Patent Document

CROSS-REFERENCES 
       [0001]    This application claims the benefit of priority of U.S. Provisional Application Ser. No. 61/040,065, filed on Mar. 27, 2008, the disclosure of which is hereby incorporated by referenced in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to assessment and identification of expression of genes related to vascular-related diseases. The present invention also includes methods of comparing gene expression patterns with respect to various disease states. 
       BACKGROUND OF THE INVENTION 
       [0003]    Pulmonary arterial hypertension (PAH) is an occlusive disease of the pulmonary arteries leading to serious hemodynamic abnormality, right heart failure, and premature death. The molecular mechanisms behind PAH are still unclear. Without a more complete understanding of PAH and how its complex vascular dysfunctions relate to one another, patients will suffer from imprecise diagnosis and drug therapy that may be less than optimal. Despite recent advances and introduction of new clinically approved drugs, the 5-year survival from pulmonary hypertension remains an estimated 50% (Archer and Rich, 2000). Consequently, treatment for PAH, while recently improved, still offers significant and long-lasting improvement in only a minority of patients. A methodology to elucidate the molecular pathways associated with PAH could guide the development of new therapies for this disease. 
         [0004]    Though platelets and other cells may have a role in PAH, pulmonary endothelial cells and pulmonary smooth muscle cells appear to be the primary sites of disease progression (Humbert et al 2004). Molecular pathways that show abnormality in pulmonary endothelial cells and pulmonary smooth muscle cells during PAH include endothelin-1 (Giaid et al 1993), serotonin &amp; serotonin transporter (Marcos et al 2003), thromboxane (Walmrath et al 1997), nitric oxide synthase (Kobs and Chesler 2006), prostacyclins (Gailes, et al 2001), potassium channels (Mandegar et al 2002), BMP signaling (Eddahibi et al 2002), and survivin (McMurtry et al 2005). PAH impairs normal signaling and growth in both pulmonary endothelial and pulmonary smooth muscle cells, yet the cellular abnormalities seem to shift over time in unpredictable patterns that has thus far escaped concise definition (Michelakis, 2006). 
         [0005]    PAH may be understood as proceeding in phases. In early PAH, endothelial apoptosis occurs, probably resulting in pulmonary arteriole plugging and an increase in pulmonary vascular pressure (Michelakis, 2006). In late PAH, chronic exposure to elevated pulmonary artery pressure together with dysfunctional endothelial signaling initiates hyperproliferation of smooth muscle cells (McMurtry et al 2005). Increased concentric pulmonary smooth muscle cell proliferation leads to ever increasing pulmonary artery pressure, right ventricular failure, and death. 
         [0006]    Lung pathology in all PAH patients show thickening throughout the arterial wall of the pulmonary vascular bed. In some forms of the disease, the pulmonary vascular lesions are reversible (e.g. in newborns with congenital heart defects). In other patients, such as those with the idiopathic form, the lesions are irreversible. It is unknown how these variations in PAH relate to one another on a molecular basis (Pearl et al 2002). 
         [0007]    Current therapies for PAH patients primarily target vascular tone. Treatments that aim at correcting potassium channel dysfunction (Machado et al 2001), nitric oxide impairment (Humbert et al 2004), prostacyclin impairment (Tuder et al 1999, Christman et al 1992), and endothelin-1 expression (Giaid et al 1993) have all been clinically available for several years. These therapies offer some relief from hemodynamic symptoms, but most patients show only a transient response. The proliferative disease continues to progress in most PAH patients, resulting in a five year mortality rate that remains at around 50% (Newman et al 2004). 
         [0008]    Currently, there are no clinically available routine means to obtain endothelial and smooth muscle samples from the pulmonary arteries of pulmonary hypertension patients for diagnosis, disease staging or drug discovery. Applicant&#39;s earlier invention, described in U.S. Pat. No. 5,406,959, describes an endoarterial biopsy catheter that has demonstrated its safety and effectiveness in normal canines (Rothman, Mann et al., 1996), canines with experimentally-induced pulmonary hypertension (Rothman, Mann et al., 1998), and canines with single-sided lung transplant rejection (Rothman, Mann et al., 2003). Preliminary studies have also demonstrated the safety and efficacy of a catheter-based method to obtain endovascular samples from a porcine model of PAH. 
