR represented on the y-axis for various cancer types represented on the x-axis. 
         FIG. 6B  is a plot of microarray expression data for cancer cell lines mined across various cancer types. 
         FIG. 6C  are plots comparing CCLE classification scores between microarray (y-axis) and RNA-seq data (x-axis). 
         FIG. 7A  is a plot of expression data mined across various cancer types. 
         FIG. 7B  is a plot of CCN profiles. 
         FIG. 7C  is a plot of classifications. 
         FIG. 7D  is a plot of classifications. 
         FIG. 7E  is a plot of classifications. 
         FIG. 8A  is a plot of expression data mined across various cancer types. 
         FIG. 8B  is a plot of CCN profiles. 
         FIG. 8C  is a plot of classifications. 
         FIG. 8D  is a plot of classifications. 
         FIG. 9  is a plot of classifications. 
         FIG. 10  are plots of general CCN scores of cancer models compared on a per tumor type basis. 
         FIG. 11  are plots of sub-type classifications. 
     
    
    
     DEFINITIONS 
     In order for the present disclosure to be more readily understood, certain terms are first defined below. Additional definitions for the following terms and other terms may be set forth through the specification. If a definition of a term set forth below is inconsistent with a definition in an application or patent that is incorporated by reference, the definition set forth in this application should be used to understand the meaning of the term. 
     As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, a reference to “a method” includes one or more methods, and/or steps of the type described herein and/or which will become apparent to those persons skilled in the art upon reading this disclosure and so forth. 
     It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. Further, unless defined otherwise, 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 disclosure pertains. In describing and claiming the methods, systems, and component parts, the following terminology, and grammatical variants thereof, will be used in accordance with the definitions set forth below. 
     About: As used herein, “about” or “approximately” as applied to one or more values or elements of interest, refers to a value or element that is similar to a stated reference value or element. In certain embodiments, the term “about” or “approximately” refers to a range of values or elements that falls within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value or element unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value or element). 
     Cancer Type: As used herein, “cancer type” or “tumor type” refers to type or subtype of cancer defined, e.g., by histopathology. Cancer type can be defined by any conventional criterion, such as on the basis of occurrence in a given tissue (e.g., blood cancers, CNS, brain cancers, lung cancers (small cell and non-small cell), skin cancers, nose cancers, throat cancers, liver cancers, bone cancers, lymphomas, pancreatic cancers, bowel cancers, rectal cancers, thyroid cancers, bladder cancers, kidney cancers, mouth cancers, stomach cancers, breast cancers, prostate cancers, ovarian cancers, lung cancers, intestine cancers, soft tissue cancers, thyroid cancers, neuroendocrine cancers, gastroesophageal cancers, head and neck cancers, gynecological cancers, colorectal cancers, urothelial cancers, solid state cancers, heterogeneous cancers, homogenous cancers), unknown primary origin and the like, and/or of the same cell lineage (e.g., carcinoma, sarcoma, lymphoma, cholangiocarcinoma, leukemia, mesothelioma, melanoma, or glioblastoma) and/or cancer markers, such as Her2, CA15-3, CA19-9, CA-125, CEA, AFP, PSA, HCG, hormone receptor and NMP-22. Cancers can also be classified by stage (e.g., stage 1, 2, 3, or 4) and whether of primary or secondary origin. 
     Classifier: As used herein, “classifier,” generally refers to algorithm computer code that receives, as input, test data and produces, as output, a classification of the input data as belonging to one or another class. 
     Machine Learning Algorithm: As used herein, “machine learning algorithm,” generally refers to an algorithm, executed by computer, that automates analytical model building, e.g., for clustering, classification or pattern recognition. Machine learning algorithms may be supervised or unsupervised. Learning algorithms include, for example, artificial neural networks (e.g., back propagation networks), discriminant analyses (e.g., Bayesian classifier or Fischer analysis), support vector machines, decision trees (e.g., recursive partitioning processes such as CART—classification and regression trees, or random forests), linear classifiers (e.g., multiple linear regression (MLR), partial least squares (PLS) regression, and principal components regression), hierarchical clustering, and cluster analysis. A dataset on which a machine learning algorithm learns can be referred to as “training data.” 
     Sample: As used herein, “sample” means anything capable of being analyzed by the methods and/or systems disclosed herein. 
     Subject: As used herein, “subject” refers to an animal, such as a mammalian species (e.g., human) or avian (e.g., bird) species. More specifically, a subject can be a vertebrate, e.g., a mammal such as a mouse, a primate, a simian or a human. Animals include farm animals (e.g., production cattle, dairy cattle, poultry, horses, pigs, and the like), sport animals, and companion animals (e.g., pets or support animals). A subject can be a healthy individual, an individual that has or is suspected of having a disease or a predisposition to the disease, or an individual that is in need of therapy or suspected of needing therapy. The terms “individual” or “patient” are intended to be interchangeable with “subject.” For example, a subject can be an individual who has been diagnosed with having a cancer, is going to receive a cancer therapy, and/or has received at least one cancer therapy. The subject can be in remission of a cancer. 
     DETAILED DESCRIPTION 
     Cancer researchers use, for example, cell lines, patient derived xenografts, and genetically engineered mice as models to investigate tumor biology and to identify therapeutics. The generalizability and power of a model derives from the fidelity with which it represents the tumor type of investigation, however, the extent to which this is true is often unclear. The preponderance of models and the ability to readily generate new ones has created a demand for tools that can measure the extent and ways in which cancer models resemble or diverge from native tumors. In certain aspects, the present disclosure relates to a computational tool, called CancerCellNet (CCN), which measures the similarity of cancer models, in some embodiments, to 25 naturally occurring tumor types and 46 sub-types, in a platform and species agnostic manner. As illustrated in the Examples provided herein, this tool was applied to 657 cancer cell lines, 415 patient derived xenografts, and 26 distinct genetically engineered mouse models, documenting the most faithful models, identifying cancers underserved by adequate models, and finding models with annotations that do not match their classification. By comparing models across modalities, the illustrative Examples further show that genetically engineered mice have higher transcriptional fidelity than patient derived xenografts and cell lines in four out of five tumor types. 
     Exemplary Methods 
     The present disclosure provides various methods of generating training classifiers and/or evaluating cancer models. To illustrate,  FIG. 1  is flow chart that schematically depicts exemplary method steps according to some aspects disclosed herein. As shown, method  100  includes generating training data sets in which a given training data set includes gene expression profiles of subjects having a given tumor type (step  102 ). Typically, one or more of the steps of method  100  are computer implemented. Exemplary systems and computers are described further herein. Method  100  also includes identifying intersecting genes between the training data sets and query samples to produce intersecting gene sets (step  104 ), and partitioning the intersecting gene sets into training subsets and validation subsets for a given tumor type (step  106 ). Method  100  also includes identifying groups of differentially over-expressed genes, differentially under-expressed genes, and/or least differentially expressed genes in the training subsets to produce baseline gene sets (step  108 ), and generating gene-pairs for the tumor types from the baseline gene sets (step  110 ). Method  100  also includes pair-transforming the gene-pairs to produce binarized training data sets (step  112 ), and selecting discriminatory gene-pairs for at least some of the tumor types (step  114 ). In addition, method  100  also includes generating random gene-pair profiles through random permutations of the training data sets (step  116 ). Typically, these gene-pair profiles lack tumor type annotation. Method  100  also includes selecting gene-pairs as features to produce a random forest classifier to generate the training classifier (step  118 ). Typically, the methods disclosed herein include evaluating cancer models using the random forest classifier using the training classifier generated by method  100 . Aspects of the methods are described further herein, including in the Example. 
     In some embodiments of the methods, the query samples comprise cancer cell line (CCL) samples, patient derived xenograft (PDX) samples, and/or genetically engineered mouse model (GEMM) samples. In certain embodiments, the partitioning step comprises randomly sampling the gene expression profiles for the given tumor type. In some embodiments, the methods include down-sampling, up-sampling, and/or log transforming one or more of the training subsets. In certain embodiments, the methods include using log transformed down-sampled counts to produce the baseline gene sets. In some embodiments, the methods include stratifying sampling when selecting gene-pairs as features to produce the random forest classifier. In certain embodiments, the methods include validating the training classifier using the validation subsets. In some embodiments, the methods include pair-transforming the validation subsets. 
     In some embodiments, the methods include evaluating performance of the training classifier using precision-recall curve and area under the precision-recall curve (AUPR). In certain embodiments, the methods include repeating one or more steps of generating the training classifier. In some embodiments, the methods include the gene-pairs are selected from genes listed in Table 1. In certain embodiments, the methods include adding one or more additional features to produce the random forest classifier. In some embodiments, the methods include evaluating one or more cancer cell line (CCL) expression profiles, patient derived xenograft (PDX) expression profiles, and/or genetically engineered mouse model (GEMM) expression profiles using the training classifier. In some embodiments of the methods, the gene-pairs comprise genes from different species. 
     In certain embodiments of the methods, gene expression profiles comprise RNA-seq and/or microarray gene expression profiles. In some embodiments, the methods also include generating one or more tumor sub-type classifiers. In certain embodiments, the tumor sub-type classifiers comprise one or more gene pairs selected from genes listed in Tables 2-12. 
     Exemplary Systems and Computer Readable Media 
     The present disclosure also provides various systems and computer program products or machine readable media. In some aspects, for example, the methods described herein are optionally performed or facilitated at least in part using systems, distributed computing hardware and applications (e.g., cloud computing services), electronic communication networks, communication interfaces, computer program products, machine readable media, electronic storage media, software (e.g., machine-executable code or logic instructions) and/or the like. To illustrate,  FIG. 2  provides a schematic diagram of an exemplary system suitable for use with implementing at least aspects of the methods disclosed in this application. As shown, system  200  includes at least one controller or computer, e.g., server  202  (e.g., a search engine server), which includes processor  204  and memory, storage device, or memory component  206 , and one or more other communication devices  214  (e.g., client-side computer terminals, telephones, tablets, laptops, other mobile devices, etc.) positioned remote from and in communication with the remote server  202 , through electronic communication network  212 , such as the Internet or other internetwork. Communication device  214  typically includes an electronic display (e.g., an internet enabled computer or the like) in communication with, e.g., server  202  computer over network  212  in which the electronic display comprises a user interface (e.g., a graphical user interface (GUI), a web-based user interface, and/or the like) for displaying results upon implementing the methods described herein. In certain aspects, communication networks also encompass the physical transfer of data from one location to another, for example, using a hard drive, thumb drive, or other data storage mechanism. System  200  also includes program product  208  stored on a computer or machine readable medium, such as, for example, one or more of various types of memory, such as memory  206  of server  202 , that is readable by the server  202 , to facilitate, for example, a guided search application or other executable by one or more other communication devices, such as  214  (schematically shown as a desktop or personal computer). In some aspects, system  200  optionally also includes at least one database server, such as, for example, server  210  associated with an online website having data stored thereon (e.g., control sample or comparator result data, indexed customized therapies, etc.) searchable either directly or through search engine server  202 . System  200  optionally also includes one or more other servers positioned remotely from server  202 , each of which are optionally associated with one or more database servers  210  located remotely or located local to each of the other servers. The other servers can beneficially provide service to geographically remote users and enhance geographically distributed operations. 
     As understood by those of ordinary skill in the art, memory  206  of the server  202  optionally includes volatile and/or nonvolatile memory including, for example, RAM, ROM, and magnetic or optical disks, among others. It is also understood by those of ordinary skill in the art that although illustrated as a single server, the illustrated configuration of server  202  is given only by way of example and that other types of servers or computers configured according to various other methodologies or architectures can also be used. Server  202  shown schematically in  FIG. 2 , represents a server or server cluster or server farm and is not limited to any individual physical server. The server site may be deployed as a server farm or server cluster managed by a server hosting provider. The number of servers and their architecture and configuration may be increased based on usage, demand and capacity requirements for the system  200 . As also understood by those of ordinary skill in the art, other user communication device  214  in these aspects, for example, can be a laptop, desktop, tablet, personal digital assistant (PDA), cell phone, server, or other types of computers. As known and understood by those of ordinary skill in the art, network  212  can include an internet, intranet, a telecommunication network, an extranet, or world wide web of a plurality of computers/servers in communication with one or more other computers through a communication network, and/or portions of a local or other area network. 
     As further understood by those of ordinary skill in the art, exemplary program product or machine readable medium  208  is optionally in the form of microcode, programs, cloud computing format, routines, and/or symbolic languages that provide one or more sets of ordered operations that control the functioning of the hardware and direct its operation. Program product  208 , according to an exemplary aspect, also need not reside in its entirety in volatile memory, but can be selectively loaded, as necessary, according to various methodologies as known and understood by those of ordinary skill in the art. 
     As further understood by those of ordinary skill in the art, the term “computer-readable medium” or “machine-readable medium” refers to any medium that participates in providing instructions to a processor for execution. To illustrate, the term “computer-readable medium” or “machine-readable medium” encompasses distribution media, cloud computing formats, intermediate storage media, execution memory of a computer, and any other medium or device capable of storing program product  208  implementing the functionality or processes of various aspects of the present disclosure, for example, for reading by a computer. A “computer-readable medium” or “machine-readable medium” may take many forms, including but not limited to, non-volatile media, volatile media, and transmission media. Non-volatile media includes, for example, optical or magnetic disks. Volatile media includes dynamic memory, such as the main memory of a given system. Transmission media includes coaxial cables, copper wire and fiber optics, including the wires that comprise a bus. Transmission media can also take the form of acoustic or light waves, such as those generated during radio wave and infrared data communications, among others. Exemplary forms of computer-readable media include a floppy disk, a flexible disk, hard disk, magnetic tape, a flash drive, or any other magnetic medium, a CD-ROM, any other optical medium, punch cards, paper tape, any other physical medium with patterns of holes, a RAM, a PROM, and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave, or any other medium from which a computer can read. 
     Program product  208  is optionally copied from the computer-readable medium to a hard disk or a similar intermediate storage medium. When program product  208 , or portions thereof, are to be run, it is optionally loaded from their distribution medium, their intermediate storage medium, or the like into the execution memory of one or more computers, configuring the computer(s) to act in accordance with the functionality or method of various aspects. All such operations are well known to those of ordinary skill in the art of, for example, computer systems. 
     To further illustrate, in certain aspects, this application provides systems that include one or more processors, and one or more memory components in communication with the processor. The memory component typically includes one or more instructions that, when executed, cause the processor to provide information that causes at least one CCN model or component thereof, and/or the like to be displayed (e.g., via communication device  214  or the like) and/or receive information from other system components and/or from a system user (e.g., via communication device  214  or the like). 
     In some aspects, program product  208  includes non-transitory computer-executable instructions which, when executed by electronic processor  204  perform at least: generating one or more training data sets, wherein a given training data set comprises gene expression profiles of subjects having a given tumor type; identifying intersecting genes between the training data sets and one or more query samples to produce one or more intersecting gene sets; partitioning the intersecting gene sets into training subsets and validation subsets for a given tumor type; identifying one or more groups of differentially over-expressed genes, differentially under-expressed genes, and/or least differentially expressed genes in the training subsets to produce one or more baseline gene sets; generating one or more gene-pairs for one or more of the tumor types from the baseline gene sets; pair-transforming the gene-pairs to produce one or more binarized training data sets; selecting one or more discriminatory gene-pairs for at least some of the tumor types; generating one or more random gene-pair profiles through random permutations of the training data sets, which gene-pair profiles lack tumor type annotation; and selecting one or more of the gene-pairs as features to produce a random forest classifier, thereby generating the training classifier. 
     System  200  also typically includes additional system components that are configured to perform various aspects of the methods described herein. In some of these aspects, one or more of these additional system components are positioned remote from and in communication with the remote server  202  through electronic communication network  212 , whereas in other aspects, one or more of these additional system components are positioned local, and in communication with server  202  (i.e., in the absence of electronic communication network  212 ) or directly with, for example, desktop computer  214 . 
     Additional details relating to computer systems and networks, databases, and computer program products are also provided in, for example, Peterson,  Computer Networks: A Systems Approach , Morgan Kaufmann, 5th Ed. (2011), Kurose,  Computer Networking: A Top - Down Approach , Pearson, 7 th  Ed. (2016), Elmasri,  Fundamentals of Database Systems , Addison Wesley, 6th Ed. (2010), Coronel,  Database Systems: Design, Implementation , &amp;  Management , Cengage Learning, 11 th  Ed. (2014), Tucker,  Programming Languages , McGraw-Hill Science/Engineering/Math, 2nd Ed. (2006), and Rhoton,  Cloud Computing Architected: Solution Design Handbook , Recursive Press (2011), which are each incorporated by reference in their entirety. 
     Example 
     This example presents various exemplary aspects of CancerCellNet (CCN). Details of CCN are also described in Peng et al. “Evaluating the transcriptional fidelity of cancer models.” bioRxiv (2020) (10.1101/2020.03.27.012757), the entire disclosure of which, including all supplemental material, is incorporated by reference in its entirety. 
     Training Broad CancerCellNet 
     To generate training data sets, 9288 patient tumor non-normalized RNA-seq expression profiles and their corresponding sample tables annotating each patient profile to a cancer type across 25 different tumor types were downloaded from TCGA using TCGAWorkflowData, TCGAbiolinks (Silva et al. (2016) “TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages,” [version 2; peer review: 1 approved, 2 approved with reservations]. F1000Research 5:1542) and SummarizedExperiment (Morgan et al. (2018) SummarizedExperiment: SummarizedExperiment container) packages. After compiling the patient tumor dataset, the intersecting genes between TCGA dataset and all the query samples (CCLs, PDXs, GEMMs) were found, and only those genes were used as features for building the classifier. Two-thirds of the patient tumor profiles from each cancer category randomly sampled as the training set and the rest were used as a validation set to measure the classifier&#39;s performance (step 1). The training subset were then down-sampled to 500,000 counts per cell (weightedDown_total=5e5), then scaled up such that the total expression per cell was 100000 (transprop_xFact=1e5) and log transformed (step 2). Using log-transformed down-sampled counts, the top 25 differentially over-expressed genes, top 25 differentially under-expressed genes and 25 least differentially expressed genes were found as baseline genes for generating gene-pairs per cancer type (nTopgenes=25) (step 3). A quicker version of pair-transform different from Tan, et al (Tan et al. (2018)) “SingleCellNet: a computational tool to classify single cell RNA-Seq data across platforms and across species,” BioRxiv) (quickPairs=TRUE) was performed by generating gene-pairs among the 75 genes found in step 3 for each cancer type (step 4). The normalized training data were binarized through pair-transformation inspired by the top-pair classifier (Geman et al. (2004) “Classifying gene expression profiles from pairwise mRNA comparisons,” Statistical Applications in Genetics and Molecular Biology 3, p. Article19.). The top 70 most discriminatory gene-pairs for each cancer type were then selected (step 5) (Table 1). Additionally, 70 random gene-pair profiles were generated through random permutations of existing training data (nrand=70) annotated as “rand” or “Unknown” category in which is designed to capture cases where samples in query do not have representation in the cancer categories in the classifier (step 6). Using selected top gene-pairs as features, a CCN random forest classifier of 1000 trees (nTrees=1000) was constructed (step 7). Additionally, stratified sampling in the construction of random forest classifier was used with a strata size of 60 (stratify=TRUE, samplesize=60) to resolve the issue of imbalance profiles quantity across different cancer types. 
     After the CCN classifier was built, 35 held-out samples from each of the cancer categories from the held-out data were randomly sampled and generated 40 “Unknown” profiles for validation (step 8). The held-out data was gene-pair transformed for assessment based on the top gene-pairs selected (step 9). The performance of the classifier was assessed by using precision-recall curve and area under the precision-recall curve (AUPR) (step 10). The process of randomly sampling a training set from all patient tumor data, train classifier and validate using validation set (step 1-10) was repeated 50 times to have a robust assessment of the classifier represented in  FIG. 3B  and  FIG. 4A . After the parameters were tuned based on the performance of classifier on held-out data, a final version CCN classifier was trained using all the TCGA patient tumor data and 2000 trees (nTrees=2000) with all the other parameters staying the same to improve overall robustness and classification power. The specific parameters for the final CCN classifier and can gene-pairs be found in Table 1. The parameters used to train CCN are provided in Table 13. 
     Classifying Query Data into Broad Class 
     The cancer cell lines expression profiles and sample table were downloaded from a portal at the Broad Institute. PDX expression profiles and a sample table were obtained from Gao et al (Gao et al. (2015) “High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response,” Nature Medicine 21(11):1318-1325). GEMM expression profiles were obtained from 10 different studies on GEO database (Adeegbe et al. (2018) “BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response in Kras-Mutant Non-Small Cell Lung Cancer,” Cancer immunology research 6(10):1234-1245; Blaisdell et al. (2015), “Neutrophils oppose uterine epithelial carcinogenesis via debridement of hypoxic tumor cells,” Cancer Cell 28(6):785-799; Fitamant et al. (2015) “YAP inhibition restores hepatocyte differentiation in advanced HCC, leading to tumor regression,” Cell reports 10(10):1692-1707; Jia et al. (2018) “Crebbp loss drives small cell lung cancer and increases sensitivity to HDAC inhibition,” Cancer discovery 8(11):1422-1437; Kress et al. (2016) “Identification of MYC-Dependent Transcriptional Programs in Oncogene-Addicted Liver Tumors,” Cancer Research 76(12):3463-3472; Li et al. (2018) “GKAP acts as a genetic modulator of NMDAR signaling to govern invasive tumor growth,” Cancer Cell 33(4):736-751.e5; Mollaoglu et al. (2018) “The Lineage-Defining Transcription Factors SOX2 and NKX2-1 Determine Lung Cancer Cell Fate and Shape the Tumor Immune Microenvironment,” Immunity 49(4):764-779.e9; Pan et al. (2017) “Whole tumor RNA-sequencing and deconvolution reveal a clinically-prognostic PTEN/PI3K-regulated glioma transcriptional signature,” Oncotarget 8(32):52474-52487; Lissanu Deribe et al. (2018) “Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer,” Nature Medicine 24(7):1047-1057). To use CCN classifier on GEMM data, the mouse genes were converted from GEMM expression profiles into human orthologs. Once a final classifier was trained with all the patient tumor samples, the query samples were gene-pair transformed with gene-pairs selected from the training step and the query samples were classified using CCN. The results were analyzed using R and the classification results were visualized through heatmaps and attribution plots processed using R package ggplot2 (Wickham (2016)  ggplot 2 —Elegant Graphics for Data Analysis . New York, N.Y.: Springer-Verlag New York). 
     Cross-Species Assessment 
     Among the innovative aspects of the CCN tool is the ability for cross species analysis. To assess the performance of cross-species classification, 1003 labelled human tissue/cell type and 1993 labelled mouse tissue/cell type RNA-seq expression profiles were downloaded from Github. The mouse genes were converted into human orthologous genes. Then the intersecting genes were found between mouse tissue/cell expression profiles and human tissue/cell expression profiles. Using the intersecting genes, a CCN classifier was trained with all the human tissue/cell expression profiles. The parameters can be found in Table 3. After the classifier was trained, 75 samples were randomly sampled from each tissue category in mouse tissue/cell data and the classifier was applied on those samples to assess performance. The AUPR is depicted in  FIG. 4C . 
     Cross-Technology Assessment 
     To assess the performance of CCN in applications to microarray, 6219 patient tumor microarray profiles were gathered across 12 different cancer types from the GEO database from more than 100 different projects. The interesting genes between the microarray profiles and TCGA patient RNA-seq profiles were located. Using those genes as features, a CCN classifier was created with all the TCGA patient profiles using hyper-parameters listed in Table 4. The parameters used to train CCN are provided in Table 13. After the microarray specific classifier was trained, 60 microarray patient samples were randomly sampled from each cancer category, and the CCN classifier was applied on them as an assessment of the cross-technology performance. The same CCN classifier was used to classify microarray CCL samples. 
     Training Sub-Type CancerCellNet 
     Eleven cancer types (BRCA, COAD, ESCA, HNSC, KIRC, LGG, PAAD, UCEC, STAD, LUAD, LUSC) were found which have meaningful subtypes based on either histology or expression and sufficient samples in every subtype to train a sub-type classifier with high AUPR. Normal tissue samples were also included from BRCA, COAD, HNSC, KIRC, UCEC to create a normal tissue category in the construction of their sub-type classifier. To train a sub-type classifier, a sample table was manually curated annotating each as either a cancer sub-type or “Unknown” representing other cancer types. Similar to training for broad class classifier, ⅔ of all samples in each sub-type (and “Unknown” category) were randomly sampled as training data. Expression down sampling, gene selections, gene-pair transform and selection (step 2-5 from broad training) were performed using just the samples labelled as a cancer sub-type (excluding samples labelled as “Unknown”) to find discriminating gene pairs that can differentiate sub-type in the broad cancer. Different from the broad class CCN training, the quick version of pair-transform was not used for creating gene-pairs for feature selection. In addition to having gene-pairs as features, the final broad class classifier was applied to all the training samples and the classification scores were added as features to mainly discriminate between the broad cancer type of interest and other cancer types. For some sub-type classifiers, the weight of the broad classification scores were increased as features to fine tune the sub-type classifiers. Some random permutation samples were also generated to add to the “Unknown” training data along with expression profiles of other cancer types. The specific parameters used to train individual sub-type classifiers can be found in Table 5. The parameters used to train CCN are provided in Table 13. 