         [0009]    Percutaneously-obtained pulmonary endoarterial biopsy samples were found to be of sufficient quantity and quality for porcine whole genome mRNA microarray analysis and microRNA analysis. Whole genome microarray analysis revealed time-sensitive variations in gene expression values as PAH progressed in the subject animal model. Genes previously shown to be associated with PAH displayed changes characteristic of the disease, and genes previously unassociated with PAH also displayed expression level dysregulation. These findings raise the possibility that the endoarterial biopsy catheter combined with microarray analysis may provide a valuable platform for the discovery of novel drug and biomarker targets in pulmonary hypertension and a platform to deliver individualized pharmacotranscriptomics. 
         [0010]    MicroRNA analysis revealed pressure sensitive changes in microRNA expression. As our surgical shunt model of pulmonary hypertension progressed from a high flow low pressure (HFLP) manifestation to a high flow high pressure (HFHP) manifestation, different microRNAs became dysregulated either increasing or decreasing in expression relative to our baseline normal values. 
         [0011]    Most new therapies promise to focus on arresting either the endothelial apoptosis that characterizes early PAH (angiopoetin-1 &amp; endothelial nitric oxide synthase cell-base gene transfer (Zhao et al 2003; 2005), caspase inhibitors (Taraseviciene-Stewart et al 2001)) or the smooth muscle cell proliferation typical of late PAH (dichloroacetate (McMurtry et al 2004), simvastatin (Nishimura et al 2003), sidenafil (Wharton et al 2005), imatinib (Schermuly et al 2005), anti-survivin (McMurtry et al 2005), K+ channel replacement gene therapy (Pozeg et al 2003)). 
         [0012]    Before administering therapies, however, it would be extremely valuable to determine which genes are dysregulated in each PAH patient at any stage of their individual disease progression. Without knowing what genes are aberrant during any point in the patient&#39;s disease course, targeted therapies may miss the mark in some patients. Life threatening side effects may emerge if the wrong cells, at the wrong time, are encouraged to die or proliferate in patients with compromised pulmonary vascular health. 
         [0013]    A powerful method for determining the gene expression levels of thousands of genes simultaneously are DNA microarrays. Initially used for the classification of cancers that were difficult to discriminate histologically (Golub et al 1999, Bhattacharjee et al 2001, and Ramaswamy et al 2001), microarrays have been more recently applied to PAH (Geraci et al 2001). PAH microarray studies have been performed on whole lung homogenates in humans (Fantozzi et al 2005) and rats (Hoshikawa et al 2003), surgically-dissected pulmonary arteries in pigs (Medhora et al 2002), laser-microdissected pulmonary arteries in rats (Kwapiszewska et al 2005), and mononuclear peripheral blood in humans (Bull et al 2004). These studies have been performed to discover potentially novel PAH disease pathways, biomarkers, therapeutic targets and patient classification gene expression profiles. 
         [0014]    To advance PAH microarray studies into practical clinical use, tissue procurement methodologies are required that do not require surgical explant or postmortem procurement, and peripheral blood has thus far proven to be inadequate to discriminate gene expression signatures between subgroups of PAH patients (Bull et al 2004; Bull et al 2007). To take advantage of the full power of microarray technologies in PAH patients, a safe and effective minimally invasive means for the repeat procurement of endovascular samples from living PAH patients is required. 