     An equal amount across all sub-types and Unknown category in the held-out data was then sampled for assessing the sub-type classifiers through AUPR. The process was repeated 20 times for robust assessment of the sub-type classifiers. The results are shown in  FIG. 4E . For the final sub-type classifiers of the 11 broad categories, all of the TCGA data was used. 
     Classifying Query Data into Sub-Type 
     The 11 sub-type classifiers were applied on query samples when available. Heatmap visualizations were done using ComplexHeatmap package (Gu et al. (2016) “Complex heatmaps reveal patterns and correlations in multidimensional genomic data,” Bioinformatics 32(18):2847-2849) and other analysis were done in R. 
     Results 
     CancerCellNet Classifies Samples Accurately Across Species and Technologies 
     A computational tool was previously developed using the Random Forest classification method to measure the similarity of engineered cell populations with their in vivo counterparts based on transcriptional profiles (Cahan et al. (2014) “CellNet: network biology applied to stem cell engineering,”. Cell, 158(4):903-915.; Radley et al. (2017) “Assessment of engineered cells using CellNet and RNA-seq,” Nature Protocols 12(5):1089-1102). This approach was recently elaborated to allow for classification of single cell RNA-Seq data in a manner that allows for cross-platform and cross-species analysis (Tan et al. (2018) “SingleCellNet: a computational tool to classify single cell RNA-Seq data across platforms and across species,” BioRxiv.). In the present example, an approach was used to quantitatively compare cancer models to naturally occurring patient tumors ( FIG. 3A ). In brief, The Cancer Genome Atlas (TCGA) expression data was used from 25 solid tumor types to train a top-pair multi-class Random forest classifier. The approach also included an ‘Unknown’ category trained on a random shuffling and sampling of profiles from the remaining 24 tumor types in the training data to identify query samples that are not reflective of any of the training data. 
     The performance of this approach was assessed by computing the area under the precision recall curves derived by k-fold cross validation (n=50) ( FIG. 3B  and  FIG. 4A ). In the k-fold cross validation, the mean AUPR exceeded 0.95 in most of the tumor types and was below 0.7 only for the READ and COAD categories. This is not surprising as READ and COAD are considered to be the same disease. In addition to achieving high mean AUPRs on held-out TCGA data, it was found that CCN also achieved high AUPR (above 0.9) when it was applied to independent testing data from ICGC consisting RNA-Seq data from 886 tumors across 5 tumor types ( FIG. 4B ) (Zhang et al. (2011) “International Cancer Genome Consortium Data Portal—a one-stop shop for cancer genomics data,”  Database: the Journal of Biological Databases and Curation , p. bar026). 
     One of the aims of the study was to compare distinct cancer models, including GEMMs, the exemplary method was able to classify samples from mouse and human samples equivalently. The Top-Pair transform, previously described (Tan et al. (2018) “SingleCellNet: a computational tool to classify single cell RNA-Seq data across platforms and across species,” BioRxiv), was used to achieve this and the feasibility of this approach was tested by assessing the performance of a normal (i.e., non-tumor) human tissue classifier as applied to mouse tissues. Consistent with prior applications, it was found that the cross-species classifier performed well, achieving mean AUPR of 0.93 when applied to mouse data ( FIG. 4C ). 
     To evaluate cancer models at a finer resolution, an approach was developed to perform tumor sub-type classifications ( FIG. 4D ). Eleven different cancer sub-type classifiers were constructed based on the availability of expression or histological subtype information (Cancer Genome Atlas Network (2012), “Comprehensive molecular portraits of human breast tumours,” Nature 490(7418):61-70; Parker et al. (2009), “Supervised risk predictor of breast cancer based on intrinsic subtypes,”  Journal of Clinical Oncology  27(8): 1160-1167; Cancer Genome Atlas Network (2012), “Comprehensive molecular characterization of human colon and rectal cancer,” Nature 487(7407):330-337; Cancer Genome Atlas Research Network (2017), “Integrated genomic characterization of pancreatic ductal adenocarcinoma,”  Cancer Cell  32(2):185-203.e13; Cancer Genome Atlas Network (2015), “Comprehensive genomic characterization of head and neck squamous cell carcinomas,”  Nature  517(7536):576-582; Cancer Genome Atlas Research Network (2013), “Comprehensive molecular characterization of clear cell renal cell carcinoma,” Nature 499(7456):43-49; Verhaak et al. (2010), “Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1,” Cancer Cell 17(1):98-110; Cancer Genome Atlas Research Network (2014), “Comprehensive molecular profiling of lung adenocarcinoma,” Nature 511(7511): 543-550; Wilkerson et al. (2010), “Lung squamous cell carcinoma mRNA expression subtypes are reproducible, clinically important, and correspond to normal cell types,” Clinical Cancer Research 16(19):4864-4875; Cancer Genome Atlas Research Network, Analysis Working Group: Asan University, BC Cancer Agency, et al. (2017), “Integrated genomic characterization of oesophageal carcinoma,” Nature 541(7636):169-175; Hu et al. 2012; Cancer Genome Atlas Research Network, Kandoth et al. (2013) “Integrated genomic characterization of endometrial carcinoma,” Nature 497(7447):67-73). Non-cancerous, normal tissues were also included when available for several sub-type classifiers (BRCA, COAD, HNSC, KIRC and UCEC). The 11 sub-type classifiers all achieved high overall AUPRs ranging from 0.78 to 0.98 ( FIG. 4E ). 
     Fidelity of Cancer Cell Lines 
     Having validated the performance of CCN, it was then used to determine the fidelity of CCLs. RNA-seq expression data of 657 different cell lines was mined across 20 cancer types from Cancer Cell Line Encyclopedia (CCLE) and CCN was applied to them, finding a wide classification range for cell lines of each tumor type ( FIG. 5A ). To verify the classification results, CCN was applied to CCLE expression profiles generated through microarray expression profiling. To ensure that CCN would function on microarray data, CNN was applied to 720 expression profiles of 12 tumor types from GEO. The cross-platform CCN classifier performed well, based on comparison to study-provided annotation, achieving a mean AUPRs of 0.94 ( FIG. 6A ). Next, this was applied cross-platform classifiers to microarray expression profiles of CCLE ( FIG. 6B ). From the classification results of 571 cell lines that have both RNA-seq and microarray expression profiles, a strong positive association was found between the classification scores from RNA-seq and those from microarray ( FIG. 6C ). This comparison supports the notion that the classification scores for each cell line are not artifacts of profiling methodology. Moreover, this comparison shows that the scores are consistent between the times that the cell lines were first assayed by microarray expression profiling in 2012 and by RNA-Seq in 2019, further validating the robustness of the CCN results. 
     Next, the CCN scores of CCLE cell lines was categorized based on the proportion of lines associated with each tumor type that were correctly classified. A decision threshold of 0.266 was set, which was selected as it represents the 5th percentile of all TCGA held-out classification scores to ensure at least 95% true positive rate for the held-out data. Each cell line was placed into one of five categories based on its CCN profile: correctly classified, mix-correctly classified, not classified, mix incorrectly classified and incorrectly classified ( FIG. 5B ). Cell lines originally annotated as BRCA, CESC SKCM and SARC had a high proportion of lines correctly classified. The COAD_READ cell lines had a high proportion of cell lines with mixed classification, reflecting the similarities of the tumor samples in the COAD and READ training data. Seventeen out of twenty tumor types had greater than 25% of lines that received no classification. In particular, no ESCA, GBM and LGG cell lines were classified as such, suggesting that these tumor types need more faithful cell line models ( FIGS. 5  A and B). 
     One way to explain low classification scores is that some cell lines are derived from and represent sub-types of tumors that are not well-represented in TCGA. To explore this hypothesis, tumor sub-type classification was first performed on the CCLE lines from 11 tumor types for which sub-type classifiers had been trained. It was reasoned that if a cell was a good model for a rarer sub-type, then it would receive a poor general classification but a high classification for the sub-type that it models well. Therefore, the number of lines that fit this pattern was counted. It was found that of the 198 lines with no general classification, 52 (26%) were classified as a specific sub-type, suggesting that derivation from rare sub types is not the major contributor to poor overall CCL classification. 
     Another potential contributor to low scoring cell lines could be the intra-tumor impurity in the training data. If impurity were such a confounder of CCN scoring, then a positive correlation between mean purity and mean CCN classification of CCLE per general tumor type would be expected. However low Pearson correlation of 0.076 between the mean purity and mean CCN classification scores of CCLE was found, suggesting that tumor purity is not a major contributor to the low scoring of CCLEs ( FIG. 5D ). 
     Next, the sub-type classification of CCLs from three general tumor types was explored in more depth, focusing first on Uterine Corpus Endometrial Carcinoma (UCEC). The histological based sub-types of UCEC, endometrioid and serous histological type, differ in prevalence, molecular properties, prognosis, and treatment (Black et al. (2014), “Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer,”  Women&#39;s health  ( London, England ) 10(1):45-57; Yang et al. (2011), “Progesterone: the ultimate endometrial tumor suppresso,” Trends in Endocrinology and Metabolism 22(4):145-152). CCN classified the majority of the UCEC cell lines as serous. All of the other lines were classified as ‘unknown’ except for JHUEM-1 and HEC-265, which received a mixed serous and endometrioid, meaning that the classification of each sub-type exceeded the 5th percentile of TCGA held-out classification scores ( FIG. 5C ). The preponderance of serous versus endometroid may be due to properties of serous cancer cells that aid propagation in vitro, such as upregulation in cell adhesion (Huszar et al. (2010), “Up-regulation of L1CAM is linked to loss of hormone receptors and E-cadherin in aggressive subtypes of endometrial carcinomas,”  The Journal of Pathology  220(5):551-561) helps the derivation of CCLs. Some of the sub-type classification results are consistent with prior observations. For example, HEC-1A, HEC-1B, and KLE were previously characterized as endometrial (Kozak et al. (2018) “A guide for endometrial cancer cell lines functional assays using the measurements of electronic impedance,”  Cytotechnology  70(1):339-350). On the other hand, the sub-type classification results contradict prior observations in at least one case. For example, Ishikawa ER− has been used as a model of endometroid cancer (Korch et al. (2012), “DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination,” Gynecologic Oncology 127(1):241-248; Kozak et al. (2018) “A guide for endometrial cancer cell lines functional assays using the measurements of electronic impedance,”  Cytotechnology  70(1):339-350), CCN classified the Ishikawa 02 ER− cell line strongly as serous. This could be a result of ER negative being a characteristic of type 2 endometrial cancer (Black et al. (2014), “Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer,” Women&#39;s health (London, England) 10(1): 45-57). Taken together, these results indicate a need for more endometroid-like CCLs. 
     Next, the sub-type classification of Lung Squamous Cell Carcinoma (LUSC) cell lines ( FIG. 5D ) was examined. It was found that of the 19 lines unclassified or misclassified in the general classifier, 16 (84%) were considered to be the unknown sub-type. These three lines had general classification scores modestly below the threshold; two had sub-type classification as primitive, and one as a mix of basal, primitive and secretory. Among all of the cell LUAD lines that were classified, all the cell lines have underlying primitive subtype classification. This is consistent either with the ease of deriving lines from tumors with a primitive character, or with a process by which cell line derivation promotes similarity to more the primitive sub-type, which is marked by increased cellular proliferation (Wilkerson et al. (2010), “Lung squamous cell carcinoma mRNA expression subtypes are reproducible, clinically important, and correspond to normal cell types,” Clinical Cancer Research 16(19):4864-4875). The results are consistent with prior reports that have investigated the resemblance of some lines to LUAD sub-types. For example, HCC-95, classified as classical and primitive subtype, has previously been characterized as classical (Wu et al. (2013), “Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity,” British Journal of Cancer 109(6):1599-1608; Wilkerson et al. (2010), “Lung squamous cell carcinoma mRNA expression subtypes are reproducible, clinically important, and correspond to normal cell types,” Clinical Cancer Research 16(19):4864-4875). Further, LUDLU-1, classified as a mix of primitive, basal and classical, was previously characterized as resembling both basal and classical (Wu et al. (2013), “Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity,” British Journal of Cancer 109(6):1599-1608). Lung Adenocarcinoma (LUAD) cell lines had classification results similar to LUSC: most lines did not classify as LUAD in the general classifier (53 of 76), and most of the remaining lines exhibited mixed sub-type classification ( FIG. 5E ). RERF-LC-Ad1 had the highest general classification score and the highest proximal inflammation sub-type classification score. Taken together, these sub-type classification results have revealed an absence of cell lines models for basal, classical, and secretory LUSC, and for the TRU LUAD sub-type. 
     Finally, it was sought to measure the extent to which cell line transcriptional fidelity related to model use. The number of papers in which a model was mentioned was used, normalized by the number of years since the cell line was derived, as a rough approximation of model usage. To explore this metric, the normalized citation count was plotted versus general classification score, labeling the highest cited and highest classified cell lines from each general tumor type ( FIG. 5F ). For most of the general tumor types, the highest cited cell line is not the highest classified cell line except for Hep G2 and ML-1, representing LIHC and THCA, respectively. On the other hand, the general scores of the highest cited cell lines representing BRCA, LUAD, OV, PRAD and SKCM fall below the classification threshold of 0.266. Notably, each of these tumor types have lines with scores exceeding 0.5, suggesting that these lines should be considered as more faithful transcriptional models when selecting lines for a study. 
     Evaluation of Patient Derived Xenografts 
     Next, it was sought to evaluate a more recent class of cancer models: PDX. To do so, the RNA-Seq expression profiles of 415 PDX models from 13 different types of cancer types generated previously (Gao et al. (2015), “High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response,” Nature Medicine 21(11):1318-1325) were subjected to CCN. Similar to the results of CCLE, the PDXs exhibited a wide range of classification scores ( FIG. 7A ). By categorizing the CCN scores of PDX based on the proportion of samples associated with each tumor type that were correctly classified, it was found that SARC, SKCM and BRCA have higher proportion of correctly classified PDX than those of other cancer categories ( FIG. 7B ). In contrast to CCLE, it was found a higher proportion of correctly classified PDX in STAD and KIRC ( FIG. 7B ). However, similar to CCLE, no ESCA PDXs correctly classified. This held true when sub-type classification was performed on PDX samples: none of the PDX in ESCA were classified as any rare ESCA subtypes ( FIG. 11 ). UCEC PDXs had both endometrioid subtypes, serous subtypes, and mixed subtypes, which provides broader representation than in CCLE ( FIG. 8C ). LUSC PDXs had a large proportion HNSC misclassified, yet strong as basal and classical subtype classification ( FIG. 8D ). This could be due to result from the similarity in expression profiles of basal and classical subtypes of HNSC and LUSC (Walter et al. (2013), “Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes,” Plos One 8(2):e56823; Wickham (2016)  ggplot 2 —Elegant Graphics for Data Analysis , New York, N.Y.: Springer-Verlag New York). No LUSC PDXs lack were classified as the secretory subtype ( FIG. 8D ). While 9 of the LUAD PDX samples were classified as the unknown sub-type class classification, the remaining 5 classify as proximal proliferative or mixed proximal proliferative and proximal inflammatory ( FIG. 9 ). Finally, similar to the CCLE, there were no TRU subtypes in the PDX cohort ( FIG. 9 ). Collectively, these results indicate that PDXs can have very high transcriptional fidelity to both general tumor types and sub-types. 
     Evaluation of GEMMs 
     Next, CCN was used to evaluate GEMMs of six general tumor types from ten studies for which expression data was publicly available (Adeegbe et al. (2018) “BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response in Kras-Mutant Non-Small Cell Lung Cancer,” Cancer immunology research 6(10):1234-1245; Blaisdell et al. (2015), “Neutrophils oppose uterine epithelial carcinogenesis via debridement of hypoxic tumor cells,” Cancer Cell 28(6):785-799; Fitamant et al. (2015) “YAP inhibition restores hepatocyte differentiation in advanced HCC, leading to tumor regression,” Cell reports 10(10):1692-1707; Jia et al. (2018) “Crebbp loss drives small cell lung cancer and increases sensitivity to HDAC inhibition,” Cancer discovery 8(11):1422-1437; Kress et al. (2016) “Identification of MYC-Dependent Transcriptional Programs in Oncogene-Addicted Liver Tumors,” Cancer Research 76(12):3463-3472; Li et al. (2018) “GKAP acts as a genetic modulator of NMDAR signaling to govern invasive tumor growth,” Cancer Cell 33(4):736-751.e5; Mollaoglu et al. (2018) “The Lineage-Defining Transcription Factors SOX2 and NKX2-1 Determine Lung Cancer Cell Fate and Shape the Tumor Immune Microenvironment,” Immunity 49(4):764-779.e9; Pan et al. (2017) “Whole tumor RNA-sequencing and deconvolution reveal a clinically-prognostic PTEN/PI3K-regulated glioma transcriptional signature,” Oncotarget 8(32):52474-52487; Lissanu Deribe et al. (2018) “Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer,” Nature Medicine 24(7):1047-1057). As was true for CCLs and PDXs, GEMMs also had a wide range of CCN scores ( FIG. 8A ). The CCN scores were next categorized based on the proportion of samples associated with each tumor type that were correctly classified ( FIG. 8B ). In contrast to CCLs and PDXs, the GEMM dataset included multiple replicates per model, which allowed for the examination of intra-GEMM variability. Both at the level of CCN score and at the level of categorization, GEMMs were highly invariant. For example, replicates of LUAD GEMMs (driven by Kras mutation and loss of p53 (Adeegbe et al. (2018) “BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response in Kras-Mutant Non-Small Cell Lung Cancer,” Cancer immunology research 6(10):1234-1245), and Smarca4 loss (Lissanu Deribe et al. (2018) “Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer,” Nature Medicine 24(7):1047-1057), or overexpression of Sox2 and loss of Lkb1 (Mollaoglu et al. (2018) “The Lineage-Defining Transcription Factors SOX2 and NKX2-1 Determine Lung Cancer Cell Fate and Shape the Tumor Immune Microenvironment,” Immunity 49(4):764-779.e9) were all correctly classified ( FIG. 8B ). GEMMs sharing genotypes across studies, such as Pgr(cre/+)Pten(lox/lox)-driven UCEC (Blaisdell et al. (2015), “Neutrophils oppose uterine epithelial carcinogenesis via debridement of hypoxic tumor cells,” Cancer Cell 28(6):785-799; Daikoku et al. (2008) “Conditional loss of uterine Pten unfailingly and rapidly induces endometrial cancer in mice,” Cancer Research 68(14):5619-5627) received highly similar general and sub-type classification scores ( FIG. 9 ). Even GEMMs with mixed classifications received consistent CCN scores. For example, LGG GEMMs, generated by Nf1 mutations expressed in different neural progenitors in combination with Pten deletion (Pan et al. (2017) “Whole tumor RNA-sequencing and deconvolution reveal a clinically-prognostic PTEN/PI3K-regulated glioma transcriptional signature,” Oncotarget 8(32):52474-52487), consistently received mixed classification as both LGG and GBM ( FIG. 8A ). 
     To explore the extent to which driver genotype impacts sub-type classification, two general tumor types were examined in which there were GEMMs with different tumor drivers: LUSC and LUAD. The LUSC GEMMs were generated using loss of Lkb1 and either overexpression of Sox2 (via two distinct mechanisms) or loss of Pten (Mollaoglu et al. (2018) “The Lineage-Defining Transcription Factors SOX2 and NKX2-1 Determine Lung Cancer Cell Fate and Shape the Tumor Immune Microenvironment,” Immunity 49(4):764-779.e9). It was found that most of the lenti-Sox2-Cre-infected;Lkb1 fl/fl  samples were classified as LUSC, whereas the majority of the Rosa26LSL-Sox2-1RES-GFP;Lkb1 fl/fl  samples were classified as either LUAD or a mixture of LUAD and LUSC ( FIG. 8C ). It is possible that the distinct transcriptional programs result from differing levels of exogenous Sox2 expression in these models, and that the samples with mixed classification results reflect an adenosquamous carcinoma phenotype. Most of the Lkb1 fl/fl ;Pten fl/fl  GEMMs were classified as ‘unknown’. Moreover, the sub-type classification indicated that this GEMM was either unknown or of mixed serous/primitive sub-type, in contrast to prior reports suggesting that it is most similar to a basal subtype (Xu et al. (2014) “Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression,” Cancer Cell 25(5):590-604). The results have shown that Lkb1fl/fl,Ptenfl/fl GEMMs are mostly classified as unknown and primitive, secretory subtypes which correlates with the general classification scores. The lenti-Sox2-Cre-infected;Lkb1 fl/fl  samples were more strongly classified as the secretory sub-type, whereas the Rosa26LSL-Sox2-1RES-GFP;Lkb1 fl/fl  samples were classified as a more balanced mix of serous and primitive sub-types. None of the three LUSC GEMMs were sub-typed as classical or basal. All of the LUAD GEMMs, which were generated using various combinations of activating Kras mutation, loss of Trp53, loss of Lkb1, and loss of Smarca4L (Lissanu Deribe et al. (2018) “Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer,” Nature Medicine 24(7):1047-1057; Adeegbe et al. (2018) “BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response in Kras-Mutant Non-Small Cell Lung Cancer,” Cancer immunology research 6(10):1234-1245); Mollaoglu et al. (2018) “The Lineage-Defining Transcription Factors SOX2 and NKX2-1 Determine Lung Cancer Cell Fate and Shape the Tumor Immune Microenvironment,” Immunity 49(4):764-779.e9), were correctly classified ( FIG. 8D ). There were no substantial differences in general, or sub-type classification across driver genotypes. Notably, the sub-types tended to be a mixture of proximal proliferation, proximal inflammation and TRU. Taken together, this analysis suggests that there is a degree of similarity, and perhaps plasticity between the primitive and secretory (but not basal or classical) sub-types of LUSC. On the other hand, while the LUAD GEMMs classify strongly as LUAD, all have a mixed sub-type classification—a result that does not vary by genotype. 
     Comparison of CCLs, PDXs, and GEMMs 
     Finally, it was sought to estimate the comparative transcriptional fidelity of the three cancer models modalities, limiting the comparison to those five general tumor types for which there were at least two examples per modality: UCEC, PAAD, LUSC, LUAD, and LIHC. The general CCN scores of each model were compared on a per tumor type basis ( FIG. 10 ). In the case of GEMMs, the mean classification score of all samples with shared genotypes was used. It was found that GEMMs had the highest median general classification scores in four out of the five tumor types. However, some PDXs achieved the highest classification scores. In UCEC, LUAD and LIHC, the maximum classification score of PDXs exceeded 0.75 and were thus comparable to the majority of scores on held out TCGA data, highlighting the potential for PDXs to mirror the transcriptional state of natural tumors ( FIG. 10 ). 
     It was also sought to compare model modalities in terms of the diversity of sub-types that they represent. As a reference, the overall sub-type incidence was also included in this analysis, as approximated by incidence in TCGA. In models of UCEC, there is a notable difference in endometroid incidence, and the proportion of models classified as endometroid, with only PDX having any representatives ( FIG. 10 ). The vast majority of CCLE and all of the GEMM models of PAAD have an unknown sub-type classification. However, the PDXs are sub-typed as either a mixture of basal and classical, or classical alone. No model of LUSC was sub-typed exclusively as secretory, and only PDXs were sub-typed exclusively as basal. No model of LUAD was sub-typed exclusively as TRU, but there were models that were sub-typed exclusively as proximal proliferative in both PDXs and GEMMs. Taken together, these results indicate that only a few CCLs are good transcriptional exemplars of natural tumor sub-types, that GEMMs are typically mixtures of sub-types, and the PDXs are the modality that can best reflect specific sub-types. 
     Discussion 
     A major goal in the field of cancer biology is to develop models that mimic naturally occurring tumors with enough fidelity to enable therapeutic discoveries. However, methods to measure the extent to which cancer models resemble or diverge from native tumors are lacking. This is especially problematic now because there are many existing models from which to choose, and it has become easier to generate new models. Accordingly, in certain aspects, this disclosure presents CancerCellNet (CCN), a computational tool that measures the similarity of cancer models to 25 naturally occurring tumor types and 46 sub-types. Because CCN is platform and species agnostic, it can be applied across many model modalities, including CCLs, PDXs, and GEMMs, and thus it represents a consistent platform to compare models across modalities. In this example, CCN was applied to 657 cancer cell lines, 415 patient derived xenografts, and 26 distinct genetically engineered mouse models. Several exemplary lessons emerged from these computational analyses that have implications for the field of cancer biology. 
     First, CancerCellNet indicates that GEMMs are transcriptionally the most faithful models of four out of five general tumor types for which data from all modalities was available. This is consistent with the fact that GEMMs are typically derived by recapitulating well defined driver mutations of natural tumors, and thus this observation corroborates the importance of genetics in the etiology of cancer. Moreover, in contrast to PDXs, GEMMs are typically generated in immune replete (complete) hosts. Therefore, the higher fidelity of GEMMs may also be a result of the influence of a native immune system on GEMM tumors. Second, PDXs and CCLs have lower scores that are comparable to each other. This is consistent with the observation that PDXs can undergo selective pressures in the host that distort the progression of genomic alterations away from what is observed in natural tumors (Ben-David et al. (2017) “Patient-derived xenografts undergo mouse-specific tumor evolution,” Nature Genetics 49(11):1567-1575). Furthermore, the observation that a few PDXs have very high classification scores, approaching a level that is indistinguishable from held out TCGA data, suggests that under certain conditions, PDX can almost perfectly mimic natural tumors transcriptionally. It is unclear what these conditions are; it may be that these few PDXs were profiled prior to the acquisition of non-typical genomic alterations. Third, it was found that none of the samples that we evaluated here are transcriptionally adequate models of ESCA, and therefore this tumor type requires further attention to derive new models. Fourth, it was found that in several tumor types, GEMMs tend to reflect mixtures of sub-types rather than conforming to single sub-types. The reasons for this are not clear but it is possible that in the cases that were examined, the histologically defined sub-types have a degree of plasticity that is exacerbated in the murine host environment. 
     CCN includes various embodiments or aspects. For example, CCN is based on transcriptomic data in some embodiments, but other molecular readouts of tumor state are also optionally utilized in lieu of, or in combination with, transcriptomic data, such as profiles of the proteome, epigenome, non-coding RNA-ome, and genome, among others, can also be mimicked in a model system. It is possible that some models reflect tumor behavior well, and because this behavior is not well predicted by transcriptome alone, these models have lower CCN scores. To both measure the extent that such situations exist, and to correct for them, other omic data is optionally incorporated into CCN so as to make more accurate and integrated model evaluation possible. Further, in the cross-species analysis, CCN generally implicitly assumes that homologs are functionally equivalent. The extent to which they are not functionally equivalent determines how confounded the CCN results will be. However, this possibility may be of limited consequence based on the high performance of the normal tissue cross-species classifier, and based on the fact that GEMMs have the highest median CCN scores. In addition, the TCGA training data is made up of RNA-Seq from bulk tumor samples, which necessarily includes non-tumor cells, whereas the CCLs are by definition cell lines of tumor origin. Therefore, CCLs theoretically could have artificially low CCN scores due to the presence of non-tumor cells in the training data. This potential problem appears to be limited as no correlation between tumor purity and CCN score was found in the CCLE samples. However, this potential problem may be related to the question of intra-tumor heterogeneity. Thus, in certain embodiments, CCN can be extended to interpret single cell RNA-Seq data. A sufficient amount of training single cell RNA-Seq data enables CCN to not only evaluate models on a per cell type basis, but also based on cellular composition. 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Gene Pairs For General Tumor Types 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 BRCA 
                 GBM 
                 OV 
                 LUAD 
                 UCEC 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 BRCA_1 
                 BRCA_2 
                 GBM_1 
                 GBM_2 
                 OV_1 
                 OV_2 
                 LUAD_1 
                 LUAD_2 
                 UCEC_1 
                 UCEC_2 
               
               
                   
               
               
                 LMX1B 
                 MIB2 
                 PSRC1 
                 FLNB 
                 WT1 
                 TAF15 
                 NAPSA 
                 PPP2R1A 
                 DLX5 
                 PRNP 
               
               
                 LMX1B 
                 ANKS6 
                 KLHDC8A 
                 FLNB 
                 WT1 
                 SUN2 
                 SFTA2 
                 ITPK1 
                 DLX6 
                 NR3C1 
               
               
                 LMX1B 
                 ID1 
                 C21orf62 
                 NET1 
                 WT1 
                 DST 
                 SFTA2 
                 OAF 
                 DLX5 
                 SBDS 
               
               
                 TRPS1 
                 ODC1 
                 NR2E1 
                 NET1 
                 KCNK15 
                 ORMDL3 
                 SFTA2 
                 PLCD3 
                 DLX5 
                 RNF13 
               
               
                 PRLR 
                 ETS2 
                 LCTL 
                 FAM83H 
                 KLHL14 
                 ORMDL3 
                 NAPSA 
                 PTMS 
                 MSX1 
                 SBDS 
               
               
                 AARD 
                 ANKS6 
                 GAP43 
                 NUCKS1 
                 ZNF503 
                 TAF15 
                 NAPSA 
                 HNRNPC 
                 DLX6 
                 TBC1D2B 
               
               
                 TRPS1 
                 HADHA 
                 PSRC1 
                 TRIM27 
                 KCNK15 
                 RETSAT 
                 ROS1 
                 SLC16A1 
                 DLX6 
                 LYPLAL1 
               
               
                 TRPS1 
                 EIF3L 
                 CNR1 
                 NET1 
                 KLHL14 
                 USP47 
                 SFTPD 
                 CELSR2 
                 MSX1 
                 CALCOCO2 
               
               
                 PRLR 
                 ODC1 
                 PSRC1 
                 HTATSF1 
                 KCNK15 
                 DNAJC3 
                 ROS1 
                 CELSR2 
                 MSX1 
                 TACC1 
               
               
                 IRX5 
                 ESRRA 
                 RNASE2 
                 FAM83H 
                 KLHL14 
                 DNAJC7 
                 SCGB3A2 
                 SLC16A1 
                 MAP2K6 
                 TAOK3 
               
               
                 AARD 
                 PSAT1 
                 C21orf62 
                 DSTYK 
                 ZNF503 
                 NAP1L4 
                 SFTPA1 
                 CELSR2 
                 STX18 
                 CALCOCO2 
               
               
                 EFHD1 
                 ITM2C 
                 RFX4 
                 HTATSF1 
                 DOK5 
                 DST 
                 ROS1 
                 PHGDH 
                 STX18 
                 SERINC3 
               
               
                 IRX5 
                 MIB2 
                 RNASE2 
                 DSP 
                 ATP6V1B1 
                 ORMDL3 
                 SFTPA1 
                 PHGDH 
                 SOX17 
                 CREBL2 
               
               
                 IRX5 
                 ID1 
                 NR2E1 
                 NT5DC1 
                 DOK5 
                 SPAG9 
                 SFTPC 
                 HR 
                 STX18 
                 TM9SF4 
               
               
                 AARD 
                 FZD5 
                 PLA2G5 
                 MYO1D 
                 ATP6V1B1 
                 NAP1L4 
                 BPIFA1 
                 HR 
                 SOX17 
                 PRNP 
               
               
                 PRLR 
                 ETFB 
                 NR2E1 
                 LSR 
                 ZNF503 
                 NBR1 
                 SFTPA1 
                 SOX9 
                 CCDC157 
                 LYPLAL1 
               
               
                 GATA3 
                 GSTP1 
                 LCTL 
                 BAIAP2L1 
                 DOK5 
                 ABR 
                 SFTPD 
                 ECSIT 
                 TEKT2 
                 LYPLAL1 
               
               
                 GATA3 
                 ITM2C 
                 C21orf62 
                 MYO1D 
                 ATP6V1B1 
                 TAF15 
                 SFTPD 
                 TIMM44 
                 SOX17 
                 TBC1D2B 
               
               
                 TBC1D9 
                 HADHA 
                 LCTL 
                 DSP 
                 PNOC 
                 PPP3CC 
                 COL6A5 
                 HR 
                 MAP2K6 
                 SBDS 
               
               
                 PIP 
                 PSAT1 
                 PLA2G5 
                 LSR 
                 NPR1 
                 NBR1 
                 SCGB3A2 
                 PHGDH 
                 FGF18 
                 PLSCR4 
               
               
                 GATA3 
                 ETS2 
                 PLA2G5 
                 KIAA1217 
                 LYPD1 
                 DST 
                 SFTPC 
                 SLC16A1 
                 FGF18 
                 NR3C1 
               
               
                 EFHD1 
                 CKB 
                 HEPACAM 
                 HTATSF1 
                 LYPD1 
                 NAP1L4 
                 SFTPC 
                 SYNGR1 
                 MAP2K6 
                 RNF13 
               
               
                 PLEKHF2 
                 ODC1 
                 RNASE2 
                 LSR 
                 NPR1 
                 SUN2 
                 SCGB3A2 
                 LARP6 
                 ARMC3 
                 PLSCR4 
               
               
                 CILP 
                 ITM2C 
                 POU3F2 
                 BRD3 
                 PNOC 
                 ELL2 
                 LGSN 
                 PLEKHH1 
                 ARMC3 
                 NR3C1 
               
               
                 SLC16A6 
                 ANKS6 
                 GAP43 
                 CNDP2 
                 PNOC 
                 NIPA1 
                 TREM1 
                 OAF 
                 FGF18 
                 NEDD4 
               
               
                 NAT1 
                 UBE2E3 
                 KLHDC8A 
                 JUP 
                 NPR1 
                 SPAG9 
                 TREM1 
                 PLCD3 
                 HOXB6 
                 CALCOCO2 
               
               
                 ESR1 
                 GSTP1 
                 CNR1 
                 FLNB 
                 LYPD1 
                 SPAG9 
                 LGSN 
                 PPT2 
                 TEKT2 
                 PLSCR4 
               
               
                 FSIP1 
                 STARD4 
                 RNASE3 
                 HOOK1 
                 DOK7 
                 LRP11 
                 CCNJL 
                 ECSIT 
                 EMX2 
                 PRNP 
               
               
                 PIP 
                 FZD5 
                 MT3 
                 NUCKS1 
                 DOK7 
                 TMEM181 
                 CCNJL 
                 TIMM44 
                 RNF183 
                 ADCY9 
               
               
                 PIP 
                 MID1 
                 POU3F2 
                 DSTYK 
                 RSPO1 
                 LRP11 
                 SFTPB 
                 PPP2R1A 
                 ELP3 
                 SERINC3 
               
               
                 SERTAD4 
                 RNF145 
                 KLHDC8A 
                 MYO1C 
                 RSPO1 
                 PPP3CC 
                 LPCAT1 
                 PPP2R1A 
                 RNF183 
                 TAOK3 
               
               
                 NAT1 
                 RNF145 
                 RNASE3 
                 ARHGEF5 
                 RSPO1 
                 STK39 
                 SFTPB 
                 PTMS 
                 EMX2 
                 MAF 
               
               
                 NAT1 
                 PPARA 
                 CNR1 
                 DSTYK 
                 DOK7 
                 TOM1 
                 TBX4 
                 SYNGR1 
                 EMX2 
                 CREBL2 
               
               
                 FSIP1 
                 PRKCA 
                 DBX2 
                 DSP 
                 MEIS1 
                 NBR1 
                 SFTPB 
                 HNRNPC 
                 C2orf88 
                 TACC1 
               
               
                 FSIP1 
                 PSAT1 
                 RFX4 
                 BRD3 
                 CTU1 
                 STK39 
                 NKX2-1 
                 WIZ 
                 RNF183 
                 ELL2 
               
               
                 CILP 
                 RNF145 
                 RNASE3 
                 BAIAP2L1 
                 MEIS1 
                 SUN2 
                 LGSN 
                 OAF 
                 DACT2 
                 FKBP5 
               
               
                 SLC16A6 
                 PPARA 
                 DBX2 
                 HOOK1 
                 SOX17 
                 ABR 
                 NKX2-1 
                 TIMM44 
                 ASRGL1 
                 SERINC3 
               
               
                 SLC16A6 
                 SLC9A6 
                 S100B 
                 NUCKS1 
                 SOX17 
                 DNAJC7 
                 NKX2-1 
                 ECSIT 
                 C2orf88 
                 TAOK3 
               
               
                 TBC1D9 
                 EIF3L 
                 GAP43 
                 WFS1 
                 CTU1 
                 LRP11 
                 TBX4 
                 LARP6 
                 HOXB6 
                 TACC1 
               
               
                 CILP 
                 ETS2 
                 GFAP 
                 JUP 
                 SOX17 
                 GGNBP2 
                 MUC21 
                 PLCD3 
                 HOXB6 
                 SETD7 
               
               
                 EFHD1 
                 BIN1 
                 DBX2 
                 NT5DC1 
                 HTR3A 
                 STK39 
                 BMP5 
                 PPT2 
                 TEKT2 
                 ADCY9 
               
               
                 ST8SIA6 
                 PRKCA 
                 GFAP 
                 MYO1C 
                 HTR3A 
                 ELL2 
                 LPCAT1 
                 HNRNPC 
                 DACT2 
                 CREBL2 
               
               
                 LRRC15 
                 PFKP 
                 GFAP 
                 STAT6 
                 KLK7 
                 ABR 
                 CCNJL 
                 ERF 
                 ARMC3 
                 NEDD4 
               
               
                 SERTAD4 
                 UBE2E3 
                 PMP2 
                 PERP 
                 HTR3A 
                 NIPA1 
                 BMP5 
                 LDLRAD3 
                 C2orf88 
                 RNF13 
               
               
                 ST8SIA6 
                 FZD5 
                 PMP2 
                 MYO1D 
                 MAMSTR 
                 PPP3CC 
                 BMP5 
                 PLEKHH1 
                 ASRGL1 
                 USP22 
               
               
                 SERTAD4 
                 PITPNM1 
                 POU3F2 
                 GTF3C4 
                 IMPG2 
                 GALK2 
                 BPIFA1 
                 LARP6 
                 DACT2 
                 SETD7 
               
               
                 ST8SIA6 
                 STARD4 
                 PMP2 
                 LTBR 
                 UPK3B 
                 ELL2 
                 XKRX 
                 PLEKHH1 
                 CCDC157 
                 ADCY9 
               
               
                 LRRC15 
                 PITPNM1 
                 MT3 
                 STAT6 
                 MEIS1 
                 DNAJC3 
                 TREM1 
                 ERF 
                 CCDC157 
                 NEDD4 
               
               
                 LRRC15 
                 GSTP1 
                 MT3 
                 MYO1C 
                 LRRTM1 
                 NIPA1 
                 BPIFA1 
                 SYNGR1 
                 HOXB8 
                 SETD7 
               
               
                 SCUBE2 
                 CKB 
                 RFX4 
                 BAIAP2L1 
                 CTU1 
                 GALK2 
                 MUC21 
                 KAZN 
                 ASRGL1 
                 TM9SF4 
               
               
                 TFAP2B 
                 BMP2 
                 MLC1 
                 JUP 
                 UPK3B 
                 TOM1 
                 TBX4 
                 PPT2 
                 FOXJ1 
                 MFSD1 
               
               
                 GFRA1 
                 BIN1 
                 HEPACAM 
                 FAM83H 
                 KLK7 
                 AHR 
                 LPCAT1 
                 PTMS 
                 CCDC114 
                 RAB8B 
               
               
                 TFAP2B 
                 BIN1 
                 MLC1 
                 SPINT2 
                 KLK7 
                 CALCOCO2 
                 MUC21 
                 SOX9 
                 CCDC114 
                 FKBP5 
               
               
                 STC2 
                 PFKP 
                 HEPACAM 
                 KRT8 
                 MAMSTR 
                 GALK2 
                 MBIP 
                 GTF2F1 
                 HOXB8 
                 MFSD1 
               
               
                 GFRA1 
                 HADHA 
                 MLC1 
                 LTBR 
                 LRRTM1 
                 USP47 
                 SCGB3A1 
                 KAZN 
                 CCDC114 
                 MAF 
               
               
                 TFAP2B 
                 CAPN5 
                 AQP4 
                 DDX5 
                 LRRTM1 
                 CAMK2D 
                 MBIP 
                 ITPK1 
                 FOXJ1 
                 FKBP5 
               
               
                 TBC1D9 
                 LAMC1 
                 SCRG1 
                 LTBR 
                 UPK3B 
                 DNAJC7 
                 PIP5KL1 
                 KAZN 
                 ELP3 
                 TM9SF4 
               
               
                 PLEKHF2 
                 UBE2E3 
                 FOXG1 
                 KRT8 
                 FGF18 
                 HARS2 
                 MBIP 
                 ERF 
                 FOXJ1 
                 ELL2 
               
               
                 GFRA1 
                 CKB 
                 AQP4 
                 SPINT2 
                 FGF18 
                 CAMK2D 
                 PIP5KL1 
                 LDLRAD3 
                 HOXB8 
                 FBXL3 
               
               
                 PLEKHF2 
                 PFKP 
                 SCRG1 
                 STAT6 
                 FGF18 
                 TMEM181 
                 SCGB3A1 
                 LDLRAD3 
                 C20orf85 
                 ELL2 
               
               
                 ESR1 
                 LAMC1 
                 FOXG1 
                 BRD3 
                 RPL17 
                 CALCOCO2 
                 COL6A5 
                 PSPN 
                 C20orf85 
                 MAF 
               
               
                 ESR1 
                 EIF3L 
                 FOXG1 
                 KRT18 
                 CLDN16 
                 CAMK2D 
                 XKRX 
                 TLN2 
                 C20orf85 
                 TBC1D2B 
               
               
                 SCUBE2 
                 ID1 
                 SCRG1 
                 SPINT2 
                 CLDN16 
                 RETSAT 
                 SCGB3A1 
                 SOX9 
                 ELP3 
                 MFSD1 
               
               
                 STC2 
                 LAMC1 
                 ST8SIA5 
                 NT5DC1 
                 IMPG2 
                 SLC38A9 
                 C16orf89 
                 TLN2 
                 CCDC33 
                 CHRNE 
               
               
                 SCUBE2 
                 ETFB 
                 AQP4 
                 KRT18 
                 CTCFL 
                 AHRR 
                 CXCL17 
                 ITPK1 
                 CCDC33 
                 ARHGEF33 
               
               
                 AZGP1 
                 ETFB 
                 BAALC 
                 B4GALT1 
                 CLDN16 
                 USP47 
                 C16orf89 
                 GTF2F1 
                 CCDC33 
                 ZNF519 
               
               
                 AZGP1 
                 ESRRA 
                 ST8SIA5 
                 KRT18 
                 RPL17 
                 DNAJC3 
                 C16orf89 
                 STK11 
                 TEKT4 
                 WDR44 
               
               
                 AZGP1 
                 CAPN5 
                 BAALC 
                 CNDP2 
                 IMPG2 
                 CHIC1 
                 CXCL17 
                 GTF2F1 
                 TEKT4 
                 RAB8B 
               
               
                 STC2 
                 PITPNM1 
                 KCNIP1 
                 KRT8 
                 CTCFL 
                 TNFRSF4 
                 CXCL17 
                 WIZ 
                 TEKT4 
                 TUBD1 
               
               
                 DCAF10 
                 SSBP1 
                 KCNIP1 
                 PERP 
                 MAMSTR 
                 HARS2 
                 COL6A5 
                 IL24 
                 WFDC2 
                 USP22 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 KIRC 
                 HNSC 
                 LGG 
                 THCA 
                 LUSC 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 KIRC_1 
                 KIRC_2 
                 HNSC_1 
                 HNSC_2 
                 LGG_1 
                 LGG_2 
                 THCA_1 
                 THCA_2 
                 LUSC_1 
                 LUSC_2 
               
               
                   
               
               
                 TLR3 
                 SMARCD2 
                 ALOXE3 
                 ACP6 
                 KCNJ10 
                 ANXA2 
                 TG 
                 RPN2 
                 SFTPA1 
                 SORBS2 
               
               
                 ENPP3 
                 FASN 
                 SDR9C7 
                 SVIP 
                 KCNJ10 
                 CLIC1 
                 TG 
                 PRKCSH 
                 EGFL6 
                 CXXC5 
               
               
                 TLR3 
                 RBM15B 
                 HEPHL1 
                 ACP6 
                 KCNJ10 
                 MYL12B 
                 TG 
                 YWHAG 
                 SFTPA1 
                 ME3 
               
               
                 SEMA5B 
                 FASN 
                 SDR9C7 
                 ACP6 
                 KCNJ9 
                 PDLIM1 
                 TPO 
                 PYCR1 
                 ABCA13 
                 KIF13B 
               
               
                 GAL3ST1 
                 GIPC1 
                 HEPHL1 
                 DDAH1 
                 CDH20 
                 OSTC 
                 TPO 
                 TMEM97 
                 SFTPA1 
                 FHIT 
               
               
                 SEMA5B 
                 SCAP 
                 HEPHL1 
                 ADCY6 
                 GPR37L1 
                 TAGLN2 
                 TPO 
                 METTL8 
                 ABCA13 
                 CXXC5 
               
               
                 TLR3 
                 FOXK2 
                 SDR9C7 
                 ICA1 
                 IL17D 
                 OSTC 
                 CRYGN 
                 RACGAP1 
                 ABCA13 
                 MAGI1 
               
               
                 ENPP3 
                 SMARCD2 
                 ALOXE3 
                 SVIP 
                 OLIG2 
                 CLIC1 
                 CRYGN 
                 TMEM97 
                 RASSF9 
                 CXXC5 
               
               
                 GAL3ST1 
                 SCAP 
                 KRTDAP 
                 SVIP 
                 OLIG1 
                 ANXA2 
                 CRYGN 
                 NUSAP1 
                 ABCC5 
                 PEBP1 
               
               
                 ENPP3 
                 HMGA1 
                 KRTDAP 
                 FN3K 
                 KCNJ9 
                 TEAD3 
                 IYD 
                 SCD 
                 RASSF9 
                 ALDH7A1 
               
               
                 GAL3ST1 
                 RANGAP1 
                 KRTDAP 
                 FARP1 
                 APC2 
                 TAGLN2 
                 DAPK2 
                 SCD 
                 RASSF9 
                 CRIP2 
               
               
                 ESM1 
                 SEC13 
                 FAM25A 
                 FN3K 
                 PSD2 
                 OSTC 
                 MUC15 
                 SCD 
                 TP63 
                 CST3 
               
               
                 SEC14L6 
                 HMGB3 
                 ALOXE3 
                 ICA1 
                 CDH20 
                 PPCS 
                 IYD 
                 IRAKI 
                 TP63 
                 PEBP1 
               
               
                 ESM1 
                 FASN 
                 SLC10A6 
                 ICA1 
                 PSD2 
                 MYL12A 
                 DAPK2 
                 IDH2 
                 ADH7 
                 KIF13B 
               
               
                 SEMA5B 
                 RANGAP1 
                 FAM25A 
                 PPP1R9A 
                 OLIG2 
                 ANXA2 
                 DAPK2 
                 MPZL1 
                 ADH7 
                 OASL 
               
               
                 MTCP1 
                 ARHGAP39 
                 SBSN 
                 FARP1 
                 OLIG1 
                 TAGLN2 
                 IYD 
                 IDH2 
                 EGFL6 
                 CRIP2 
               
               
                 ESM1 
                 SCAP 
                 IL36G 
                 FN3K 
                 CDH20 
                 PDLIM1 
                 MUC15 
                 IRAKI 
                 ADH7 
                 ALDH7A1 
               
               
                 CLEC18B 
                 ARHGAP39 
                 IL36G 
                 HNMT 
                 CACNG7 
                 CLIC1 
                 HHEX 
                 IRAKI 
                 ADAM23 
                 CRIP2 
               
               
                 SLC5A10 
                 BDH1 
                 CNFN 
                 PKN1 
                 KCNJ9 
                 F11R 
                 TCERG1L 
                 SLC6A8 
                 GPR87 
                 CAMK2N1 
               
               
                 ENPEP 
                 SEC13 
                 RNF222 
                 PPP1R9A 
                 PSD2 
                 S100A11 
                 HHEX 
                 IDH2 
                 TP63 
                 THRAP3 
               
               
                 CUBN 
                 GIPC1 
                 PLA2G4E 
                 HNMT 
                 MMD2 
                 TEAD3 
                 INPP5J 
                 PAICS 
                 FBXO27 
                 ALDH7A1 
               
               
                 ENPEP 
                 RANGAP1 
                 IL36RN 
                 HNMT 
                 APC2 
                 MYL12B 
                 HHEX 
                 PAICS 
                 ADAM23 
                 MGRN1 
               
               
                 MTCP1 
                 BDH1 
                 IL36RN 
                 DDAH1 
                 ZDHHC22 
                 PDLIM1 
                 MUC15 
                 PAICS 
                 NTS 
                 PLEKHA6 
               
               
                 ALPK2 
                 HMGA1 
                 SLC10A6 
                 ZNF253 
                 MMD2 
                 SERINC2 
                 SRL 
                 SLC6A8 
                 ADAM23 
                 MXD4 
               
               
                 SEC14L6 
                 HMGA1 
                 IL36G 
                 ZNF253 
                 TNR 
                 MYL12B 
                 SLC26A7 
                 SLC6A8 
                 GPR87 
                 PLEKHA6 
               
               
                 CLEC18B 
                 BDH1 
                 SBSN 
                 PKN1 
                 OLIG2 
                 S100A11 
                 INPP5J 
                 MPZL1 
                 B3GNT5 
                 PNPLA2 
               
               
                 SLC5A10 
                 HMGB3 
                 CNFN 
                 PATZ1 
                 RFX4 
                 S100A11 
                 LCN12 
                 DNPEP 
                 ABCC5 
                 GDI2 
               