         [0015]    The present invention provides for the use of a novel interventional catheter, an endoarterial biopsy catheter, to obtain serial biopsy specimens from hypertensive pulmonary vessels for analysis. The ability to procure endothelial and smooth muscle samples in a minimally invasive manner will allow physicians to use microarray profiling and other techniques to classify patients upon initial presentation according to their gene expression signatures, prescribe therapies that target genes empirically found to be dysregulated in each individual patient, and monitor and adjust PAH patient therapy according to subsequent biopsy findings. A greater understanding of the complex molecular pathways underlying each patient&#39;s PAH should enable more precise diagnosis and the delivery of more effective therapies. Also of importance is the ability to discover new uses for existing drugs as well as discovering new drug targets. 
         [0016]    Individualized pharmacotranscriptomics based on endoarterial biopsy and microarray analysis represents a reasonable choice for researchers struggling with the complexities and contradictions of PAH and other vascular diseases. The huge literature generated from in vitro and animal studies falls short, at times, in addressing the actual facts of patient health. Many commentators describe this dilemma as the “bench-to-bedside gap”, where in vitro and animal laboratory data fails to model human disease circumstances (Aird, 2004). Bridging that gap through catheter-based access to the vasculature in a model that recapitulates the clinical and histopathological manifestations of a form of human pulmonary hypertension will likely enable closer correlations between animal studies and patient care, and serve as a model for other vascular-based diseases such as atherosclerosis, congestive heart failure, sickle cell disease, organ transplant rejection, connective tissue diseases, chronic obstructive pulmonary disease, pulmonary embolism, asthma, systemic inflammatory response, battlefield trauma, cancer, sepsis and acute respiratory distress syndrome. There is a need in the art to provide data from gene expression analyses in order to target novel candidates for use in treating or preventing PAH. 
       SUMMARY OF THE INVENTION 
       [0017]    One aspect of the present invention provides for methods of treating an individual suffering from a vascular-related disease comprising the steps of: 
         [0018]    a) obtaining a biopsy sample from the individual&#39;s pulmonary artery; 
         [0019]    b) analyzing gene expression levels of the biopsy sample from the pulmonary artery of the individual and a non-diseased control; 
         [0020]    c) comparing the gene expression levels between the biopsy sample from the pulmonary artery of the individual and the non-diseased control; 
         [0021]    d) identifying at least one gene from step c) that is upregulated or downregulated in the biopsy sample based on the non-diseased control; 
         [0022]    e) obtaining gene products from the genes identified in step c); and 
         [0023]    f) selecting pharmaceutical agents which are known inhibitors of the gene products from the at least one upregulated gene or known promoters of the gene products from the at least one downregulated gene. An additional aspect to the present invention provides for the pharmaceutical agents selected for administration to the individual suffering from the vascular-related disease. In yet another aspect, the individual is categorized based on progression of the vascular-related disease, with the treatment being based on the timing of the disease. 
         [0024]    Another aspect of the present invention provides for a means of comparing varying levels of gene expression based on an animal model for pulmonary arterial hypertension. In a preferred embodiment, the genes expressed in the animal model are genes found to be either upregulated or downregulated. In a more preferred embodiment, the upregulated or downregulated genes are time-dependent based on the time after exposure to the PAH. 
         [0025]    Another aspect of the present invention provides for methods of identifying genes involved in the pathway of PAH based on differential gene expression studies in a time-dependent animal model for PAH. In one embodiment, the genes are compared to other known genes which are upregulated or downregulated in the known PAH pathway. 
         [0026]    Yet another aspect of the present invention provides for methods of diagnosing a vascular-related disease in an individual comprising the steps of:
       a) identifying at least one gene that is upregulated or downregulated in the vascular-related disease comprising the steps of:
           1) obtaining a biopsy sample from the individual&#39;s pulmonary artery during progression of the vascular-related disease;   2) obtaining a pulmonary artery sample from a non-diseased control;   3) extracting RNA from the samples in steps 1) and 2);   4) obtaining gene products from the RNA extracted in step 3); and   5) comparing gene expression levels from the biopsy sample with the non-diseased control, and   
           b) associating the genes upregulated in the biopsy sample with an inhibitor of the gene products for administration to the individual and genes downregulated in the biopsy sample with a promoter of the gene products for administration to the individual.       