               
                 ALPK2 
                 GNL3 
                 IL36RN 
                 ADCY6 
                 IL17D 
                 PPCS 
                 TCERG1L 
                 UCK2 
                 FBXO27 
                 PNPLA2 
               
               
                 CUBN 
                 MAVS 
                 BNC1 
                 IVD 
                 MMD2 
                 TES 
                 TCERG1L 
                 FAM189B 
                 EGFL6 
                 MAGI1 
               
               
                 CD70 
                 HMGB3 
                 SBSN 
                 IVD 
                 ZDHHC22 
                 MYO1C 
                 MGAT4C 
                 ARHGEF9 
                 NTS 
                 PNPLA2 
               
               
                 ALPK2 
                 FOXK2 
                 DSG1 
                 DDAH1 
                 GPR37L1 
                 MYL12A 
                 WDR86 
                 FAM189B 
                 GPR87 
                 KIF13B 
               
               
                 CUBN 
                 SMARCD2 
                 CNFN 
                 FARP1 
                 RFX4 
                 MYL12A 
                 INPP5J 
                 KIAA0930 
                 ABCC5 
                 CST3 
               
               
                 COL23A1 
                 GIPC1 
                 PLA2G4E 
                 ADCY6 
                 TNR 
                 WBP11 
                 SLC26A7 
                 TMEM97 
                 ARTN 
                 HDAC11 
               
               
                 SLC5A10 
                 RRP9 
                 FAM25A 
                 ZNF253 
                 ATP6V1G2 
                 MYO1C 
                 SLC26A7 
                 NUSAP1 
                 B3GNT5 
                 DDAH1 
               
               
                 ENPEP 
                 COX7A2L 
                 BNC1 
                 PKN1 
                 DSCAM 
                 TEAD3 
                 LCN12 
                 TTLL12 
                 NTS 
                 SORBS2 
               
               
                 TMEM72 
                 ARHGAP39 
                 DSG1 
                 TCTA 
                 IL17D 
                 MAP2K3 
                 ZCCHC12 
                 KIAA0930 
                 DSG3 
                 CAMK2N1 
               
               
                 CLEC18B 
                 ZMYND19 
                 BNC1 
                 PATZ1 
                 ATP6V1G2 
                 TMEM214 
                 SRL 
                 RACGAP1 
                 DSG3 
                 MGRN1 
               
               
                 SLC5A12 
                 ZNRF1 
                 PLA2G4E 
                 P4HTM 
                 ZDHHC22 
                 PPCS 
                 WDR86 
                 TTLL12 
                 ARTN 
                 MAGI1 
               
               
                 ZNF395 
                 EIF3E 
                 KRT75 
                 CHKA 
                 DSCAM 
                 MAP2K3 
                 SRL 
                 EIF4EBP1 
                 DSG3 
                 RNPEP 
               
               
                 COL23A1 
                 SEC13 
                 DSG1 
                 CRELD1 
                 ATP6V1G2 
                 ZDHHC5 
                 C2orf40 
                 TMCO3 
                 DCUN1D1 
                 MGRN1 
               
               
                 ASPA 
                 FOXK2 
                 SPRR2D 
                 P4HTM 
                 CMTM5 
                 LTBR 
                 ZBED2 
                 TTLL12 
                 ARTN 
                 SDSL 
               
               
                 SLC5A12 
                 ZMYND19 
                 DSG3 
                 GNB1 
                 DSCAM 
                 MYO1C 
                 LCN12 
                 KIAA0930 
                 GCLC 
                 CST3 
               
               
                 SLC5A12 
                 DOLPP1 
                 SLC10A6 
                 PPP1R9A 
                 TNR 
                 TMEM214 
                 C2orf40 
                 DNPEP 
                 PTHLH 
                 CAMK2N1 
               
               
                 SLC22A2 
                 DOLPP1 
                 FAM83C 
                 P4HTM 
                 CMTM5 
                 MAP2K3 
                 S100A5 
                 NUSAP1 
                 GCLC 
                 PEBP1 
               
               
                 TMEM72 
                 PWWP2B 
                 SPRR2D 
                 PATZ1 
                 CACNG7 
                 TMEM214 
                 WDR86 
                 MRPL16 
                 PTHLH 
                 RPS27L 
               
               
                 ASPA 
                 KIF22 
                 KRT75 
                 TMEM8B 
                 RFX4 
                 VAMP8 
                 TMEM233 
                 EIF4EBP1 
                 KRT74 
                 RAPSN 
               
               
                 SLC22A2 
                 ZMYND19 
                 NIPAL4 
                 SCCPDH 
                 CACNG7 
                 PRKAG1 
                 NKX2-1 
                 YWHAG 
                 FBXO27 
                 HDAC11 
               
               
                 SLC22A2 
                 RRP9 
                 SPRR2D 
                 MGAT4A 
                 CMTM5 
                 VAMP8 
                 C2orf40 
                 FAM189B 
                 B3GNT5 
                 RPS27L 
               
               
                 SEC14L6 
                 ZNRF1 
                 FGFBP1 
                 GORASP2 
                 OLIG1 
                 STAT6 
                 ZCCHC12 
                 YWHAG 
                 PTHLH 
                 PGPEP1 
               
               
                 COL23A1 
                 DYNLRB1 
                 KRT75 
                 PGPEP1 
                 CRB1 
                 LTBR 
                 ZCCHC12 
                 ATAD1 
                 WDR53 
                 HDAC11 
               
               
                 CD70 
                 RRP9 
                 FGFBP1 
                 IVD 
                 CRB1 
                 TBCCD1 
                 SLC26A4 
                 TMCO3 
                 SOST 
                 KIF9 
               
               
                 SLC17A3 
                 KIF22 
                 SPRR1B 
                 GORASP2 
                 GPR37L1 
                 JUP 
                 SLC26A4 
                 PYCR1 
                 SOST 
                 BTD 
               
               
                 TMEM174 
                 PACRG 
                 KRT16 
                 GNB1 
                 PMP2 
                 WBP11 
                 ZBED2 
                 MPZL1 
                 SOST 
                 SDSL 
               
               
                 ASPA 
                 GNL3 
                 FGFBP1 
                 THRAP3 
                 SHISA7 
                 LTBR 
                 ZBED2 
                 DNPEP 
                 TBCCD1 
                 RUFY1 
               
               
                 CD70 
                 KIF22 
                 DSG3 
                 CHCHD2 
                 CRB1 
                 TES 
                 S100A5 
                 NUDT2 
                 ACTL6A 
                 THRAP3 
               
               
                 TMEM174 
                 CCDC151 
                 IVL 
                 SCCPDH 
                 PMP2 
                 CDC25B 
                 TMEM233 
                 RACGAP1 
                 DCUN1D1 
                 MXD4 
               
               
                 SLC6A13 
                 RBM15B 
                 DSG3 
                 THRAP3 
                 PMP2 
                 STAT6 
                 CITED1 
                 TMCO3 
                 LSG1 
                 WIPI2 
               
               
                 SLC17A3 
                 RBM15B 
                 FAM83C 
                 SCCPDH 
                 NCAN 
                 JUP 
                 RXRG 
                 UCK2 
                 LSG1 
                 THRAP3 
               
               
                 SLC17A3 
                 GNL3 
                 SPRR1B 
                 CHCHD2 
                 SHISA7 
                 FBXL15 
                 RXRG 
                 MRPL16 
                 TBCCD1 
                 RPS27L 
               
               
                 SLC6A13 
                 ZNRF1 
                 SPRR1B 
                 THRAP3 
                 NCAN 
                 CDC25B 
                 CITED1 
                 PYCR1 
                 GCLC 
                 GDI2 
               
               
                 TMEM72 
                 PYCR1 
                 TGM1 
                 TCTA 
                 GFAP 
                 JUP 
                 TMEM233 
                 UCK2 
                 KRT74 
                 ADAM11 
               
               
                 MTCP1 
                 PWWP2B 
                 FAM83C 
                 CHKA 
                 LRRTM3 
                 TES 
                 SLC26A4 
                 UCHL5 
                 DCUN1D1 
                 DDAH1 
               
               
                 TMEM174 
                 CNKSR1 
                 GSDMC 
                 CHKA 
                 GFAP 
                 STAT6 
                 RXRG 
                 UCHL5 
                 PARL 
                 WIPI2 
               
               
                 NAT8 
                 TXN2 
                 TGM1 
                 TMEM39A 
                 NCAN 
                 ZDHHC5 
                 NKX2-1 
                 VWA1 
                 WDR53 
                 BTD 
               
               
                 SLC6A13 
                 ZADH2 
                 GSDMC 
                 MGAT4A 
                 GFAP 
                 B4GALT1 
                 MGAT4C 
                 ATAD1 
                 PARL 
                 MXD4 
               
               
                 SLC3A1 
                 COX7A2L 
                 TGM1 
                 CRELD1 
                 SHISA7 
                 SERINC2 
                 CITED1 
                 MRPL16 
                 ACTL6A 
                 RPS10 
               
               
                 SLC3A1 
                 MAVS 
                 GSDMC 
                 TCTA 
                 PCDH15 
                 SERINC2 
                 GABRB2 
                 ARHGEF9 
                 TBCCD1 
                 PGPEP1 
               
               
                 SLC3A1 
                 DYNLRB1 
                 NIPAL4 
                 CRELD1 
                 LRRTM3 
                 F11R 
                 MGAT4C 
                 UCHL5 
                 WDR53 
                 PLEKHA6 
               
               
                 NAT8 
                 FGFRL1 
                 KRT16 
                 CHCHD2 
                 APC2 
                 WBP11 
                 S100A5 
                 EIF4EBP1 
                 KRT74 
                 KIF9 
               
               
                 NAT8 
                 COX7A2L 
                 IVL 
                 GORASP2 
                 PCDH15 
                 B4GALT1 
                 NKX2-1 
                 SP3 
                 ACTL6A 
                 RNPEP 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 PRAD 
                 SKCM 
                 COAD 
                 STAD 
                 BLCA 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 PRAD_1 
                 PRAD_2 
                 SKCM_1 
                 SKCM_2 
                 COAD_1 
                 COAD_2 
                 STAD_1 
                 STAD_2 
                 BLCA_1 
                 BLCA_2 
               
               
                   
               
               
                 NKX3-1 
                 TAGLN2 
                 MLANA 
                 TOR1AIP1 
                 NOX1 
                 ZNF362 
                 ZFPM1 
                 B3GAT3 
                 UPK2 
                 ALDH7A1 
               
               
                 KLK3 
                 TAGLN2 
                 MLANA 
                 VOPP1 
                 CDX2 
                 PACS1 
                 ZFPM1 
                 CD2BP2 
                 UPK2 
                 NEO1 
               
               
                 KLK3 
                 LASP1 
                 MLANA 
                 MYO6 
                 NOX1 
                 TCEA2 
                 ZFPM1 
                 UROD 
                 UPK2 
                 ST6GAL1 
               
               
                 SLC45A3 
                 LASP1 
                 PAX3 
                 PBX1 
                 NOX1 
                 BCAM 
                 ZBTB7A 
                 PRDX5 
                 PLA2G2F 
                 ALDH2 
               
               
                 NKX3-1 
                 LASP1 
                 SLC45A2 
                 DDAH1 
                 CDX1 
                 PACS1 
                 GATA4 
                 UROD 
                 UPK1A 
                 ST6GAL1 
               
               
                 KLK3 
                 INTS1 
                 PMEL 
                 TMSB4X 
                 CDX2 
                 TRIM56 
                 ZBTB7A 
                 MRFAP1 
                 UPK1A 
                 HIPK2 
               
               
                 ACPP 
                 TAGLN2 
                 DCT 
                 MYO6 
                 CDX2 
                 ZC3H3 
                 GATA6 
                 TMEM9 
                 UPK1A 
                 SH3BP4 
               
               
                 ACPP 
                 OGDH 
                 TRPM1 
                 DDAH1 
                 GPA33 
                 PACS1 
                 GATA4 
                 TMEM9 
                 PLA2G2F 
                 STXBP1 
               
               
                 ACPP 
                 INTS1 
                 TRPM1 
                 PBX1 
                 GPA33 
                 ZC3H3 
                 GATA4 
                 DNAJB2 
                 VGLL1 
                 NFIX 
               
               
                 SLC45A3 
                 YWHAH 
                 TRPM1 
                 RAB3IP 
                 CCL24 
                 C20orf194 
                 GNL3L 
                 TSR2 
                 PLA2G2F 
                 CERK 
               
               
                 NKX3-1 
                 KIAA0100 
                 PMEL 
                 PTPRF 
                 GPA33 
                 CLU 
                 GATA6 
                 UBXN6 
                 SNX31 
                 CERK 
               
               
                 SLC45A3 
                 OGDH 
                 PAX3 
                 NFYB 
                 CDX1 
                 BCAM 
                 ZBTB7A 
                 RNF187 
                 VGLL1 
                 ST6GAL1 
               
               
                 CHRNA2 
                 TNFAIP8L1 
                 DCT 
                 VOPP1 
                 CDX1 
                 ZC3H3 
                 ZBTB20 
                 RNF215 
                 PPARG 
                 ALDH2 
               
               
                 KLK4 
                 OGDH 
                 PAX3 
                 VOPP1 
                 CCL24 
                 TCEA2 
                 GATA6 
                 CD2BP2 
                 SNX31 
                 SH3BP4 
               
               
                 CHRNA2 
                 OSBPL3 
                 DCT 
                 PBX1 
                 CDH17 
                 CLU 
                 GNL3L 
                 FN3KRP 
                 SNX31 
                 OAT 
               
               
                 OR51E2 
                 OSBPL3 
                 SLC45A2 
                 PAWR 
                 CCL24 
                 KRBA1 
                 GNL3L 
                 ADPRHL2 
                 VGLL1 
                 OAT 
               
               
                 CHRNA2 
                 CIT 
                 SLC45A2 
                 NET1 
                 MEPIA 
                 SMARCA1 
                 CLDN18 
                 CIRBP 
                 PM20D1 
                 PARD3B 
               
               
                 KLK4 
                 YWHAH 
                 PMEL 
                 NET1 
                 GUCY2C 
                 BCAM 
                 CLDN18 
                 PRDX5 
                 UPK3A 
                 IQGAP2 
               
               
                 OR51E2 
                 TNFAIP8L1 
                 C10orf90 
                 DDAH1 
                 EPS8L3 
                 CLU 
                 CLDN18 
                 DNAJB2 
                 PM20D1 
                 STXBP1 
               
               
                 KLK4 
                 LAPTM4B 
                 C10orf90 
                 MAGI1 
                 GUCY2C 
                 NR3C1 
                 ZBTB20 
                 TMED1 
                 ACER2 
                 PTPRJ 
               
               
                 OR51E2 
                 CIT 
                 C10orf90 
                 RAB3IP 
                 GUCY2C 
                 MYH10 
                 NKX6-3 
                 TMED1 
                 BTBD16 
                 CERK 
               
               
                 SLC30A4 
                 ANP32E 
                 ALX1 
                 RAB3IP 
                 MEPIA 
                 TCEA2 
                 ZBTB20 
                 MYL6B 
                 UPK3A 
                 COBL 
               
               
                 HOXB13 
                 YWHAH 
                 ALX1 
                 SGMS1 
                 MEPIA 
                 ABHD8 
                 NKX6-3 
                 RNF215 
                 UPK3B 
                 NFIX 
               
               
                 SLC30A4 
                 FAM49B 
                 C19orf71 
                 SGMS1 
                 CDH17 
                 OST4 
                 CCDC68 
                 HSDL1 
                 BTBD16 
                 COBL 
               
               
                 HOXB13 
                 INTS1 
                 ALX1 
                 NFYB 
                 PHGR1 
                 BCL6 
                 ONECUT2 
                 DNAJB2 
                 BTBD16 
                 RAPGEF5 
               
               
                 HOXB13 
                 KIAA0100 
                 TYRP1 
                 SLC38A1 
                 PHGR1 
                 ZNF362 
                 NKX6-3 
                 HSDL1 
                 PM20D1 
                 COBL 
               
               
                 ANO7 
                 SERPINB1 
                 FCRLA 
                 SLC38A1 
                 PHGR1 
                 PTPRS 
                 CCDC68 
                 COQ5 
                 ACER2 
                 HIPK2 
               
               
                 SLC30A4 
                 LAPTM4B 
                 TYRP1 
                 PTPRF 
                 CDH17 
                 TRIM56 
                 ONECUT2 
                 UROD 
                 UPK3B 
                 NFIC 
               
               
                 ANO7 
                 S100A16 
                 TYRP1 
                 TJP2 
                 MYO1A 
                 BCL6 
                 PABPC3 
                 TMED1 
                 GRHL3 
                 KLF13 
               
               
                 TRPV6 
                 S100A16 
                 TRIM63 
                 OCIAD2 
                 NR1I2 
                 NR3C1 
                 ONECUT2 
                 TMEM9 
                 SNCG 
                 NFIC 
               
               
                 ANO7 
                 CDC25B 
                 CAPN3 
                 SGMS1 
                 NR1I2 
                 SMARCA1 
                 CCDC68 
                 MYL6B 
                 ACER2 
                 AGAP1 
               
               
                 BEND4 
                 CIT 
                 C19orf71 
                 MAGI1 
                 MYO1A 
                 NR3C1 
                 ONECUT3 
                 B3GAT3 
                 UPK3A 
                 NFIX 
               
               
                 FOLH1 
                 LAPTM4B 
                 CAPN3 
                 MAGI1 
                 ATOH1 
                 KRBA1 
                 MUC13 
                 PRDX5 
                 ACOXL 
                 IQGAP2 
               
               
                 BEND4 
                 OSBPL3 
                 TRIM63 
                 TJP2 
                 ATOH1 
                 LDOC1 
                 ONECUT3 
                 MYL6B 
                 GDPD3 
                 ALDH2 
               
               
                 TMEFF2 
                 FSCN1 
                 IRF4 
                 PTPRF 
                 DPEP1 
                 OBSL1 
                 ONECUT3 
                 ADPRHL2 
                 UPK3B 
                 SH3BP4 
               
               
                 BEND4 
                 FSCN1 
                 TSPAN10 
                 TJP2 
                 PPP1R14D 
                 BCL6 
                 C6orf222 
                 APOBR 
                 ACOXL 
                 PTPRJ 
               
               
                 NWD1 
                 ANP32E 
                 TRIM63 
                 PAWR 
                 MYO1A 
                 SMARCA1 
                 TFF2 
                 ING4 
                 PPARG 
                 KLF13 
               
               
                 NWD1 
                 ARHGEF2 
                 IRF4 
                 SPINT2 
                 ISX 
                 TMEM25 
                 REG4 
                 B3GAT3 
                 IL9R 
                 SYBU 
               
               
                 CHRM1 
                 FSCN1 
                 CAPN3 
                 MYO6 
                 BCL2L14 
                 AMOTL1 
                 REG4 
                 RNF215 
                 NIPAL4 
                 KLF13 
               
               
                 TRPV6 
                 CTSC 
                 IRF4 
                 SLC38A1 
                 ASCL2 
                 PTPRS 
                 REG4 
                 ING4 
                 ACOXL 
                 STXBP1 
               
               
                 FOLH1 
                 S100A16 
                 TSPAN10 
                 NET1 
                 BCL2L14 
                 C20orf194 
                 CTSE 
                 MRFAP1 
                 IL9R 
                 IQGAP2 
               
               
                 FOLH1 
                 ANP32E 
                 FOXD3 
                 NFYB 
                 SLC26A3 
                 C20orf194 
                 CTSE 
                 CIRBP 
                 PPARG 
                 GSE1 
               
               
                 CHRM1 
                 CERK 
                 FCRLA 
                 PTPRK 
                 ATOH1 
                 TMEM25 
                 MUC5AC 
                 CD2BP2 
                 IL9R 
                 RASGEF1B 
               
               
                 ADRB1 
                 C1GALT1 
                 ENTHD1 
                 RBM47 
                 SLC26A3 
                 TMEM25 
                 VSIG1 
                 ZMAT2 
                 OR13A1 
                 SYBU 
               
               
                 TMEFF2 
                 ARHGEF2 
                 TSPAN10 
                 PSD4 
                 ISX 
                 LDOC1 
                 TFF2 
                 COQ5 
                 PSCA 
                 NFIC 
               
               
                 ZNF613 
                 AGPS 
                 MMP8 
                 EPCAM 
                 DPEP1 
                 MYH10 
                 TFF2 
                 HSDL1 
                 GRHL3 
                 OAT 
               
               
                 TRPV6 
                 ARHGEF2 
                 ENTHD1 
                 CDS1 
                 BCL2L14 
                 PTPRS 
                 MUC5AC 
                 ADPRHL2 
                 SNCG 
                 PHC2 
               
               
                 ZNF613 
                 CDC25B 
                 FCRLA 
                 PSD4 
                 ASCL2 
                 EVL 
                 MUC5AC 
                 GMPR2 
                 FCRLB 
                 PTPRJ 
               
               
                 OR51E1 
                 TNFAIP8L1 
                 MMP8 
                 CDS1 
                 SLC26A3 
                 KRBA1 
                 MUC13 
                 UBXN6 
                 SNCG 
                 PBXIP1 
               
               
                 CHRM1 
                 CDC25B 
                 EXTL1 
                 PTPRK 
                 ISX 
                 ABHD8 
                 CTSE 
                 UBXN6 
                 GDPD3 
                 GSE1 
               
               
                 LMAN1L 
                 RELT 
                 GPR143 
                 OCIAD2 
                 GPR35 
                 RDX 
                 VSIG1 
                 ING4 
                 GDPD3 
                 HIPK2 
               
               
                 ZNF613 
                 DERA 
                 SNCA 
                 PFN2 
                 EPS8L3 
                 TRIM56 
                 C6orf222 
                 COQ5 
                 PSCA 
                 SLC25A23 
               
               
                 ADRB1 
                 RHBDF2 
                 FOXD3 
                 SPINT2 
                 NR1I2 
                 RDX 
                 PDX1 
                 APOBR 
                 FCRLB 
                 RASGEF1B 
               
               
                 ADRB1 
                 DERA 
                 ENTHD1 
                 PAWR 
                 GPR35 
                 EVL 
                 MUC13 
                 CIRBP 
                 OR13A1 
                 RASGEF1B 
               
               
                 STEAP2 
                 KIAA0100 
                 MMP8 
                 RBM47 
                 PPP1R14D 
                 EVL 
                 VSIG1 
                 TSR2 
                 PSCA 
                 GSE1 
               
               
                 NWD1 
                 AGPS 
                 GPR143 
                 USP39 
                 PPP1R14D 
                 RDX 
                 C6orf222 
                 TSR2 
                 SYT8 
                 SLC25A23 
               
               
                 MSMB 
                 CTSC 
                 GPR143 
                 SPINT2 
                 ASCL2 
                 ZNF362 
                 TM4SF20 
                 APOBR 
                 NIPAL4 
                 RAPGEF5 
               
               
                 OR51E1 
                 RHBDF2 
                 EXTL1 
                 BTBD1 
                 GPR35 
                 OBSL1 
                 TM4SF20 
                 F10 
                 FCRLB 
                 ALDH7A1 
               
               
                 MSMB 
                 SERPINB1 
                 MMP17 
                 USP39 
                 KRT20 
                 AMOTL1 
                 PGC 
                 MRFAP1 
                 TMEM40 
                 RAPGEF5 
               
               
                 LMAN1L 
                 GHRL 
                 FOXD3 
                 OCIAD2 
                 KRT20 
                 TUSC3 
                 PGC 
                 SNX17 
                 PADI3 
                 UTRN 
               
               
                 DNASE2B 
                 RELT 
                 CA14 
                 PTPRK 
                 KRT20 
                 OBSL1 
                 PGC 
                 ZMAT2 
                 SYT8 
                 ALDH7A1 
               
               
                 OR51E1 
                 AGPS 
                 SNCA 
                 BTBD1 
                 DPEP1 
                 BNIP3 
                 TM4SF20 
                 SLC25A34 
                 SYT8 
                 UTRN 
               
               
                 MSMB 
                 KPNA2 
                 EXTL1 
                 USP39 
                 FAM3D 
                 AMOTL1 
                 PDX1 
                 UCK1 
                 PADI3 
                 ATXN1 
               
               
                 TMEFF2 
                 CLCN6 
                 CA14 
                 CFL2 
                 VIL1 
                 OST4 
                 GJD3 
                 SLC25A34 
                 NIPAL4 
                 ATXN1 
               
               
                 POTEH 
                 GHRL 
                 MMP17 
                 BTBD1 
                 FAM3D 
                 MYH10 
                 PDX1 
                 SLC25A34 
                 GRHL3 
                 UTRN 
               
               
                 DNASE2B 
                 ST6GALNAC4 
                 SNCA 
                 TOR1AIP1 
                 EPS8L3 
                 OST4 
                 POTEE 
                 PAK6 
                 TMEM40 
                 ATXN1 
               
               
                 LMAN1L 
                 HS3ST2 
                 ABCB5 
                 RBM47 
                 ATP10B 
                 GALNT1 
                 GJD3 
                 TTLL10 
                 UPK1B 
                 SLC25A23 
               
               
                 STEAP2 
                 TXLNA 
                 CA14 
                 TOR1AIP1 
                 ATP10B 
                 FMRI 
                 GJD3 
                 PAK6 
                 PADI3 
                 SMARCA5 
               
               
                 POTEH 
                 RELT 
                 MMP17 
                 CCDC12 
                 FAM3D 
                 TUSC3 
                 POTEE 
                 TTLL10 
                 UPK1B 
                 NEO1 
               
               
                 STEAP2 
                 LIMA1 
                 ABCB5 
                 PSD4 
                 ATP10B 
                 AKIRIN1 
                 POTEE 
                 LRRC8E 
                 TNNI2 
                 SYBU 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 LIHC 
                 CESC 
                 KIRP 
                 SARC 
                 ESCA 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 LIHC_1 
                 LIHC_2 
                 CESC_1 
                 CESC_2 
                 KIRP_1 
                 KIRP_2 
                 SARC_1 
                 SARC_2 
                 ESCA_1 
                 ESCA_2 
               
               
                   
               
               
                 C8B 
                 IGF1R 
                 ARHGEF33 
                 ZNF608 
                 LRRN4 
                 EMP2 
                 TWIST2 
                 ERBB3 
                 ANKRD11 
                 CD63 
               
               
                 SERPINC1 
                 FAR1 
                 SYCP2 
                 INSR 
                 KCP 
                 NOTCH3 
                 TWIST2 
                 DSP 
                 ZBTB7A 
                 APH1A 
               
               
                 C8B 
                 FAR1 
                 ARHGEF33 
                 ZNF773 
                 LRRN4 
                 TP53I11 
                 TWIST2 
                 FAM83H 
                 ANKRD11 
                 CD81 
               
               
                 SERPINC1 
                 EXOC1 
                 SYCP2 
                 TBC1D16 
                 SMTNL2 
                 TP53I11 
                 C1QTNF2 
                 RAB11FIP4 
                 ZBTB7A 
                 PEBP1 
               
               
                 ASGR2 
                 MAPRE1 
                 KCNS1 
                 PTPRM 
                 LRRN4 
                 NOTCH3 
                 FAM180A 
                 ERBB3 
                 ZBTB7A 
                 PPIB 
               
               
                 C8B 
                 CTBP2 
                 CDKN2A 
                 GRINA 
                 TPK1 
                 UAP1 
                 RAB23 
                 TPD52 
                 EIF3C 
                 NUDT16L1 
               
               
                 SERPINC1 
                 SLC25A36 
                 ARHGEF33 
                 ZC4H2 
                 PKHD1 
                 NOTCH3 
                 IL17B 
                 CAMSAP3 
                 RC3H1 
                 UFC1 
               
               
                 APOC3 
                 IQGAP1 
                 SYCP2 
                 CREB3L2 
                 LYG1 
                 TP53I11 
                 FAM180A 
                 WWC1 
                 FBRSL1 
                 PEBP1 
               
               
                 ASGR1 
                 HK1 
                 KCNS1 
                 PKIG 
                 SMTNL2 
                 EMP2 
                 CCDC36 
                 CAMSAP3 
                 FBRSL1 
                 APH1A 
               
               
                 KNG1 
                 HK1 
                 ZNF541 
                 PTPRM 
                 SMTNL2 
                 MFGE8 
                 CDK15 
                 ERBB3 
                 GNL3L 
                 TSR2 
               
               
                 CPB2 
                 HK1 
                 KCNS1 
                 PTPRG 
                 TPK1 
                 ZDHHC20 
                 C1QTNF2 
                 PRKCZ 
                 FBXL18 
                 NUDT16L1 
               
               
                 C8A 
                 SLC25A12 
                 RIBC2 
                 PKIG 
                 MYL3 
                 DPYSL3 
                 SHOX2 
                 TPD52 
                 RC3H1 
                 ANP32A 
               
               
                 AGXT 
                 FAR1 
                 EPHX3 
                 CCND1 
                 TPK1 
                 EMP2 
                 CDK15 
                 CAMSAP3 
                 GNL3L 
                 TEX264 
               
               
                 AGXT 
                 SLC25A36 
                 ZNF541 
                 MOCS1 
                 LYG1 
                 NEURL1B 
                 C1QTNF2 
                 FAM84B 
                 EIF3C 
                 ING4 
               
               
                 ASGR1 
                 TBC1D10B 
                 RIBC2 
                 ZBTB10 
                 PTH1R 
                 MFGE8 
                 FAM180A 
                 RAB11FIP4 
                 RC3H1 
                 TMEM9 
               
               
                 ASGR2 
                 PLEKHB2 
                 ZNF541 
                 TMEM150A 
                 MYL3 
                 COL5A3 
                 TWIST1 
                 TPD52 
                 ANKRD11 
                 MRFAP1 
               
               
                 AGXT 
                 ABR 
                 RIBC2 
                 PTPRM 
                 EMX1 
                 NEURL1B 
                 MRGPRF 
                 LSR 
                 FBRSL1 
                 PPIB 
               
               
                 HAO1 
                 ZNF827 
                 SOX30 
                 ZNF608 
                 ENAM 
                 COL5A3 
                 CDK15 
                 MARVELD2 
                 HCFC1 
                 CD81 
               
               
                 ASGR1 
                 ABR 
                 C19orf57 
                 TBC1D16 
                 MYL3 
                 LTBP1 
                 IL17B 
                 MARVELD2 
                 NRARP 
                 ANP32A 
               
               
                 ITIH3 
                 IQGAP1 
                 SERPINB3 
                 CCND1 
                 KCP 
                 MFGE8 
                 TWIST1 
                 F11R 
                 MAPK6 
                 APH1A 
               
               
                 C8A 
                 ZNF827 
                 HMSD 
                 ZNF608 
                 EMX1 
                 UAP1 
                 CCDC36 
                 MARVELD2 
                 MAPK6 
                 PPIB 
               
               
                 APOC3 
                 PLEKHB2 
                 HMSD 
                 ZC4H2 
                 KCP 
                 MARCKSL1 
                 TWIST1 
                 DSP 
                 EIF3C 
                 STK16 
               
               
                 APOC3 
                 CHD3 
                 TAF7L 
                 ZNF773 
                 ENAM 
                 NEURL1B 
                 TBXA2R 
                 FAM84B 
                 NRARP 
                 ARF5 
               
               
                 APOA5 
                 ZNF827 
                 SOX30 
                 ZC4H2 
                 SYPL2 
                 UAP1 
                 CCDC36 
                 PRKCZ 
                 GNL3L 
                 PDHB 
               
               
                 F2 
                 IQGAP1 
                 PRDM15 
                 TBC1D16 
                 DYNC2LI1 
                 AZIN1 
                 TNFAIP8L3 
                 WWC1 
                 HCFC1 
                 CD63 
               
               
                 F2 
                 ARF3 
                 HMSD 
                 ZNF773 
                 DYNC2LI1 
                 SAE1 
                 TNFAIP8L3 
                 FAM84B 
                 FBXL18 
                 ING4 
               
               
                 ASGR2 
                 SLC44A2 
                 C19orf57 
                 PKIG 
                 PTH1R 
                 DPYSL3 
                 IL17B 
                 HOOK1 
                 KLHL11 
                 TMED1 
               
               
                 F2 
                 PLEKHB2 
                 TAF7L 
                 ZNF43 
                 ENAM 
                 LDLR 
                 MRGPRF 
                 SPINT2 
                 MAPK6 
                 MRFAP1 
               
               
                 HRG 
                 IGF1R 
                 C19orf57 
                 FERMT2 
                 COQ9 
                 SERP1 
                 EBF3 
                 DSP 
                 FBXL18 
                 STK16 
               
               
                 HRG 
                 SLC25A36 
                 TAF7L 
                 MOCS1 
                 EMX1 
                 PCDH1 
                 MRGPRF 
                 F11R 
                 PABPC3 
                 TMED1 
               
               
                 ITIH2 
                 CLSTN1 
                 EPHX3 
                 CREB3L2 
                 SYPL2 
                 PCDH1 
                 TBXA2R 
                 WWC1 
                 RBM15 
                 TSR2 
               
               
                 KNG1 
                 IGF1R 
                 IL20RB 
                 CCND1 
                 LYG1 
                 LTBP1 
                 ADAM33 
                 MYH14 
                 ATAD5 
                 ING4 
               
               
                 CPB2 
                 CTBP2 
                 CENPK 
                 PTPRG 
                 CYS1 
                 SERP1 
                 EBF3 
                 FAM83H 
                 CLSPN 
                 TSR2 
               
               
                 KNG1 
                 METTL9 
                 CDC7 
                 INSR 
                 PTH1R 
                 SAE1 
                 ADAM33 
                 LSR 
                 NRARP 
                 CD2BP2 
               
               
                 CPB2 
                 METTL9 
                 WDR76 
                 INSR 
                 SULT1C4 
                 AZIN1 
                 EBF3 
                 PRKCZ 
                 KLHL11 
                 GPANK1 
               
               
                 APOH 
                 CLSTN1 
                 RFC4 
                 AP2B1 
                 HOGA1 
                 SERINC5 
                 MFAP4 
                 PTPRF 
                 ZFPM1 
                 NUDT16L1 
               
               
                 C8G 
                 ABR 
                 MEI1 
                 FERMT2 
                 HOGA1 
                 SAE1 
                 ADAM33 
                 SPINT2 
                 RBM15 
                 PEX11B 
               
               
                 ITIH3 
                 CLSTN1 
                 SERPINB3 
                 GRINA 
                 DYNC2LI1 
                 SERP1 
                 SHOX2 
                 CXADR 
                 HCFC1 
                 ILF3 
               
               
                 ITIH2 
                 CCNI 
                 EPHX3 
                 SNX19 
                 SLC13A1 
                 COL5A3 
                 TNFAIP8L3 
                 RAB11FIP4 
                 CLSPN 
                 ELOF1 
               
               
                 ITIH2 
                 ARF3 
                 SOX30 
                 PARD3B 
                 SULT1C4 
                 DPYSL3 
                 SCARA5 
                 MYH14 
                 RBM15 
                 UROD 
               
               
                 ITIH3 
                 CHD3 
                 LY6K 
                 CREB3L2 
                 SYPL2 
                 SERINC5 
                 RAB23 
                 PTPRF 
                 ZFPM1 
                 PEX11B 
               
               
                 APOH 
                 MAPRE1 
                 MEI1 
                 TNS3 
                 HOGA1 
                 PCDH1 
                 LGI2 
                 LSR 
                 ATAD5 
                 UROD 
               
               
                 AMBP 
                 CCNI 
                 SERPINB3 
                 MTPN 
                 PKHD1 
                 AZIN1 
                 SHOX2 
                 MYH14 
                 FAM83B 
                 ZMAT2 
               
               
                 APOH 
                 ARF3 
                 MEI1 
                 SIAE 
                 CYS1 
                 MARCKSL1 
                 PTGFR 
                 MAL2 
                 CLSPN 
                 UROD 
               
               
                 HAO1 
                 SLC25A12 
                 IL20RB 
                 GRINA 
                 SLC13A1 
                 LTBP1 
                 HSPB6 
                 PTPRF 
                 ZFPM1 
                 STK16 
               
               
                 SERPINA10 
                 METTL9 
                 PSMC3IP 
                 TMEM150A 
                 CYS1 
                 BAZ2A 
                 LGI2 
                 CXADR 
                 ATAD5 
                 PEX11B 
               
               
                 HRG 
                 CTBP2 
                 LY6K 
                 ZBTB10 
                 SULT1C4 
                 MARCKSL1 
                 LGI2 
                 SPINT2 
                 FAM83B 
                 DNAJB2 
               
               
                 SERPINA10 
                 CHMP3 
                 CDC7 
                 PTPRG 
                 PKHD1 
                 BAZ2A 
                 SCARA5 
                 MAL2 
                 FAM83B 
                 ANP32A 
               
               
                 C8G 
                 SLC44A2 
                 WDR76 
                 SNX19 
                 SLC17A1 
                 SERINC5 
                 PTGFR 
                 CXADR 
                 REL 
                 PDHB 
               
               
                 C8G 
                 DCTN5 
                 CDKN2A 
                 TNS3 
                 SLC13A1 
                 PRRX1 
                 PTGFR 
                 CDH1 
                 REL 
                 TEX264 
               
               
                 SERPINA10 
                 PRKRA 
                 GPR87 
                 SNX19 
                 SLC17A1 
                 LDLR 
                 RAB23 
                 RNF11 
                 REL 
                 TMEM9 
               
               
                 APOC2 
                 SLC25A12 
                 LY6K 
                 FERMT2 
                 SLC17A1 
                 SLC22A23 
                 PTX3 
                 MAL2 
                 PABPC3 
                 GPANK1 
               
               
                 C8A 
                 MTMR2 
                 CDKN2A 
                 AP2B1 
                 SLCO4C1 
                 ZDHHC20 
                 TBXA2R 
                 CDH1 
                 TMPPE 
                 TMED1 
               
               
                 AHSG 
                 DCTN5 
                 WDR76 
                 TNS3 
                 PAX2 
                 ZDHHC20 
                 SCARA5 
                 FAM83H 
                 MXD1 
                 ARF5 
               
               
                 APOA2 
                 CCNI 
                 CENPK 
                 SIAE 
                 SLCO4C1 
                 BAZ2A 
                 EBF1 
                 F11R 
                 MXD1 
                 MRFAP1 
               
               
                 AHSG 
                 CHD3 
                 CENPK 
                 ZBTB10 
                 MIOX 
                 TSPAN13 
                 EBF1 
                 CTSO 
                 MXD1 
                 PARK7 
               
               
                 AHSG 
                 SLC44A2 
                 IL20RB 
                 AP2B1 
                 SLC3A1 
                 LDLR 
                 PTX3 
                 HOOK1 
                 GJD3 
                 SOWAHA 
               
               
                 HAO1 
                 MTMR2 
                 S1PR5 
                 SIAE 
                 SLCO4C1 
                 TSPAN13 
                 PTX3 
                 CDH1 
                 TMPPE 
                 GPANK1 
               
               
                 APOC2 
                 MTMR2 
                 GPR87 
                 MARVELD1 
                 PAX2 
                 TSPAN13 
                 SYDE1 
                 KRT18 
                 GJD3 
                 ATRIP 
               
               
                 APOA5 
                 C6orf203 
                 PSMC3IP 
                 MOCS1 
                 MIOX 
                 SQLE 
                 HSPA12B 
                 DDX54 
                 PABPC3 
                 SLC11A1 
               
               
                 APOA5 
                 EFCAB2 
                 KLHDC7B 
                 TMEM150A 
                 MIOX 
                 INTS7 
                 HSPB6 
                 KRT18 
                 GJD3 
                 NLRP14 
               
               
                 APOA2 
                 MAPRE1 
                 KLHDC7B 
                 MARVELD1 
                 PAX2 
                 BCL6 
                 EBF1 
                 RNF11 
                 POTEE 
                 ATRIP 
               
               
                 APOC2 
                 PRKRA 
                 CDC7 
                 CRY1 
                 CDH16 
                 PIH1D1 
                 HSPA12B 
                 UBN1 
                 KLHL11 
                 ZFYVE28 
               
               
                 VTN 
                 WBP2 
                 GPR87 
                 PRKCD 
                 SLC3A1 
                 SQLE 
                 MFAP4 
                 KRT18 
                 POTEE 
                 SOWAHA 
               
               
                 APOA2 
                 DCTN5 
                 KLHDC7B 
                 PRKCD 
                 SLC3A1 
                 PIH1D1 
                 HSPA12B 
                 MAP3K7 
                 PLEC 
                 CD63 
               
               
                 AMBP 
                 WBP2 
                 S1PR5 
                 ZNF43 
                 CDH16 
                 SQLE 
                 MFAP4 
                 KRT8 
                 POTEE 
                 WNT16 
               
               
                 ALB 
                 WBP2 
                 PSMC3IP 
                 EPDR1 
                 CDH16 
                 MTHFD2 
                 SYDE1 
                 KRT8 
                 PLEC 
                 CD81 
               
               
                 VTN 
                 CHMP3 
                 S1PR5 
                 EPDR1 
                 GLYAT 
                 BCL6 
                 HSPB6 
                 KRT8 
                 PLEC 
                 PEBP1 
               
               
                 VTN 
                 PRMT2 
                 RFC4 
                 FOXJ3 
                 GLYAT 
                 SLC22A23 
                 SYDE1 
                 SPINT1 
                 TMPPE 
                 ZFYVE28 
               
               
                 AMBP 
                 PRMT2 
                 CENPW 
                 PRKCD 
                 GLYAT 
                 ITGAL 
                 KANK2 
                 SPINT1 
                 C11orf91 
                 NLRP14 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 PAAD 
                 PCPG 
                 READ 
                 TCGT 
                 THYM_1 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 PAAD_1 
                 PAAD_2 
                 PCPG_1 
                 PCPG_2 
                 READ_1 
                 READ_2 
                 TGCT_1 
                 TGCT_2 
                 THYM_1 
                 THYM_2 
               
               
                   
               
               
                 GCG 
                 FOXRED2 
                 CHRNA3 
                 YBX1 
                 LY6G6D 
                 SNX24 
                 VRTN 
                 MFSD6 
                 PAX1 
                 DSTN 
               
               
                 GCG 
                 ORC3 
                 SLC18A1 
                 TMEM63A 
                 CDX2 
                 DTX3L 
                 LIN28A 
                 EFNA1 
                 PRSS16 
                 NCKAP1 
               
               
                 GCG 
                 MCUR1 
                 CHRNA3 
                 SERBP1 
                 CDX2 
                 NFIC 
                 LIN28A 
                 CHMP3 
                 PRSS16 
                 DSTN 
               
               
                 CPA1 
                 FOXRED2 
                 PHOX2A 
                 LSR 
                 LY6G6D 
                 KRBA1 
                 VRTN 
                 TICAM1 
                 PAX1 
                 NCKAP1 
               
               
                 CPA1 
                 MCUR1 
                 CHRNA3 
                 IDH2 
                 LY6G6D 
                 KCTD1 
                 LIN28A 
                 ELOVL1 
                 FOXN1 
                 DHCR24 
               
               
                 CPA1 
                 TMEM69 
                 TH 
                 ERBB2 
                 NOX1 
                 GPD2 
                 VRTN 
                 MBNL2 
                 PRSS16 
                 CALU 
               
               
                 G6PC2 
                 KCNAB1 
                 TH 
                 YBX1 
                 NOX1 
                 SS18 
                 DPPA4 
                 EXOC3 
                 PAX1 
                 CALU 
               
               
                 CLPS 
                 MMACHC 
                 TH 
                 ANXA11 
                 NOX1 
                 STOM 
                 DPPA4 
                 KLHDC10 
                 RAG1 
                 ZDHHC9 
               
               
                 CLPS 
                 SUV39H2 
                 PHOX2A 
                 NOTCH2 
                 CDX2 
                 STOM 
                 TRIM71 
                 IRF2BP2 
                 CHRM4 
                 CAMK2N1 
               
               
                 CLPS 
                 RFC5 
                 DBH 
                 KIF1C 
                 CCL24 
                 RNF144B 
                 TRIM71 
                 PGRMC1 
                 GRAP2 
                 DHCR24 
               
               
                 G6PC2 
                 L2HGDH 
                 DRD2 
                 IDH2 
                 GPA33 
                 NFIC 
                 DPPA4 
                 COMT 
                 CCR9 
                 CAMK2N1 
               
               
                 CPA2 
                 FOXRED2 
                 DBH 
                 IDH2 
                 CCL24 
                 C20orf194 
                 GDF3 
                 TICAM1 
                 SLC46A2 
                 EPS8 
               
               
                 CASR 
                 L2HGDH 
                 DBH 
                 ZFP36L1 
                 GPR35 
                 NFIC 
                 GDF3 
                 AIG1 
                 RAG1 
                 DHCR24 
               
               
                 G6PC2 
                 SUV39H2 
                 HAND2 
                 YBX1 
                 GPA33 
                 STOM 
                 GDF3 
                 EFNA1 
                 FOXN1 
                 NCKAP1 
               
               
                 CPA2 
                 RFC5 
                 SLC18A1 
                 TRAF4 
                 AIFM3 
                 EVL 
                 TRIM71 
                 PHC2 
                 RAG1 
                 SLC31A1 
               
               
                 CASR 
                 CLPB 
                 PHOX2A 
                 ERBB2 
                 GPA33 
                 DTX3L 
                 POU5F1 
                 TMEM59 
                 PTCRA 
                 PCDH1 
               
               
                 CASR 
                 CELSR2 
                 SLC18A1 
                 PTGFRN 
                 CCL24 
                 KCTD1 
                 POU5F1 
                 DAZAP2 
                 PTCRA 
                 SOX13 
               
               
                 CPA2 
                 TMEM69 
                 HAND2 
                 ZFP36L1 
                 AIFM3 
                 BCL6 
                 POU5F1 
                 CAST 
                 FOXN1 
                 BAG3 
               
               
                 CHST4 
                 RFC5 
                 MAB21L1 
                 NOTCH2 
                 RXFP4 
                 KRBA1 
                 FOXH1 
                 EFNA1 
                 LAT 
                 CAMK2N1 
               
               
                 PNLIPRP2 
                 ARMC6 
                 DRD2 
                 PTGFRN 
                 SLC26A3 
                 NR3C1 
                 TRIML2 
                 KDSR 
                 SLC46A2 
                 PCDH1 
               
               
                 PLA2G1B 
                 PCCB 
                 MAB21L1 
                 REST 
                 CDX1 
                 SS18 
                 TRIML2 
                 TICAM1 
                 PTCRA 
                 ZDHHC9 
               
               
                 CHST4 
                 MMACHC 
                 MAB21L1 
                 TRAF4 
                 ASCL2 
                 SS18 
                 TRIML2 
                 FBXO3 
                 GRAP2 
                 ZDHHC9 
               
               
                 PLA2G1B 
                 ATPAF1 
                 DGKK 
                 NOTCH2 
                 PPP1R14D 
                 NR3C1 
                 ZSCAN10 
                 AIG1 
                 GRAP2 
                 BAG3 
               
               
                 PNLIPRP2 
                 PCCB 
                 PENK 
                 ZFP36L1 
                 SLC26A3 
                 KCTD1 
                 VENTX 
                 PPA2 
                 CCR9 
                 SOX13 
               
               
                 PNLIPRP2 
                 TMEM209 
                 HAND2 
                 SERBP1 
                 PPP1R14D 
                 BCL6 
                 FOXH1 
                 MBNL2 
                 CHRM4 
                 EPS8 
               
               
                 PLA2G1B 
                 BTBD6 
                 TLX2 
                 RCC1 
                 ISX 
                 NR3C1 
                 VENTX 
                 CHMP3 
                 CD3D 
                 EFHD2 
               
               
                 CHST4 
                 CLPB 
                 TLX2 
                 TMEM63A 
                 SLC26A3 
                 RAB12 
                 L1TD1 
                 CAST 
                 UBASH3A 
                 BAG3 
               
               
                 CUZD1 
                 CLPB 
                 TLX2 
                 REST 
                 CDX1 
                 PTPRS 
                 L1TD1 
                 TMEM59 
                 CCR9 
                 MANSC1 
               
               
                 CUZD1 
                 TMEM209 
                 DRD2 
                 ERBB2 
                 ISX 
                 SMARCA1 
                 ZFP42 
                 ELOVL1 
                 APOBEC2 
                 PCDH1 
               
               
                 SLC30A8 
                 CELSR2 
                 INSM2 
                 LRRC1 
                 CDX1 
                 SART1 
                 SLC2A14 
                 AIG1 
                 MEIG1 
                 MANSC1 
               
               
                 CUZD1 
                 ORC3 
                 DRGX 
                 RCC1 
                 PPP1R14D 
                 TANC2 
                 VENTX 
                 ELOVL1 
                 TRAT1 
                 FAM114A1 
               
               
                 SCTR 
                 SOX12 
                 DRGX 
                 RPS6KA1 
                 MEPIA 
                 WWTR1 
                 FOXH1 
                 MFSD6 
                 CD3D 
                 JTB 
               
               
                 FOXL1 
                 BTBD6 
                 DRGX 
                 NEK6 
                 MEPIA 
                 BCL6 
                 HYAL4 
                 MFSD6 
                 ZAP70 
                 EFHD2 
               
               
                 SCTR 
                 BTBD6 
                 SLC18A2 
                 VAMP8 
                 GUCY2C 
                 WWTR1 
                 SLC2A14 
                 KLHDC10 
                 SH2D1A 
                 PLBD2 
               
               
                 GPBAR1 
                 SUV39H2 
                 SLC18A2 
                 NEK6 
                 ASCL2 
                 EVL 
                 ZFP42 
                 PTPRK 
                 SLC46A2 
                 MANSC1 
               