 
         [0034]    Another aspect of the present invention provides for methods of treating an individual having a vascular-related disease by targeting microRNAs comprising the following steps:
       a) assessing a stage of the vascular-related disease in the individual;   b) identifying whether microRNAs are upregulated or downregulated;   c) selecting the microRNAs to target based on the stage of the vascular-related disease and whether the microRNAs are upregulated or downregulated; and   d) administering an agent known to inhibit an upregulated microRNA or an agent known to promote a downregulated microRNA to the individual. A variation of this embodiment provides for the stage of the vascular-related disease being based on flow rates and blood pressure within an artery of the individual.       
 
         [0039]    Another aspect of the present invention provides for methods of therapeutically targeting microRNA dysregulated in PAH comprising the steps of:
       (a) obtaining a biopsy sample from the pulmonary artery during the progression of PAH;   (b) obtaining a pulmonary artery sample from a non-diseased control;   (c) extracting RNA from the artery samples;   (d) converting the RNA to cDNA;   (e) comparing levels of microRNA expression at the two differing times;   (f) identifying microRNA dysregulated in PAH relative to baseline; and   (g) inhibiting upregulated microRNA or promoting downregulated microRNA identified in PAH biopsies.       
 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0047]      FIG. 1  depicts a surgical shunt model of PAH and its association with congenital heart disease (CHD). 
           [0048]      FIG. 2  depicts the endoarterial biopsy procedural configuration. 
           [0049]      FIG. 3  depicts biopsies: normal vessels at baseline, hypertensive LPA at 7, 21, 60 and 180 days post shunt. 
           [0050]      FIG. 4  depicts GeneSpring downstream analysis of microarray data. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0051]    The model described in the present invention is surgically-induced PAH in pigs. Our model mimics human Eisenmenger syndrome (a form of PAH related to congenital heart malformation) in both symptoms and pathology (Corno et al 2003). The size of the animals makes the pulmonary vessels available to the catheter, providing a ready transition to human clinical use. And finally, the commercial availability of whole genome porcine microarrays (Bai et al 2003) makes the species ideal for our purposes in the study, and renders the use of cross species microarrays unnecessary (Medhora et al 2002). 
         [0052]    By obtaining pulmonary endovascular samples at early, intermediate and late time points in PAH progression, and analyzing these samples using porcine whole genome microarrays, a time-sensitive microarray based map of the underlying molecular biology of PAH may be obtained. Improved knowledge of the molecular mechanisms underlying PAH progression can lead to the identification of stage-specific biomarkers, new therapeutic targets for drug intervention, and novel signaling pathways involved in the pathogenesis of PAH. These novel target genes can then be validated using quantitative PCR and immunohistochemical stains on porcine endoarterial biopsy samples procured concurrently. At the same time, the combination of minimally invasive endoarterial biopsy and whole genome microarray analysis can serve as an animal model for subsequent studies in PAH patients. 
         [0053]    The following examples provided in this disclosure provide a profile gene expression in pulmonary hypertensive pigs by surgical anastomosis of the left pulmonary artery to the descending aorta. Endoarterial biopsy samples are collected from animals with a surgical shunt model of pulmonary hypertension at multiple time points over a 6-month time course. Gene expression analysis of the biopsy samples was performed on porcine microarrays. Microarray analysis was performed to detect dysregulated genes previously unassociated with PAH, discover novel biomarkers of pulmonary hypertension and novel targets for therapeutic intervention and advance knowledge of the molecular mechanisms of pulmonary hypertension. These studies will also help validate a new platform for PAH diagnosis and drug discovery, endoarterial biopsy and microarray analysis, for eventual clinical practice. 
       Examples 
     Example I: Construction of a Microarray-Based Map of Changes in Gene Expression During the Progression of PAH and the Identification of Novel Therapeutic Candidates 
       [0054]    In an animal model of PAH created by Antonio Corno and colleagues, pigs undergo surgery that redirects systemic circulation into the left pulmonary artery mimicking pulmonary hypertension secondary to congenital heart disease. The surgery elevates PA pressure and creates the same hemodynamic conditions that PAH patients experience. The present study investigates how the elevated pressure remodels the pulmonary vasculature. In Corno&#39;s studies, histology on necropsy confirmed intimal hyperplasia in the pulmonary arteries, evidence that the surgical shunt surgery described will cause endovascular remodeling (Corno et al 2003). 