               
                 SCTR 
                 MCUR1 
                 NEUROD4 
                 LRRC1 
                 MEP1A 
                 EVL 
                 ZFP42 
                 MBNL2 
                 SH2D1A 
                 CALU 
               
               
                 SFRP5 
                 CELSR2 
                 SLC18A2 
                 TMEM63A 
                 AIFM3 
                 RAB12 
                 ZSCAN10 
                 PTPRK 
                 CCL25 
                 DSTN 
               
               
                 GPBAR1 
                 MMACHC 
                 TBX20 
                 LRRC1 
                 MYO1A 
                 WWTR1 
                 L1TD1 
                 DAZAP2 
                 SH2D1A 
                 DUSP3 
               
               
                 SFRP5 
                 SOX12 
                 DGKK 
                 TRAF4 
                 GUCY2C 
                 RDX 
                 SLC2A14 
                 ZADH2 
                 CD3G 
                 ADAM9 
               
               
                 FOXL1 
                 PPIL1 
                 INSM2 
                 NEK6 
                 DPEP1 
                 MYH10 
                 HYAL4 
                 ZADH2 
                 UBASH3A 
                 CDC42EP1 
               
               
                 TFF2 
                 PPIL1 
                 PENK 
                 SERBP1 
                 ISX 
                 C20orf194 
                 HYAL4 
                 FBXO3 
                 CD3G 
                 PTK2 
               
               
                 SLC30A8 
                 SOX12 
                 CHGB 
                 B2M 
                 R3HDML 
                 KRBA1 
                 ZSCAN10 
                 ZADH2 
                 CHRM4 
                 SOX13 
               
               
                 SFRP5 
                 ATPAF1 
                 DGKK 
                 TSPAN6 
                 ASCL2 
                 SART1 
                 DPPA2 
                 PTPRK 
                 UBASH3A 
                 FAM114A1 
               
               
                 TFF2 
                 TMEM69 
                 NEUROD4 
                 TSPAN6 
                 DPEP1 
                 ECH1 
                 SLC7A3 
                 NFIC 
                 SIT1 
                 CDC42EP1 
               
               
                 FOXL1 
                 ARMC6 
                 NEUROD4 
                 RCC1 
                 GUCY2C 
                 CDC23 
                 SLC7A3 
                 KLHDC10 
                 APOBEC2 
                 CDC42EP1 
               
               
                 TFF2 
                 PCCB 
                 FAM163A 
                 ANXA11 
                 CDH17 
                 ZFP36 
                 SLC7A3 
                 KDSR 
                 SIT1 
                 B4GALT2 
               
               
                 SLC30A8 
                 TMEM209 
                 HAND1 
                 CDH1 
                 NR1I2 
                 SMARCA1 
                 NODAL 
                 SETD7 
                 ZAP70 
                 PLBD2 
               
               
                 GLP2R 
                 L2HGDH 
                 RTL1 
                 YAP1 
                 PHGR1 
                 PTPRS 
                 NANOS3 
                 EXOC3 
                 CD3G 
                 DUSP3 
               
               
                 REG1B 
                 CSE1L 
                 RTL1 
                 TGIF1 
                 PHGR1 
                 RNF144B 
                 NANOS3 
                 PPA2 
                 CD247 
                 PLBD2 
               
               
                 REG1B 
                 GLO1 
                 PENK 
                 SF3B2 
                 PHGR1 
                 RAB12 
                 NANOS3 
                 CHMP3 
                 ZAP70 
                 JTB 
               
               
                 REG1B 
                 MTCH2 
                 VWA5B2 
                 ANXA11 
                 DPEP1 
                 RDX 
                 CLEC4D 
                 SETD7 
                 SLAMF1 
                 DUSP3 
               
               
                 TM4SF4 
                 ATPAF1 
                 RTL1 
                 LSR 
                 CDH17 
                 DTX3L 
                 NLRP9 
                 SETD7 
                 TRAT1 
                 SLC31A1 
               
               
                 CFC1 
                 GNMT 
                 TBX20 
                 STXBP2 
                 CDH17 
                 ECH1 
                 OOEP 
                 FBXO3 
                 CCL25 
                 ERBB3 
               
               
                 TM4SF4 
                 ARMC6 
                 SLC6A2 
                 LSR 
                 GUCA2A 
                 TMEM25 
                 NLRP9 
                 LRRCC1 
                 CD247 
                 CD276 
               
               
                 TM4SF4 
                 TRUB2 
                 SLC6A2 
                 VAMP8 
                 RXFP4 
                 CLIP4 
                 NLRP9 
                 PPA2 
                 APOBEC2 
                 FAM114A1 
               
               
                 ANXA10 
                 PPIL1 
                 KCNG4 
                 STXBP2 
                 NR1I2 
                 GNB5 
                 RNF17 
                 KDSR 
                 CCL25 
                 EFHD2 
               
               
                 ANXA10 
                 TRUB2 
                 HAND1 
                 REST 
                 GPR35 
                 NAGA 
                 RNF17 
                 PGRMC1 
                 CD3D 
                 YARS 
               
               
                 RBPJL 
                 METTL4 
                 INSM2 
                 TSPAN6 
                 NR1I2 
                 RDX 
                 DPPA2 
                 IL13RA1 
                 SLAMF1 
                 ADAM9 
               
               
                 RBPJL 
                 SNRNP25 
                 SLC6A2 
                 KIF1C 
                 MYO1A 
                 GNB5 
                 RNF17 
                 EXOC3 
                 TRAT1 
                 EPS8 
               
               
                 RBPJL 
                 PCBD2 
                 CHGA 
                 B2M 
                 MYO1A 
                 SMARCA1 
                 CLEC4D 
                 LRRCC1 
                 SLAMF1 
                 SLC31A1 
               
               
                 ANXA10 
                 SNRNP25 
                 FAM163A 
                 KIF1C 
                 EPS8L3 
                 ZFP36 
                 CLEC4D 
                 RPIA 
                 CD8B 
                 CD276 
               
               
                 FFAR1 
                 GNMT 
                 HAND1 
                 STXBP2 
                 GUCA2A 
                 C20orf194 
                 DPPA2 
                 PGRMC1 
                 CD8B 
                 JTB 
               
               
                 FFAR1 
                 KCNAB1 
                 TBX20 
                 CDH1 
                 GUCA2A 
                 B3GALNT1 
                 NODAL 
                 LRRCC1 
                 CD247 
                 PTK2 
               
               
                 FFAR1 
                 PCBD2 
                 KCNG4 
                 CDH1 
                 FAM3D 
                 PTPRS 
                 NODAL 
                 RPIA 
                 SIT1 
                 PRKAR2A 
               
               
                 C1orf127 
                 PCBD2 
                 FAM163A 
                 PLIN3 
                 GPR35 
                 MYH10 
                 OOEP 
                 RPIA 
                 CD8B 
                 PTK2 
               
               
                 C1orf127 
                 GPN3 
                 KCNG4 
                 PHF7 
                 RXFP4 
                 B3GALNT1 
                 OOEP 
                 IL13RA1 
                 LAT 
                 CCDC142 
               
               
                 CFC1 
                 PLCXD2 
                 VWA5B2 
                 DBNL 
                 FAM3D 
                 ZNF532 
                 RPL10L 
                 RHOF 
                 TTC24 
                 CCDC142 
               
               
                 GLP2R 
                 KCNAB1 
                 CARTPT 
                 YAP1 
                 EPS8L3 
                 NAGA 
                 ZNF99 
                 IL13RA1 
                 TTC24 
                 WWC1 
               
               
                 GPBAR1 
                 GPN3 
                 VWA5B2 
                 PTGFRN 
                 FAM3D 
                 GPD2 
                 HOXB1 
                 RHOF 
                 MEIG1 
                 WWC1 
               
               
                 C1orf127 
                 SNRNP25 
                 CARTPT 
                 RPS6KA1 
                 EPS8L3 
                 MYH10 
                 HOXB1 
                 MATN3 
                 LAT 
                 ADAM9 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Gene Pairs For UCEC Sub-Types 
               
            
           
           
               
               
               
               
               
               
            
               
                 Solid Tissue 
                 Solid Tissue 
                   
                   
                   
                   
               
               
                 Normal_1 
                 Normal_2 
                 Endometrioid_1 
                 Endometrioid_2 
                 Serous_1 
                 Serous_2 
               
               
                   
               
               
                 RERG 
                 MKI67 
                 FOXA2 
                 MAGEH1 
                 L1CAM 
                 CDKN1A 
               
               
                 RERG 
                 TMEM132A 
                 KIAA1324 
                 NPR1 
                 L1CAM 
                 MOB3A 
               
               
                 SLC22A3 
                 MYBL2 
                 SPDEF 
                 NPR1 
                 L1CAM 
                 NFIC 
               
               
                 PLSCR4 
                 ZDHHC16 
                 SPDEF 
                 HIF3A 
                 CLDN6 
                 CDKN1A 
               
               
                 PLSCR4 
                 NUP43 
                 FOXA2 
                 HIF3A 
                 CLDN6 
                 MOB3A 
               
               
                 TCF23 
                 MYBL2 
                 FOXA2 
                 PNMA3 
                 CLDN6 
                 NFIC 
               
               
                 MAMDC2 
                 MYBL2 
                 NANS 
                 NPR1 
                 GRB7 
                 CDKN1A 
               
               
                 GATA6 
                 TK1 
                 SPDEF 
                 MAGEH1 
                 GRB7 
                 MOB3A 
               
               
                 PLSCR4 
                 FTSJ1 
                 MYBL2 
                 L1CAM 
                 PNMA3 
                 IL20RA 
               
               
                 RSPO1 
                 MKI67 
                 BSPRY 
                 L1CAM 
                 MYBL2 
                 KIAA1324 
               
               
                 BCHE 
                 MKI67 
                 KIAA1324 
                 HIF3A 
                 SLC6A12 
                 IL20RA 
               
               
                 SLC22A3 
                 CDC20 
                 NANS 
                 ARHGAP23 
                 CDC20 
                 KIAA1324 
               
               
                 RERG 
                 TK1 
                 GALNT10 
                 ARHGAP23 
                 GPRIN2 
                 IL20RA 
               
               
                 GATA6 
                 CDC20 
                 CDC20 
                 L1CAM 
                 UNK 
                 KIAA1324 
               
               
                 RSPO1 
                 CDC20 
                 KIAA1324 
                 FBXO17 
                 GRB7 
                 PGR 
               
               
                 RSPO1 
                 TK1 
                 BSPRY 
                 SLC6A12 
                 PNMA3 
                 PGR 
               
               
                 GATA6 
                 ZDHHC16 
                 OSTF1 
                 FBXO17 
                 SLC6A12 
                 PGR 
               
               
                 MAGEH1 
                 FTSJ1 
                 BSPRY 
                 FAM110B 
                 CTCFL 
                 NIPAL1 
               
               
                 ASPA 
                 EME1 
                 MLPH 
                 ARHGAP23 
                 SLC6A12 
                 PXK 
               
               
                 BCHE 
                 TBC1D7 
                 OSTF1 
                 MAGEH1 
                 TBC1D7 
                 SPDEF 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Gene Pairs For STAD Sub-Types 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Intestinal_1 
                 Intestinal_2 
                 Diffuse_1 
                 Diffuse _2 
               
               
                   
                   
               
               
                   
                 HOOK1 
                 JAM2 
                 ABCA8 
                 SHPRH 
               
               
                   
                 BUB1 
                 OGN 
                 CHRDL1 
                 TNIK 
               
               
                   
                 HOOK1 
                 CHRDL1 
                 OGN 
                 VPS37A 
               
               
                   
                 HOOK1 
                 OGN 
                 NGFR 
                 LYRM4 
               
               
                   
                 FAM136A 
                 GYPC 
                 JAM2 
                 LYRM4 
               
               
                   
                 AURKA 
                 OGN 
                 CHRDL1 
                 TRAFD1 
               
               
                   
                 BUB1 
                 NGFR 
                 JAM2 
                 STIM2 
               
               
                   
                 DSN1 
                 JAM2 
                 JAM2 
                 VPS37A 
               
               
                   
                 BUB1 
                 JAM2 
                 NGFR 
                 SHPRH 
               
               
                   
                 DSN1 
                 SELP 
                 CADM3 
                 ZNF112 
               
               
                   
                 DSN1 
                 ABCA8 
                 SRPX 
                 STIM2 
               
               
                   
                 PIGU 
                 GYPC 
                 ABCA8 
                 LYRM4 
               
               
                   
                 RAE1 
                 BOC 
                 CHRDL1 
                 VPS37A 
               
               
                   
                 AURKA 
                 NGFR 
                 OGN 
                 TRAFD1 
               
               
                   
                 UBE2C 
                 GYPC 
                 PKNOX2 
                 ZNF112 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Gene Pairs For PADD Sub-Types 
               
            
           
           
               
               
               
               
               
               
            
               
                 LowPurity_1 
                 LowPurity_2 
                 basal_1 
                 basal_2 
                 classical_1 
                 classical_2 
               
               
                   
               
               
                 RHOJ 
                 EFNA4 
                 BCAR3 
                 BTG2 
                 LRRC66 
                 LDLRAD3 
               
               
                 JAM2 
                 SAMD10 
                 GPR87 
                 FRZB 
                 IHH 
                 DSE 
               
               
                 PREX1 
                 PTK6 
                 COX6B2 
                 NOSTRIN 
                 LRRC66 
                 TTC7B 
               
               
                 FBLN5 
                 MANBAL 
                 FBXL2 
                 FRZB 
                 ZFPM1 
                 RDX 
               
               
                 CYYR1 
                 EFNA4 
                 COX6B2 
                 FMO5 
                 IHH 
                 CAMK1D 
               
               
                 ERG 
                 EFNA4 
                 BEAN1 
                 NOSTRIN 
                 SPIRE2 
                 CHST11 
               
               
                 FBLN5 
                 ICA1 
                 MET 
                 CAPRIN1 
                 FMO5 
                 PTPRS 
               
               
                 CXCL12 
                 KRTCAP3 
                 GPR87 
                 NOSTRIN 
                 FMO5 
                 MYO5A 
               
               
                 ST8SIA4 
                 SAMD10 
                 RYK 
                 BTG2 
                 TM4SF5 
                 CAMK1D 
               
               
                 BCL2 
                 SAMD10 
                 GPR87 
                 FMO5 
                 C9orf152 
                 CITED2 
               
               
                 SAMHD1 
                 MST1R 
                 COX6B2 
                 BLNK 
                 TM4SF5 
                 PTPRS 
               
               
                 FBLN5 
                 ELMO3 
                 NT5E 
                 BTG2 
                 C9orf152 
                 PTPRS 
               
               
                 SAMHD1 
                 B3GNT3 
                 BCAR3 
                 TMEM98 
                 IHH 
                 MYO5A 
               
               
                 MPP1 
                 SPIRE2 
                 BEAN1 
                 KALRN 
                 TM4SF5 
                 MCC 
               
               
                 JAM2 
                 NXT1 
                 FBXL2 
                 RAI2 
                 C9orf152 
                 PHLDB2 
               
               
                 BCL2 
                 PORCN 
                 FBXL2 
                 PDX1 
                 SPIRE2 
                 FMNL1 
               
               
                 PRCP 
                 OCIAD2 
                 ANXA8 
                 ARHGAP24 
                 AGR3 
                 EVL 
               
               
                 PRCP 
                 SSH3 
                 ANXA8 
                 RAI2 
                 SPIRE2 
                 RDX 
               
               
                 PRCP 
                 B3GNT3 
                 SIX4 
                 CHN2 
                 ZFPM1 
                 FMNL1 
               
               
                 GNG2 
                 NXT1 
                 NT5E 
                 TMEM98 
                 LRRC66 
                 SACS 
               
               
                 GIMAP4 
                 IGSF9 
                 BEAN1 
                 PDX1 
                 ZFPM1 
                 CHST3 
               
               
                 RASSF2 
                 ADAP1 
                 ANXA8 
                 BLNK 
                 ANKS4B 
                 CAMK1D 
               
               
                 ADPRH 
                 C1D 
                 TNNT1 
                 EXOC6 
                 AGR3 
                 RDX 
               
               
                 CELF2 
                 PITX1 
                 ARNTL2 
                 MAPRE2 
                 AGR3 
                 DENND5A 
               
               
                 BCL2 
                 C1D 
                 PORCN 
                 KALRN 
                 FMO5 
                 PHLDB2 
               
               
                 JAM2 
                 IGSF9 
                 BCAR3 
                 MAPRE2 
                 FOXA3 
                 EFEMP1 
               
               
                 SAMHD1 
                 OCIAD2 
                 TNNT1 
                 KALRN 
                 TRIM15 
                 PHLDB2 
               
               
                 CYYR1 
                 IGSF9 
                 PORCN 
                 C1orf115 
                 FOXA3 
                 NDST1 
               
               
                 METTL7A 
                 TSPAN15 
                 ADAMTSL5 
                 FMO5 
                 TRIM15 
                 CHST3 
               
               
                 ST8SIA4 
                 C1D 
                 SIX4 
                 ASRGL1 
                 NPAS1 
                 P2RY6 
               
               
                 GIMAP4 
                 PITX1 
                 PTK6 
                 ATP2A3 
                 ICA1 
                 ELL2 
               
               
                 CD8A 
                 ADAMTSL5 
                 PORCN 
                 ARL15 
                 KALRN 
                 EVL 
               
               
                 CD8A 
                 CENPE 
                 PLXNA1 
                 CTSS 
                 ADAP1 
                 DNAJC13 
               
               
                 CERKL 
                 CENPE 
                 PLXNA1 
                 ATP2A3 
                 CRB3 
                 NIN 
               
               
                 ST8SIA4 
                 PORCN 
                 FSCN1 
                 ATP2A3 
                 ANKS4B 
                 DYSF 
               
               
                 ERG 
                 NXT1 
                 TNNT1 
                 PDX1 
                 ADAP1 
                 EVL 
               
               
                 RASSF2 
                 PTK6 
                 SIX4 
                 ARHGAP24 
                 USH1C 
                 CNN3 
               
               
                 CXCL12 
                 SH3RF1 
                 C16orf74 
                 CEBPA 
                 ADAP1 
                 CHST11 
               
               
                 CXCL12 
                 PREB 
                 MET 
                 CTSS 
                 LRCH1 
                 DENND5A 
               
               
                 PREX1 
                 ICA1 
                 FAM83A 
                 METTL7A 
                 KALRN 
                 NIN 
               
               
                 RHOJ 
                 SPIRE2 
                 ARNTL2 
                 IQGAP2 
                 BDH1 
                 DYSF 
               
               
                 AOAH 
                 ADAMTSL5 
                 PTK6 
                 EPS8L3 
                 USH1C 
                 ETS1 
               
               
                 GAB3 
                 ADAMTSL5 
                 C16orf74 
                 ASRGL1 
                 APOBEC1 
                 P2RY6 
               
               
                 MPP1 
                 PITX1 
                 SNCG 
                 LPAR6 
                 TRIM15 
                 DYSF 
               
               
                 PREX1 
                 ADAP1 
                 SNCG 
                 C1orf115 
                 FOXA3 
                 FMNL1 
               
               
                 CD8A 
                 CHEK2 
                 PTK6 
                 IQGAP2 
                 EPS8L3 
                 ETS1 
               
               
                 EVL 
                 PREB 
                 SNCG 
                 ARL15 
                 SLC45A3 
                 NDST1 
               
               
                 GIMAP6 
                 CENPV 
                 PRRC1 
                 METTL7A 
                 TJP3 
                 ETS1 
               
               
                 GIMAP4 
                 VAMP4 
                 FAM3C 
                 METTL7A 
                 CYP251 
                 CNN3 
               
               
                 GIMAP8 
                 RBFA 
                 ITGA3 
                 R13516 
                 ITPKA 
                 SLC37A2 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Gene Pairs For LUSC Sub-Types 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 primitive_1 
                 primitive_2 
                 secretory_1 
                 secretory_2 
                 basal_1 
                 basal_2 
                 classical_1 
                 classical_2 
               
               
                   
               
               
                 SBK1 
                 MAFB 
                 CIITA 
                 PIR 
                 SERPINB3 
                 TXNRD1 
                 TMEM116 
                 GPSM3 
               
               
                 ATAT1 
                 IL1RN 
                 FMNL1 
                 FBXO45 
                 HES2 
                 MEGF9 
                 MRAP2 
                 ACSL5 
               
               
                 MEX3A 
                 MAFB 
                 TNFRSF1B 
                 SIAH2 
                 IL1RN 
                 TXNRD1 
                 CYP4F3 
                 KRT7 
               
               
                 CSTF1 
                 RIN2 
                 TNFRSF1B 
                 POLR2H 
                 CXCL1 
                 CDK5RAP2 
                 TSPAN7 
                 FAM107B 
               
               
                 SBK1 
                 IL1RN 
                 TNFRSF1B 
                 ZNF639 
                 SERPINB3 
                 EPCAM 
                 TMEM116 
                 ZFAND2B 
               
               
                 SBK1 
                 S100A8 
                 RFTN1 
                 FBXO45 
                 FAM83A 
                 CDK5RAP2 
                 MRAP2 
                 PDZD2 
               
               
                 FAM184A 
                 RAB27B 
                 FMNL1 
                 MRPL47 
                 CXCL1 
                 RIT1 
                 OSGIN1 
                 CXXC5 
               
               
                 FAM184A 
                 CIITA 
                 ABI3BP 
                 ECE2 
                 PTPRH 
                 FANCC 
                 OSGIN1 
                 CRIP2 
               
               
                 HES6 
                 MAFB 
                 ANXA6 
                 ACTL6A 
                 PTK6 
                 MAFG 
                 TMEM116 
                 CXXC5 
               
               
                 HES6 
                 S100A8 
                 FLI1 
                 DENND2C 
                 CXCL1 
                 ME1 
                 ME1 
                 PHC2 
               
               
                 FAM184A 
                 ABI3BP 
                 SELPLG 
                 ECE2 
                 PTK6 
                 CDK5RAP2 
                 ADAM23 
                 PHC2 
               
               
                 TOX3 
                 TMEM116 
                 ANXA6 
                 PCYT1A 
                 FABP5 
                 STARD7 
                 MRAP2 
                 TMEM51 
               
               
                 VIL1 
                 SERPINB3 
                 ANXA6 
                 GMPS 
                 FAM83A 
                 GTF3C4 
                 MAFG 
                 FAM107B 
               
               
                 HES6 
                 GJB3 
                 BIRC3 
                 ZNF639 
                 GPR153 
                 CTNNAL1 
                 CYP4F11 
                 CRIP2 
               
               
                 MEX3A 
                 PHLDA3 
                 ETS1 
                 PCYT1A 
                 GPR153 
                 GTF3C4 
                 TSPAN7 
                 PMEPA1 
               
               
                 SRCIN1 
                 ANXA8 
                 TGM2 
                 PFN2 
                 FAM83A 
                 MAFG 
                 TSPAN7 
                 CRIP2 
               
               
                 MEX3A 
                 TUBB6 
                 ABI3BP 
                 MOB2 
                 FABP5 
                 TXNRD1 
                 SCN9A 
                 CXXC5 
               
               
                 TUBB2B 
                 RAC2 
                 ABI3BP 
                 DENND2C 
                 SERPINB3 
                 ME1 
                 SCN9A 
                 SLC43A3 
               
               
                 VIL1 
                 S100A8 
                 C1orf162 
                 DENND2C 
                 CXCL6 
                 WASF1 
                 SCN9A 
                 GPSM3 
               
               
                 SRCIN1 
                 RAB27B 
                 FLI1 
                 WDR53 
                 S100A8 
                 TALDO1 
                 CYP4F11 
                 PHC2 
               
               
                 VIL1 
                 ANXA8 
                 SLCO2A1 
                 PIR 
                 GJB3 
                 CBX1 
                 CYP4F11 
                 KRT7 
               
               
                 ATAT1 
                 RAB27B 
                 CIITA 
                 MAFG 
                 FABP5 
                 PGD 
                 PIR 
                 TRIM8 
               
               
                 TUBB2B 
                 TNFRSF1B 
                 LTB 
                 GPX2 
                 EPS8L1 
                 CTNNAL1 
                 ME1 
                 PTP4A2 
               
               
                 TOX3 
                 PDZK1IP1 
                 TSPAN4 
                 FBXO45 
                 HES2 
                 GTF3C4 
                 OSGIN1 
                 TMEM51 
               
               
                 ATAT1 
                 GJB3 
                 BIRC3 
                 RIT1 
                 HES2 
                 MAFG 
                 TXN 
                 SDC4 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Gene Pairs For LUAD Sub-Types 
               
            
           
           
               
               
               
               
               
               
            
               
                 prox.-inflam_1 
                 prox.-inflam_2 
                 TRU_1 
                 TRU_2 
                 prox.-prolif._1 
                 prox.-prolif._2 
               
               
                   
               
               
                 CD274 
                 KIAA1324 
                 PLA2G4F 
                 NUF2 
                 CABYR 
                 PER3 
               
               
                 BEND6 
                 GJB1 
                 SCTR 
                 CEP55 
                 FGL1 
                 PER3 
               
               
                 TNFSF4 
                 GJB1 
                 SCTR 
                 KIF2C 
                 C2CD4D 
                 HPGDS 
               
               
                 SPHK1 
                 C9orf152 
                 SCTR 
                 KIF4A 
                 FGL1 
                 TLR2 
               
               
                 RGS10 
                 RAP1GAP 
                 PLA2G4F 
                 NEK2 
                 FGL1 
                 CIITA 
               
               
                 PLAU 
                 MTUS1 
                 PLLP 
                 BIRC5 
                 CABYR 
                 ARHGAP20 
               
               
                 NTAN1 
                 FAM174B 
                 PLA2G4F 
                 PRR11 
                 SLC16A14 
                 CIITA 
               
               
                 PDCD1LG2 
                 GJB1 
                 HLF 
                 KIF11 
                 CABYR 
                 MAML2 
               
               
                 DSE 
                 RAP1GAP 
                 PLLP 
                 CDK1 
                 SLC16A14 
                 MAML2 
               
               
                 CMTM3 
                 RAP1GAP 
                 HLF 
                 CEP55 
                 VAX2 
                 HPGDS 
               
               
                 ANLN 
                 GPT2 
                 SUSD2 
                 KPNA2 
                 FGA 
                 DPYD 
               
               
                 CTHRC1 
                 CIT 
                 INMT 
                 BIRC5 
                 FGA 
                 HLA-DMB 
               
               
                 ANLN 
                 CABLES1 
                 ADAMTS8 
                 CENPA 
                 SLC48A1 
                 TLR2 
               
               
                 CD274 
                 INMT 
                 HLF 
                 BUB1 
                 SLC16A14 
                 ATP10A 
               
               
                 TPX2 
                 GPT2 
                 ADAMTS8 
                 PBK 
                 ABCB6 
                 FAS 
               
               
                 RGS10 
                 FAM174B 
                 ADAMTS8 
                 NUF2 
                 GPT2 
                 EMP1 
               
               
                 DSE 
                 CABLES1 
                 INMT 
                 KIF11 
                 FGA 
                 CIITA 
               
               
                 NTAN1 
                 KIAA1324 
                 TNXB 
                 KIF11 
                 GPT2 
                 HLA-DMB 
               
               
                 DSE 
                 SLC48A1 
                 SCN4B 
                 CKAP2L 
                 PBK 
                 ATP10A 
               
               
                 CD109 
                 TOB1 
                 INMT 
                 CDK1 
                 ENO3 
                 ARHGAP20 
               
               
                 CD109 
                 FAM174B 
                 RTN4RL1 
                 CENPA 
                 S100P 
                 EMP1 
               
               
                 RGS10 
                 SLC48A1 
                 TMPRSS2 
                 KPNA2 
                 PBK 
                 DAPP1 
               
               
                 CD109 
                 KIAA1324 
                 SCN4B 
                 CENPA 
                 ENO3 
                 PER3 
               
               
                 CD274 
                 C9orf152 
                 CBX7 
                 CEP55 
                 PBK 
                 FAS 
               
               
                 ANLN 
                 SORBS2 
                 NFIX 
                 KPNA2 
                 GPT2 
                 SPRED1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Gene Pairs For LGG Sub-Types 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 ME_1 
                 ME_2 
                 PN_1 
                 PN_2 
                 CL_1 
                 CL_2 
                 NE_1 
                 NE_2 
               
               
                   
               
               
                 IL1R1 
                 KLHL23 
                 SLCO5A1 
                 NIPAL2 
                 MEOX2 
                 NALCN 
                 NAPB 
                 LIMA1 
               
               
                 IL1R1 
                 BCL7A 
                 FERMT1 
                 KCNAB2 
                 IGFBP2 
                 ACTR1A 
                 NAPB 
                 MIDN 
               
               
                 IL1R1 
                 DSCAM 
                 DSCAM 
                 SYNPO 
                 MEOX2 
                 REPS2 
                 CAMKK1 
                 NKIRAS2 
               
               
                 TYMP 
                 CRTC1 
                 FAM110B 
                 SYNPO 
                 MEOX2 
                 GNAI1 
                 GDA 
                 NKIRAS2 
               
               
                 TYMP 
                 BCL7A 
                 FERMT1 
                 SYNPO 
                 TLK1 
                 RAB18 
                 MAL2 
                 NUBP1 
               
               
                 TYMP 
                 RUNDC3A 
                 SHD 
                 NAPB 
                 FBXO17 
                 TMEFF2 
                 KCNAB2 
                 MIDN 
               
               
                 CD3D 
                 TBR1 
                 GPR173 
                 UGP2 
                 HS3ST3B1 
                 PCBP3 
                 KCNAB2 
                 LIMA1 
               
               
                 GPR65 
                 ANAPC1 
                 SLCO5A1 
                 OCIAD2 
                 PIPOX 
                 MAGEH1 
                 KCNAB2 
                 CDC42SE1 
               
               
                 RAB27A 
                 MEIS1 
                 BCL7A 
                 UGP2 
                 PIPOX 
                 DNM3 
                 SULT4A1 
                 PPP1R18 
               
               
                 GPR65 
                 PTS 
                 SLCO5A1 
                 RGS14 
                 SHOX2 
                 H2AFY2 
                 SULT4A1 
                 LIMA1 
               
               
                 MYO1G 
                 EDN3 
                 PCGF2 
                 FAM131A 
                 HS3ST3B1 
                 H2AFY2 
                 SV2B 
                 NUP188 
               
               
                 TNFAIP8 
                 EDN3 
                 SHD 
                 KCNAB2 
                 MEIS1 
                 GNAI1 
                 GDA 
                 WDR81 
               
               
                 RAB27A 
                 ANAPC1 
                 SHD 
                 UGP2 
                 MEIS1 
                 ASB13 
                 SULT4A1 
                 NUP188 
               
               
                 GPRC5A 
                 RCOR2 
                 FERMT1 
                 SIPA1L1 
                 SH2D4A 
                 PCBP3 
                 CAMKK1 
                 TRAFD1 
               
               
                 FAM20A 
                 KLHL23 
                 DSCAM 
                 SIPA1L1 
                 OCIAD2 
                 TMEFF2 
                 SV2B 
                 PPP1R18 
               
               
                 CD3D 
                 GABRA1 
                 RCOR2 
                 FAM131A 
                 SHOX2 
                 PCBP3 
                 GABRA1 
                 NKIRAS2 
               
               
                 RAB27A 
                 KLHL23 
                 RCOR2 
                 RALB 
                 PIPOX 
                 ARL3 
                 CACNG3 
                 DDX19B 
               
               
                 KYNU 
                 EDN3 
                 GPR173 
                 HOPX 
                 HS3ST3B1 
                 TMEFF2 
                 SYNPR 
                 BAZ1A 
               
               
                 CD3G 
                 TBR1 
                 GPR173 
                 FAM131A 
                 IGFBP2 
                 WAC 
                 RBFOX1 
                 BAZ1A 
               
               
                 CD96 
                 CACNG3 
                 BCL7A 
                 SIPA1L1 
                 IGFBP2 
                 SAR1A 
                 MAL2 
                 ANAPC1 
               
               
                 PTPN22 
                 CACNG3 
                 JPH4 
                 NAPB 
                 FBXO17 
                 GNAI1 
                 TBR1 
                 DDX19B 
               
               
                 PTPN22 
                 RYR2 
                 H2AFY2 
                 CAMKK1 
                 DMRTA2 
                 AIFM2 
                 NAPB 
                 PTBP1 
               
               
                 CD96 
                 TBR1 
                 DSCAM 
                 HOPX 
                 MCCC1 
                 ARL3 
                 CAMKK1 
                 ARHGAP17 
               
               
                 TNFAIP8 
                 AIFM2 
                 ZNF74 
                 CYB561 
                 MEIS1 
                 GALNT13 
                 PTER 
                 DDX19B 
               
               
                 GPRC5A 
                 CAMKK1 
                 USP49 
                 CYB561 
                 FBXO17 
                 REPS2 
                 PTER 
                 NUBP1 
               
               
                 TREM1 
                 SYNPR 
                 TMEFF2 
                 CAMKK1 
                 DMRTA2 
                 DDX19B 
                 GDA 
                 STK10 
               
               
                 GPRC5A 
                 ZNF74 
                 RCOR2 
                 HOPX 
                 DMRTA2 
                 TTN 
                 SV2B 
                 TRAFD1 
               
               
                 MYO1G 
                 AMY2B 
                 PCGF2 
                 RALB 
                 MCCC1 
                 DNM3 
                 PTER 
                 INTS9 
               
               
                 FAM20A 
                 ZNF74 
                 USP49 
                 CXCL14 
                 ARAP3 
                 DNM3 
                 RYR2 
                 BAZ1A 
               
               
                 FAM20A 
                 DSCAM 
                 ZNF74 
                 LGALS8 
                 SHOX2 
                 TTN 
                 CCK 
                 STK10 
               
               
                 CD3D 
                 RBP4 
                 JPH4 
                 KCNAB2 
                 NPNT 
                 JPH4 
                 CPNE6 
                 MAN2B1 
               
               
                 CD96 
                 MAL2 
                 USP49 
                 DYNLT3 
                 ARAP3 
                 GALNT13 
                 CACNG3 
                 NUBP1 
               
               
                 GPR65 
                 MEIS1 
                 ZNF74 
                 DYNLT3 
                 SHROOM3 
                 REPS2 
                 RBFOX1 
                 STK10 
               
               
                 SNX20 
                 AIFM2 
                 GALNT13 
                 NAPB 
                 OTX1 
                 SH3GL2 
                 CACNG3 
                 ANAPC1 
               
               
                 TREM1 
                 GABRA1 
                 PTS 
                 KLHL26 
                 PDPN 
                 JPH4 
                 CPNE6 
                 WDR81 
               
               
                 TREM1 
                 RYR2 
                 KLHL23 
                 RALB 
                 TNFAIP6 
                 H2AFY2 
                 RBFOX1 
                 MAN2B1 
               
               
                 CD3G 
                 SH2D7 
                 PCGF2 
                 CXCL14 
                 WIPF3 
                 SH3GL2 
                 FAM131A 
                 TRAFD1 
               
               
                 PTPN22 
                 HCN1 
                 AMOTL2 
                 ANKRD11 
                 PDPN 
                 MXI1 
                 SYNPR 
                 ANAPC1 
               
               
                 IL15 
                 PCDH8 
                 H2AFY2 
                 CPNE6 
                 EMP3 
                 KCNAB2 
                 CCK 
                 INTS9 
               
               
                 MYO1G 
                 TMIE 
                 OLIG2 
                 NDST1 
                 ARAP3 
                 ASB13 
                 CCK 
                 MAN2B1 
               
               
                 TNFAIP8 
                 TTN 
                 OLIG2 
                 CLSTN1 
                 EMP3 
                 ASB13 
                 GABRA1 
                 PPP1R18 
               
               
                 MMP19 
                 TTN 
                 TMEFF2 
                 GDA 
                 EMP3 
                 GALNT13 
                 GABRA1 
                 INTS9 
               
               
                 IL15 
                 GABRA1 
                 PTS 
                 DYNLT3 
                 MCCC1 
                 MAGEH1 
                 CPNE6 
                 ARHGAP17 
               
               
                 LCK 
                 PPP1R1C 
                 SOX6 
                 TMEM127 
                 PDPN 
                 WAC 
                 FAM131A 
                 NUP188 
               
               
                 CD3G 
                 CACNG3 
                 PTS 
                 WIPF3 
                 HOPX 
                 ACTR1A 
                 SYNPR 
                 ARHGAP17 
               
               
                 MMP19 
                 SLC25A32 
                 EBF1 
                 OCIAD2 
                 TLK1 
                 MXI1 
                 UGP2 
                 PTBP1 
               
               
                 MMP19 
                 AIFM2 
                 TMEFF2 
                 RBFOX1 
                 TLK1 
                 MICU1 
                 SYNPO 
                 HNRNPAB 
               
               
                 BATF 
                 SYNPR 
                 PATZ1 
                 TMEM127 
                 NPNT 
                 SH3GL2 
                 SLC6A7 
                 TTN 
               
               
                 LY96 
                 MEIS1 
                 H2AFY2 
                 GDA 
                 FABP5 
                 NALCN 
                 CRTC1 
                 MIDN 
               
               
                 BATF 
                 RBP4 
                 FAM110B 
                 TECPR2 
                 WIPF3 
                 KCNAB2 
                 UGP2 
                 HNRNPAB 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Gene Pairs For KIRC Sub-Types 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 Solid Tissue 
                 Solid Tissue 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Normal_1 
                 Normal_2 
                 3_1 
                 3_2 
                 1_1 
                 1_2 
                 2_1 
                 2_2 
                 4_1 
                 4_2 
               
               
                   
               
               
                 PIK3C2G 
                 SIGLEC10 
                 ADAM12 
                 FAAH 
                 ATP11A 
                 PPIA 
                 TAZ 
                 POP4 
                 TIMM8B 
                 ATG2B 
               
               
                 FXYD4 
                 COL23A1 
                 ADAM12 
                 CCDC130 
                 TOLLIP 
                 SLC25A39 
                 TUBGCP6 
                 TSN 
                 MTX1 
                 RAD54L2 
               
               
                 FXYD4 
                 NDUFA4L2 
                 ADAM12 
                 CRB3 
                 ATP11A 
                 OAZ1 
                 TUBGCP6 
                 STRAP 
                 POP4 
                 TAF1 
               
               
                 CLDN8 
                 DDB2 
                 ARL4C 
                 SHMT1 
                 SPATA18 
                 MRPS34 
                 CCDC130 
                 COPS4 
                 TIMM8B 
                 ZFHX3 
               
               
                 CLDN8 
                 SEMA5B 
                 CTHRC1 
                 ACADL 
                 OSBPL1A 
                 SLC25A39 
                 TUBGCP6 
                 MMADHC 
                 MRPS34 
                 UBR5 
               
               
                 CLDN8 
                 STC2 
                 IL2RA 
                 TMEM171 
                 ITGA6 
                 OAZ1 
                 ZNF692 
                 COPS4 
                 POP4 
                 PRDM2 
               
               
                 PIK3C2G 
                 CXXC4 
                 TRAM2 
                 PRKAB1 
                 RAPGEF2 
                 SLC25A39 
                 CCDC84 
                 POP4 
                 MRPS34 
                 HERC1 
               
               
                 PLA2G4F 
                 STC2 
                 PLAUR 
                 ACADL 
                 PRUNE2 
                 OAZ1 
                 CCDC84 
                 PIGC 
                 MRPS34 
                 ARID1B 
               
               
                 GGT6 
                 STC2 
                 ARL4C 
                 IMPA2 
                 SPATA18 
                 PSMB3 
                 TAZ 
                 PIGC 
                 MRPL17 
                 NEK9 
               
               
                 GGT6 
                 HILPDA 
                 SAP30 
                 ACADL 
                 SPATA18 
                 GNG5 
                 ZNF276 
                 COPS4 
                 POP4 
                 ZFHX3 
               
               
                 FAM3B 
                 SPAG4 
                 ADAMTS12 
                 TRPM3 
                 DIP2B 
                 PNKD 
                 ZNF276 
                 PIGC 
                 GRB2 
                 MACF1 
               
               
                 FAM3B 
                 SAP30 
                 ARL4C 
                 ACAA2 
                 BCL2 
                 TMEM219 
                 ZNF276 
                 SPTY2D1 
                 MTX1 
                 NEMF 
               
               
                 FAM3B 
                 TRDMT1 
                 PODNL1 
                 C16orf86 
                 DIP2B 
                 SEC13 
                 CHKB 
                 LSM11 
                 ORAI3 
                 ZFHX3 
               
               
                 SLC26A7 
                 SCARB1 
                 RUNX1 
                 PDZK1 
                 TMCC3 
                 SEC13 
                 CCDC130 
                 POP4 
                 MTX1 
                 ZNF445 
               
               
                 TMPRSS2 
                 SCARB1 
                 ADAMTS12 
                 FAAH 
                 TMCC3 
                 PSMB3 
                 LCAT 
                 GPN3 
                 LSM4 
                 ARID1A 
               
               
                 TMPRSS2 
                 EGLN3 
                 CALU 
                 PEBP1 
                 RIT1 
                 GTF3A 
                 CHKB 
                 KIAA0391 
                 TXNDC17 
                 NR2C2 
               
               
                 FXYD4 
                 BHLHE41 
                 ADAMTS12 
                 PTH2R 
                 TMCC3 
                 GNG5 
                 GPS2 
                 HSF2 
                 CLPP 
                 HERC1 
               
               
                 PIK3C2G 
                 CENPP 
                 BCAT1 
                 ETFDH 
                 ARHGAP42 
                 PNKD 
                 CCDC130 
                 MMGT1 
                 ORAI3 
                 DICER1 
               
               
                 PLA2G4F 
                 SEMA5B 
                 RUNX1 
                 RIT1 
                 LYSMD3 
                 LSM4 
                 TAZ 
                 USP39 
                 PRELID1 
                 ARID1A 
               
               
                 PLA2G4F 
                 COL23A1 
                 RUNX1 
                 TOLLIP 
                 RAVER2 
                 SLC50A1 
                 CCDC84 
                 MMGT1 
                 MRPL51 
                 UBR5 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 Gene Pairs For HNSC Sub-Types 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Solid 
                 Solid 
                   
                   
                   
                   
               
               
                 Tissue 
                 Tissue 
               
               
                 Normal_1 
                 Normal_2 
                 Atypical_1 
                 Atypical_2 
                 Classical_1 
                 Classical_2 
               
               
                   
               
               
                 FAM3D 
                 TGFB1 
                 ME11 
                 VEGFC 
                 ASNS 
                 SAMHD1 
               
               
                 FAM107A 
                 LOXL2 
                 ME11 
                 PDGFC 
                 TMEM116 
                 CCDC69 
               
               
                 CLEC3B 
                 NID2 
                 FOXRED2 
                 PRSS23 
                 SCN9A 
                 APOL3 
               
               
                 EMCN 
                 NID2 
                 ZNF541 
                 VEGFC 
                 OSGIN1 
                 SAMHD1 
               
               
                 GPD1L 
                 ELF4 
                 ZNF541 
                 DACT1 
                 ARTN 
                 MOB3B 
               
               
                 FAM3D 
                 TTYH3 
                 SYCP2 
                 PODNL1 
                 SCN9A 
                 CCDC69 
               
               
                 CLEC3B 
                 ASPN 
                 MEI1 
                 FSTL3 
                 EPCAM 
                 SAMHD1 
               
               
                 SH3BGRL2 
                 TGFB1 
                 FOXRED2 
                 USP10 
                 B4GALNT4 
                 CCDC69 
               
               
                 SH3BGRL2 
                 TTYH3 
                 SYNGR3 
                 FSTL3 
                 GUI 
                 APOL3 
               
               
                 SH3BGRL2 
                 DNAJC13 
                 SYCP2 
                 VEGFC 
                 TMEM116 
                 ARHGEF10L 
               
               
                 CLEC3B 
                 PCDH12 
                 FOXRED2 
                 FBLIM1 
                 SCN9A 
                 UBA7 
               
               
                 FAM107A 
                 ADAMTS2 
                 ZNF541 
                 P4HA3 
                 CYP4F11 
                 IL4R 
               
               
                 FAM3D 
                 TPX2 
                 SYNGR3 
                 FBXO44 
                 TMEM116 
                 UBA7 
               
               
                 GPD1L 
                 MYBL2 
                 SYNGR3 
                 PRR5 
                 PANX2 
                 TMEM51 
               
               
                 NRG2 
                 NOX4 
                 CEP70 
                 PDGFC 
                 ARTN 
                 APOL3 
               
               
                 GPD1L 
                 FOXM1 
                 SYCP2 
                 F2RL1 
                 CYP4F11 
                 RAP1A 
               
               
                 FAM107A 
                 OLFML2B 
                 ILDR1 
                 PDGFC 
                 GLI2 
                 TMEM51 
               
               
                 ATP6V0A4 
                 LOXL2 
                 C19orf57 
                 UBTD1 
                 CYP4F11 
                 PRDM2 
               
               
                 PLIN4 
                 LOXL2 
                 FAM83E 
                 PAQR5 
                 RIT1 
                 RAP1A 
               
               
                 NDRG2 
                 LAMC2 
                 FAM83E 
                 RUSC2 
                 OSGIN1 
                 CASP4 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Mesenchymal_1 
                 Mesenchymal_2 
                 Basal_1 
                 Basal_2 
               
               
                   
                   
               
               
                   
                 ASPN 
                 RAPGEFL1 
                 RGS20 
                 ZDHHC2 
               
               
                   
                 POSTN 
                 CD9 
                 TRPV3 
                 ZDHHC2 
               
               
                   
                 OLFML2B 
                 MAPK13 
                 TRPV3 
                 GPRC5B 
               
               
                   
                 OLFML2B 
                 RAPGEFL1 
                 HTR7 
                 GPRC5B 
               
               
                   
                 TGFB3 
                 ERBB3 
                 TRPV3 
                 PBX1 
               
               
                   
                 ASPN 
                 ERBB3 
                 HTR7 
                 EPS8 
               
               
                   
                 PCOLCE 
                 MAPK13 
                 RGS20 
                 GPRC5B 
               
               
                   
                 ADAMTS2 
                 SLC9A3R1 
                 FLRT3 
                 PTPRS 
               
               
                   
                 PCOLCE 
                 RAPGEFL1 
                 GOLGA7B 
                 NTRK2 
               
               
                   
                 ASPN 
                 ELF3 
                 FLRT3 
                 PBX1 
               
               
                   
                 PCOLCE 
                 RAB25 
                 HTR7 
                 ZDHHC2 
               
               
                   
                 OLFML2B 
                 STAP2 
                 RGS20 
                 EPS8 
               
               
                   
                 DACT1 
                 CAMSAP3 
                 FLRT3 
                 LTBP3 
               
               
                   
                 OLFML3 
                 STAP2 
                 SLC6A11 
                 PBX1 
               
               
                   
                 FAP 
                 LLGL2 
                 SH2D5 
                 EPS8 
               
               
                   
                 GLT8D2 
                 CAMSAP3 
                 CDSN 
                 ARHGAP24 
               
               
                   
                 OLFML3 
                 LLGL2 
                 SLC6A11 
                 NTRK2 
               
               
                   
                 TGFB3 
                 STAP2 
                 MOB3B 
                 NTRK2 
               
               
                   
                 ADAMTS2 
                 MAPK13 
                 TSPAN10 
                 ARHGAP24 
               
               
                   
                 ADAMTS2 
                 CLDN4 
                 SH2D5 
                 TTC28 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 Gene Pairs For ESCA Sub-Types 
               
            
           
           
               
               
               
               
               
            
               
                   
                 AC_1 
                 AC_2 
                 ESCC_1 
                 ESCC_2 
               
               
                   
                   
               
               
                   
                 HNF4A 
                 TFAP2C 
                 TP63 
                 YKT6 
               
               
                   
                 HNF4A 
                 RNF217 
                 TP63 
                 BRD2 
               
               
                   
                 HNF4A 
                 GPR87 
                 TP63 
                 ATG3 
               
               
                   
                 MUC13 
                 BNC1 
                 ZNF385A 
                 YKT6 
               
               
                   
                 MUC13 
                 SOX15 
                 S1PR5 
                 CD68 
               
               
                   
                 MUC13 
                 TP63 
                 EFS 
                 MRPL1 
               
               
                   
                 EPS8L3 
                 LPAR3 
                 S1PR5 
                 PDF 
               
               
                   
                 EPS8L3 
                 S1PR5 
                 S1PR5 
                 ECM2 
               
               
                   
                 EPS8L3 
                 GPR87 
                 SOX15 
                 TIMM8A 
               
               
                   
                 USH1C 
                 LPAR3 
                 EFS 
                 ECM2 
               
               
                   
                 USH1C 
                 MRPL1 
                 DSC3 
                 YKT6 
               
               
                   
                 TSPAN8 
                 MCC 
                 TFAP2C 
                 MCTP2 
               
               
                   
                 TSPAN8 
                 RNF217 
                 PKP1 
                 BRD2 
               
               
                   
                 TSPAN8 
                 EFS 
                 EFS 
                 MRPL23 
               
               
                   
                 LGALS4 
                 CALML3 
                 SOX15 
                 MCTP2 
               
               
                   
                 LGALS4 
                 TP63 
                 SNAI2 
                 TM2D2 
               
               
                   
                 TMC5 
                 SOX15 
                 PARD6G 
                 MRPL1 
               
               
                   
                 GPR35 
                 S1PR5 
                 BNC1 
                 TIMM8A 
               
               
                   
                 PLEKHA6 
                 EFS 
                 SNAI2 
                 MRPL1 
               
               
                   
                 PRR15L 
                 EFS 
                 DSC3 
                 ATG3 
               
               
                   
                 VIL1 
                 LPAR3 
                 LPAR3 
                 CD68 
               
               
                   
                 VIL1 
                 S1PR5 
                 CALML3 
                 MCTP2 
               
               
                   
                 LGALS4 
                 BNC1 
                 CALML3 
                 MRPL23 
               
               
                   
                 TMC5 
                 TFAP2C 
                 CALML3 
                 TM2D2 
               
               
                   
                 TMC5 
                 MCC 
                 PKP1 
                 SEC31A 
               
               
                   
                 HNF1A 
                 PDF 
                 BNC1 
                 MRPL23 
               
               
                   
                 PLEKHA6 
                 MCC 
                 DSC3 
                 BRD2 
               
               
                   
                 PRR15L 
                 SOX15 
                 BNC1 
                 CD68 
               
               
                   
                 SEMA4G 
                 GPR87 
                 FRMD6 
                 ATG3 
               
               
                   
                 USH1C 
                 PARD6G 
                 GPR87 
                 ECM2 
               
               
                   
                 PLEKHA6 
                 TP63 
                 SOX15 
                 IFIT2 
               
               
                   
                 PRR15L 
                 TFAP2C 
                 GPR87 
                 TIMM8A 
               
               
                   
                 VIL1 
                 TIMM8A 
                 RNF217 
                 TM2D2 
               
               
                   
                 ICA1 
                 PARD6G 
                 FSCN1 
                 SEC31A 
               
               
                   
                 HNF1A 
                 CD68 
                 GPR87 
                 PDF 
               
               
                   
                 HNF1A 
                 CYB5D1 
                 LPAR3 
                 PDF 
               
               
                   
                 RHPN2 
                 BNC1 
                 LPAR3 
                 CYB5D1 
               
               
                   
                 GPR35 
                 PARD6G 
                 S100A2 
                 SEC31A 
               
               
                   
                 GPR35 
                 TIMM8A 
                 SNAI2 
                 MRPL18 
               
               
                   
                 HNF1B 
                 TIMM8A 
                 FRMD6 
                 ANGPTL2 
               
               
                   
                 SEMA4G 
                 SNAI2 
                 PKP1 
                 MRPL18 
               
               
                   
                 SLC44A4 
                 RNF217 
                 S100A2 
                 MRPL18 
               
               
                   
                 CGN 
                 FRMD6 
                 PARD6G 
                 IFIT2 
               
               
                   
                 RHPN2 
                 SNAI2 
                 RHPN2 
                 SLC44A4 
               
               
                   
                 ICA1 
                 SNAI2 
                 S100A2 
                 ANGPTL2 
               
               
                   
                 RHPN2 
                 FRMD6 
                 RNF217 
                 IFIT2 
               
               
                   
                 SLC44A4 
                 FRMD6 
                 GPR35 
                 VIL1 
               
               
                   
                 SLC44A4 
                 CALML3 
                 MCC 
                 ANGPTL2 
               
               
                   
                 FOXA3 
                 CHST6 
                 RNF217 
                 SIGLEC1 
               
               
                   
                 CGN 
                 ZNF385A 
                 SEMA4G 
                 SLC44A4 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 Gene Pairs For COAD Sub-Types 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Solid 
                 Solid 
                   
                   
                   
                   
                   
                   
               
               
                 Tissue 
                 Tissue 
               
               
                 Normal_1 
                 Normal_2 
                 CIN_1 
                 CIN_2 
                 MSI/CIMP_1 
                 MSI/CIMP_2 
                 Invasive_1 
                 Invasive_2 
               
               
                   
               
               
                 ABCA8 
                 URB2 
                 TNNC2 
                 CCL5 
                 ADAMTS2 
                 SLC39A5 
                 APOBEC1 
                 FGFR1 
               
               
                 ABCA8 
                 SLCO4A1 
                 GDPD5 
                 TRIM69 
                 ADAM12 
                 SGK2 
                 QPCT 
                 SIRPA 
               
               
                 ABCA8 
                 TRIB3 
                 GDPD5 
                 ICAM1 
                 TREM1 
                 SLC19A3 
                 QPCT 
                 AQP1 
               
               
                 CA7 
                 FTSJ1 
                 TTI1 
                 LHFPL2 
                 ADAMTS2 
                 IHH 
                 IL33 
                 TNS1 
               
               
                 CA7 
                 GTF2IRD1 
                 SLC5A6 
                 LGMN 
                 OLR1 
                 SLC19A3 
                 QPCT 
                 TNS1 
               
               
                 CA7 
                 KRT80 
                 MOCS3 
                 TRIM69 
                 SLC11A1 
                 PPP1R14C 
                 COMMD10 
                 AQP1 
               
               
                 SCARA5 
                 SLC7A5 
                 TGIF2 
                 TRIM69 
                 ADAM12 
                 PPP1R14C 
                 APOBEC1 
                 SIRPA 
               
               
                 SCARA5 
                 FTSJ1 
                 CDK5RAP1 
                 LHFPL2 
                 SLC11A1 
                 PLA2G4F 
                 APOBEC1 
                 CCDC80 
               
               
                 SCARA5 
                 GTF2IRD1 
                 PIGU 
                 LHFPL2 
                 HAPLN3 
                 ABAT 
                 IL33 
                 SIRPA 
               
               
                 CLEC3B 
                 KRT80 
                 TNNC2 
                 TNFAIP8 
                 ITGAX 
                 SGK2 
                 SLC11A2 
                 AEBP1 
               
               
                 CLEC3B 
                 SLCO4A1 
                 GNG4 
                 SGMS2 
                 ICAM1 
                 SLC39A5 
                 SMAGP 
                 AEBP1 
               
               
                 CLEC3B 
                 TEAD4 
                 TNNC2 
                 HPSE 
                 CLEC5A 
                 SLC19A3 
                 PPA2 
                 TIMP2 
               
               
                 SPIB 
                 URB2 
                 SLC5A6 
                 VAPA 
                 NCF2 
                 SGK2 
                 RAB32 
                 AQP1 
               
               
                 SPIB 
                 SLCO4A1 
                 GNG4 
                 ABHD3 
                 OSM 
                 RNLS 
                 CYP39A1 
                 GPR161 
               
               
                 SPIB 
                 TEAD4 
                 SLC35C2 
                 LGMN 
                 SPP1 
                 CXCL14 
                 COMMD10 
                 TNS1 
               
               
                 GLP2R 
                 KRT80 
                 SLC13A3 
                 FCGR3A 
                 TREM1 
                 RNLS 
                 IL33 
                 EHD2 
               
               
                 GLP2R 
                 CLDN1 
                 GDPD5 
                 TRIB2 
                 SLC11A1 
                 PRRG2 
                 HSD17B4 
                 VIM 
               
               
                 GLP2R 
                 ETV4 
                 GNG4 
                 CD163 
                 C5AR1 
                 PPP1R14C 
                 SLC11A2 
                 IGFBP5 
               
               
                 TMIGD1 
                 URB2 
                 FITM2 
                 ABHD3 
                 SPHK1 
                 PRRG2 
                 SLC11A2 
                 TIMP2 
               
               
                 TMIGD1 
                 TEAD4 
                 SLC13A3 
                 TAGAP 
                 ITGAX 
                 ABAT 
                 HCN1 
                 CCDC8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12 
               
               
                   
               
             
            
               
                 Gene Pairs For BRCA Sub-Types 
               
            
           
           
               
               
               
               
               
               
            
               
                 Solid Tissue 
                 Solid Tissue 
                   
                   
                   
                   
               
               
                 Normal_1 
                 Normal_2 
                 LumA_1 
                 LumA_2 
                 Basal_1 
                 Basal_2 
               
               
                   
               
               
                 CD300LG 
                 MMP11 
                 DEGS2 
                 PHGDH 
                 FOXC1 
                 AR 
               
               
                 TMEM132C 
                 COL10A1 
                 AGR3 
                 AIF1L 
                 NEK2 
                 FOXA1 
               
               
                 CA4 
                 COL10A1 
                 TMC4 
                 PHGDH 
                 FAM171A1 
                 AR 
               
               
                 ABCA10 
                 MMP11 
                 DEGS2 
                 AIF1L 
                 BCL11A 
                 AGR2 
               
               
                 ARHGAP20 
                 MMP11 
                 AGR3 
                 PHGDH 
                 NUSAP1 
                 MLPH 
               
               
                 FXYD1 
                 COL10A1 
                 ZMYND10 
                 PSAT1 
                 CDK1 
                 FOXA1 
               
               
                 PAMR1 
                 SLC35A2 
                 FGD3 
                 IFRD1 
                 ZWINT 
                 MLPH 
               
               
                 CD300LG 
                 PAFAH1B3 
                 MAPT 
                 AIF1L 
                 FOXC1 
                 MAGI1 
               
               
                 TSLP 
                 NEK2 
                 AGR3 
                 ID4 
                 CDK1 
                 MLPH 
               
               
                 PAMR1 
                 PSENEN 
                 DEGS2 
                 MCCC1 
                 NUSAP1 
                 FOXA1 
               
               
                 PAMR1 
                 PYCR1 
                 ABAT 
                 LPIN1 
                 FOXC1 
                 EZH1 
               
               
                 CD300LG 
                 TK1 
                 THSD4 
                 EGFR 
                 CDCA7 
                 AR 
               
               
                 SCARA5 
                 CENPF 
                 ZMYND10 
                 CENPW 
                 KCNK5 
                 AGR2 
               
               
                 BTNL9 
                 SLC50A1 
                 ZMYND10 
                 CENPN 
                 NEK2 
                 AGR2 
               
               
                 MAMDC2 
                 SLC50A1 
                 FGD3 
                 TTLL4 
                 CENPW 
                 SIDT1 
               
               
                 ARHGAP20 
                 TPX2 
                 FGD3 
                 LBR 
                 BCL11A 
                 SPDEF 
               
               
                 MAMDC2 
                 PYCR1 
                 ESR1 
                 CX3CL1 
                 ORC1 
                 SIDT1 
               
               
                 ARHGAP20 
                 ZWINT 
                 ABAT 
                 MCCC1 
                 BCL11A 
                 VIPR1 
               
               
                 MAMDC2 
                 SLC35A2 
                 ESR1 
                 EGFR 
                 NEK2 
                 SPDEF 
               
               
                 SCARA5 
                 SLC50A1 
                 GATA3 
                 YBX1 
                 CENPA 
                 SIDT1 
               
               
                 LYVE1 
                 TK1 
                 NAT1 
                 LBR 
                 KCNK5 
                 FBP1 
               
               
                 SCARA5 
                 TIMELESS 
                 SUSD3 
                 MCCC1 
                 KCNK5 
                 THSD4 
               
               
                 FXYD1 
                 NEK2 
                 KCNJ11 
                 PSAT1 
                 CDCA7 
                 SPDEF 
               
               
                 CA4 
                 NEK2 
                 ABAT 
                 IFRD1 
                 SKP2 
                 CMBL 
               
               
                 LYVE1 
                 MKI67 
                 KCNJ11 
                 DSCC1 
                 SRSF12 
                 DNALI1 
               
               
                 LYVE1 
                 LMNB1 
                 ESR1 
                 ANO6 
                 MTHFD1L 
                 CMBL 
               
               
                 CLEC3B 
                 PAFAH1B3 
                 FOXA1 
                 PGRMC1 
                 CDCA7 
                 FBP1 
               
               
                 BTNL9 
                 SLC35A2 
                 MAPT 
                 EGFR 
                 SFT2D2 
                 REEP5 
               
               
                 CLEC3B 
                 TK1 
                 MLPH 
                 HNRNPD 
                 MTHFD1L 
                 FBP1 
               
               
                 CA4 
                 ASF1B 
                 CA12 
                 CX3CL1 
                 PSAT1 
                 CMBL 
               
               
                 TSLP 
                 CCNE2 
                 EVL 
                 KARS 
                 CENPF 
                 GATA3 
               
               
                 BTNL9 
                 PAFAH1B3 
                 NAT1 
                 SKP2 
                 TPX2 
                 GATA3 
               
               
                 TSLP 
                 CENPK 
                 KCNJ11 
                 PIR 
                 CHODL 
                 DNALI1 
               
               
                 C1QTNF9 
                 CDC25C 
                 SUSD3 
                 RGMA 
                 SFT2D2 
                 RHOB 
               
               
                 ABCA10 
                 TPX2 
                 SLC44A4 
                 KCMF1 
                 TPX2 
                 TBC1D9 
               
               
                 ABCA10 
                 ZWINT 
                 NAT1 
                 IFRD1 
                 PPP1R14C 
                 THSD4 
               
               
                 ASPA 
                 ASF1B 
                 SLC44A4 
                 LPIN1 
                 VGLL1 
                 DNALI1 
               
               
                 C1QTNF9 
                 TAS1R3 
                 SUSD3 
                 TTLL4 
                 VGLL1 
                 VIPR1 
               
               
                 ASPA 
                 DTL 
                 GATA3 
                 HNRNPD 
                 KRT16 
                 THSD4 
               
               
                 GLYAT 
                 ASF1B 
                 TMC4 
                 KCMF1 
                 LMNB1 
                 TBC1D9 
               
               
                 ASPA 
                 CDK1 
                 CA12 
                 YBX1 
                 FAM171A1 
                 EZH1 
               
               
                 CLEC3B 
                 PYCR1 
                 EVL 
                 HNRNPD 
                 MKI67 
                 GATA3 
               
               
                 C1QTNF9 
                 CENPA 
                 MAPT 
                 LPIN1 
                 PPP1R14C 
                 VIPR1 
               
               
                 ACVR1C 
                 TPX2 
                 MLPH 
                 CX3CL1 
                 NUSAP1 
                 TBC1D9 
               
               
                 GLYAT 
                 DTL 
                 SLC44A4 
                 TOMM22 
                 EN1 
                 TMEM86A 
               
               
                 ACVR1C 
                 CENPF 
                 MLPH 
                 ORMDL3 
                 KARS 
                 REEP5 
               
               
                 TMEM132C 
                 CDK1 
                 GATA3 
                 ARL6IP1 
                 TPX2 
                 CA12 
               
               
                 ITM2A 
                 UBE2E1 
                 DNALI1 
                 RGMA 
                 EN1 
                 CROT 
               
               
                 GLYAT 
                 CDK1 
                 FOXA1 
                 TRIM29 
                 UGT8 
                 CROT 
               
               
                 TMEM132C 
                 ZWINT 
                 FOXA1 
                 STAU1 
                 CDK1 
                 CA12 
               
               
                   
               
               
                 LumB_1 
                 LumB_2 
                 Normal_1 
                 Normal_2 
                 Her2_1 
                 Her2_2 
               
               
                   
               
               
                 MCM10 
                 SFRP1 
                 CFI 
                 HLTF 
                 MPHOSPH6 
                 ASB13 
               
               
                 CENPA 
                 FOXC1 
                 LZTS1 
                 HLTF 
                 GRB7 
                 IGF1R 
               
               
                 ESPL1 
                 SFRP1 
                 COL17A1 
                 PEX19 
                 SIDT1 
                 IGF1R 
               
               
                 ESPL1 
                 CX3CL1 
                 SERPINF2 
                 LYSMD1 
                 MPHOSPH6 
                 SCARB1 
               
               
                 DSCC1 
                 SFRP1 
                 COL17A1 
                 OTUD7B 
                 MPHOSPH6 
                 SMAD4 
               
               
                 CCNE2 
                 EGFR 
                 LZTS1 
                 PIGM 
                 PGAP3 
                 IGF1R 
               
               
                 CDC25C 
                 TRIM29 
                 IL3RA 
                 ERI2 
                 PNMT 
                 ZNF516 
               
               
                 CENPK 
                 ID4 
                 CX3CL1 
                 ZNF664 
                 KMO 
                 ASB13 
               
               
                 ESPL1 
                 SLC25A37 
                 ITM2A 
                 COG2 
                 PNMT 
                 GREB1 
               
               
                 CCNE2 
                 TRIM29 
                 PPM1F 
                 OTUD7B 
                 KMO 
                 BCL2 
               
               
                 MCM10 
                 CRYAB 
                 ITM2A 
                 STRBP 
                 PNMT 
                 C1orf226 
               
               
                 EME1 
                 TRIM29 
                 CFI 
                 COG2 
                 MFSD2A 
                 RARG 
               
               
                 DSCC1 
                 FAM171A1 
                 CX3CL1 
                 SDHC 
                 TMEM86A 
                 ASB13 
               
               
                 CDC25C 
                 RGMA 
                 NGFR 
                 COG2 
                 FA2H 
                 C1orf226 
               
               
                 MCM10 
                 FAM171A1 
                 CX3CL1 
                 PEX19 
                 TCAP 
                 NUDT6 
               
               
                 ORC1 
                 FOXC1 
                 ITM2A 
                 KLHL12 
                 SPINK8 
                 RERG 
               
               
                 WDR76 
                 EGFR 
                 PPM1F 
                 HLTF 
                 KMO 
                 EZH1 
               
               
                 CENPN 
                 FAM171A1 
                 NGFR 
                 EZH1 
                 TMEM86A 
                 SCARB1 
               
               
                 CENPA 
                 ID4 
                 CFI 
                 OTUD7B 
                 MFSD2A 
                 SCARB1 
               
               
                 NEK2 
                 SLC25A37 
                 PPM1F 
                 KLHL12 
                 SPINK8 
                 ZNF516 
               
               
                 DSCC1 
                 CRYAB 
                 LZTS1 
                 RBBP5 
                 TMEM86A 
                 BCL2 
               
               
                 CDC25C 
                 ID4 
                 COL17A1 
                 STRBP 
                 ZP2 
                 EDN3 
               
               
                 CCNE2 
                 CRYAB 
                 PTN 
                 RBBP5 
                 FGFR4 
                 STC2 
               
               
                 CENPA 
                 RGMA 
                 NGFR 
                 MAGI1 
                 GRB7 
                 STC2 
               
               
                 NEK2 
                 GSTP1 
                 PTN 
                 PEX19 
                 SPINK8 
                 GREB1 
               
               
                 CDK1 
                 GSTP1 
                 PAMR1 
                 LYSMD1 
                 MFSD2A 
                 RERG 
               
               
                 TPX2 
                 GSTP1 
                 RHOJ 
                 WDR19 
                 NUDT8 
                 C1orf226 
               
               
                 CDC25A 
                 FOXC1 
                 MAMDC2 
                 LYSMD1 
                 FA2H 
                 ZNF516 
               
               
                 ORC1 
                 RGMA 
                 RHOJ 
                 ERI2 
                 FA2H 
                 RERG 
               
               
                 WDR76 
                 SLC25A37 
                 PTN 
                 PIGM 
                 GRB7 
                 SMAD4 
               
               
                 PRIM1 
                 EGFR 
                 EGFR 
                 GNPAT 
                 SIDT1 
                 BCL2 
               
               
                 WDR76 
                 TINAGL1 
                 IL3RA 
                 TADA1 
                 ZP2 
                 NUDT6 
               
               
                 NEK2 
                 CX3CL1 
                 RHOJ 
                 PIGM 
                 SOX11 
                 RARG 
               
               
                 RACGAP1 
                 PNRC1 
                 PAMR1 
                 TADA1 
                 ZP2 
                 MRGPRX3 
               
               
                 DTL 
                 PNRC1 
                 CHST3 
                 RBBP5 
                 FGFR4 
                 RARG 
               
               
                 CENPK 
                 ANXA3 
                 PAMR1 
                 MBOAT1 
                 B4GALNT2 
                 MBOAT1 
               
               
                 CENPN 
                 TCF7L1 
                 PDGFA 
                 PCCB 
                 FGFR4 
                 EZH1 
               
               
                 FANCI 
                 PNRC1 
                 TINAGL1 
                 STRBP 
                 TCAP 
                 KIAA0391 
               
               
                 CENPN 
                 CHST3 
                 TRIM29 
                 GNPAT 
                 DEGS2 
                 ESR1 
               
               
                 DTL 
                 CX3CL1 
                 SERPINF2 
                 MBOAT1 
                 SOX11 
                 SMAD4 
               
               
                 EME1 
                 ANXA3 
                 TRIM29 
                 RRM1 
                 TCAP 
                 GREB1 
               
               
                 PRIM1 
                 TINAGL1 
                 PGC 
                 IARS2 
                 NUDT8 
                 STC2 
               
               
                 PRIM1 
                 TCF7L1 
                 PGC 
                 PGRMC1 
                 CCNE2 
                 MBOAT1 
               
               
                 BRCA1 
                 TINAGL1 
                 PGC 
                 HNRNPD 
                 PSMD3 
                 RPS19 
               
               
                 ORC1 
                 ANXA3 
                 CADM3 
                 EPS15 
                 ABCC2 
                 NUDT6 
               
               
                 DSN1 
                 PPM1F 
                 EDN3 
                 NUDT6 
                 NUDT8 
                 EZH1 
               
               
                 CDC25A 
                 TCF7L1 
                 TINAGL1 
                 KLHL12 
                 SLC44A4 
                 ESR1 
               
               
                 BRCA1 
                 PDZRN3 
                 PNRC1 
                 SDHC 
                 TAS1R3 
                 PMAIP1 
               
               
                 TMEM106C 
                 ZFP36L2 
                 PDGFA 
                 RRM1 
                 CDK1 
                 ESR1 
               
               
                 CENPK 
                 BOC 
                 EGFR 
                 RRM1 
                 ORC1 
                 PMAIP1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13 
               
               
                   
               
               
                 Parameters Used to Train CCN (CCN Subclass Classifiers) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 final 
                 CCN cross 
                 CCN cross 
                   
                   
                   
                   
               
               
                   
                 general 
                 species 
                 technology 
               
               
                 Parameters 
                 CCN 
                 validation 
                 validation 
                 BRCA 
                 COAD 
                 ESCA 
                 HNSC 
               
               
                   
               
               
                 nTopGenes 
                 25 
                 25 
                 25 
                 20 
                 20 
                 20 
                 20 
               
               
                 nTopGenePairs 
                 70 
                 70 
                 70 
                 50 
                 20 
                 50 
                 20 
               
               
                 nRand 
                 70 
                 38 
                 70 
                 20 
                 20 
                 20 
                 15 
               
               
                 nTrees 
                 2000  
                 2000  
                 2000  
                 2000  
                 2000  
                 1000  
                 2000  
               
               
                 stratify 
                 TRUE 
                 TRUE 
                 TRUE 
                 TRUE 
                 TRUE 
                 TRUE 
                 TRUE 
               
               
                 sampsize 
                 60 
                 25 
                 60 
                 20 
                 24 
                 70 
                 40 
               
               
                 weightedDown_total 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
               
               
                 weightedDown_dThresh 
                    0.25 
                    0.25 
                    0.25 
                    0.25 
                    0.25 
                    0.25 
                    0.25 
               
               
                 transprop_xFact 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
               
               
                 weight_broadClass 
                 NA 
                 NA 
                 NA 
                  1 
                  1 
                  5 
                  5 
               
               
                 quickPairs 
                 TRUE 
                 TRUE 
                 TRUE 
                 FALSE 
                 FALSE 
                 FALSE 
                 FALSE 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Parameters 
                 KIRC 
                 LGG 
                 UCEC 
                 PAAD 
                 STAD 
                 LUAD 
                 LUSC 
               
               
                   
               
               
                 nTopGenes 
                 20 
                 20 
                 10 
                 30 
                 20 
                 20 
                 20 
               
               
                 nTopGenePairs 
                 20 
                 50 
                 20 
                 50 
                 15 
                 25 
                 25 
               
               
                 nRand 
                 15 
                 15 
                 15 
                 20 
                 55 
                 600  
                 600  
               
               
                 nTrees 
                 2000  
                 2000  
                 1000  
                 2000  
                 1000  
                 2000  
                 2000  
               
               
                 stratify 
                 TRUE 
                 TRUE 
                 TRUE 
                 TRUE 
                 TRUE 
                 TRUE 
                 TRUE 
               
               
                 sampsize 
                 70 
                 30 
                 15 
                 30 
                 55 
                 60 
                 27 
               
               
                 weightedDown_total 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
                 5.00E+05 
               
               
                 weightedDown_dThresh 
                    0.25 
                    0.25 
                    0.25 
                    0.25 
                    0.25 
                    0.25 
                    0.25 
               
               
                 transprop_xFact 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
                 1.00E+05 
               
               
                 weight_broadClass 
                  1 
                 15 
                 10 
                  5 
                 10 
                  5 
                  5 
               
               
                 quickPairs 
                 FALSE 
                 FALSE 
                 FALSE 
                 FALSE 
                 FALSE 
                 FALSE 
                 FALSE 
               
               
                   
               
            
           
         
       
     
     While the foregoing disclosure has been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be clear to one of ordinary skill in the art from a reading of this disclosure that various changes in form and detail can be made without departing from the true scope of the disclosure and may be practiced within the scope of the appended claims. For example, all the methods, cranial implant devices, and/or component parts or other aspects thereof can be used in various combinations. All patents, patent applications, websites, other publications or documents, and the like cited herein are incorporated by reference in their entirety for all purposes to the same extent as if each individual item were specifically and individually indicated to be so incorporated by reference.