       Biopsy Extraction and Surgery Protocol 
       [0055]    20-30 kg Yucatan Micropigs ( Sus scrofa , Yucatan micro breed) underwent surgical anastomosis of the left pulmonary artery to the descending aorta, resulting in left pulmonary arterial hypertension of at least systemic levels. Animals are penned in the laboratory for no less than one week prior to surgery and fed normal chow. On surgery day, animals were premedicated with 20 mg/kg intramuscular ketamine and 0.1 mg/kg intramuscular midazolam. After 0.25 mg of intramuscular atropine, anesthesia was induced with 1 mg/kg intravenous midazolam and 0.1 mg/kg intravenous fentanyl and maintained with 0.1 mg/kg/hr intravenous pancuronium bromide. Pigs were ventilated with an inspired oxygen fraction (FiO2) of 0.4, a tidal volume of 15 ml/kg, and a respiratory rate of 12 breaths/minute. One gram of intravenous cefazolin was given before and 2 hours after the surgical procedure. Surgical and catheter procedures were performed under general anesthesia with endo-tracheal intubation. Sedation medications and anesthetics were administered by an anesthesiologist. Intra-cardiac and intravascular pressures, EKG, and blood oxygen saturations were monitored continuously. 
         [0056]    Under sterile conditions (the thoracic area was shaved and prepared with betadine, a left thoracotomy was performed through the fourth intercostal space, about 5 centimeters, to expose the great arteries. The main pulmonary artery (MPA) and its branches were identified and freed from surrounding tissue. Two clamps were placed on the proximal left pulmonary artery (LPA). The proximal LPA was sutured closed, using prolene, and the distal LPA was sutured end to side in a clamped region in the descending aorta ( FIG. 1 ), using cardiovascular prolene. Pieces of LPA endoarterial tissue were taken for histology. The clamps were removed and an IV dose of 1 mg/kg Furosemide immediately given. Hemostasis was obtained with sutures and cautery. Direct needle blood pressures were recorded in the main pulmonary artery and in the newly anastomosed left pulmonary artery. The chest was closed with sutures, both subcutaneous and cutaneous layers, using prolene and surgical wire. The animals then were weaned from anesthesia and mechanical ventilation. Postoperative analgesia was provided with morphine four times a day and a 1-2 mg/kg dose from 0.25% solution of IV Bupivacaine, a local anesthetic. A circulating warming blanket was used during surgery and recovery. 
         [0057]    Endoarterial biopsies were performed at baseline prior to surgery to obtain unaffected tissue, and at post-shunt timepoints to obtain hypertensive biopsy samples ( FIG. 2 ). Follow up endoarterial biopsy procedures were scheduled 7, 21, and 180 days after surgery. On each catheterization day, animals were premedicated with 10 mg/kg of IV propofol, were intubated and ventilated at a rate of 12 breaths/min and were maintained under anesthesia with 1.5% halpthane. A femoral artery line was placed for monitoring. To obtain biopsies from the hypertensive left lung, an 8F introducer is placed in a carotid artery, and a 7F endhole catheter is advanced into the aorta. An angiogram is performed to visualize the LPA—aortic anastomosis. The 7F endhole catheter is then threaded through the anastomosis with X-ray fluroscopic guidance. An angiogram of the hypertensive left pulmonary vascular tree is then performed, and the catheter is advanced to the distal pulmonary artery selected for biopsy. A 0.038 in, 260 cm extra stiff Amplatz exchange guide wire will then be passed through the end-hole catheter. The end-hole catheter was exchanged for a long flexible 8F introducer sheath that is adapted with a radio opaque band at the distal end and shaped to conform to the vascular pathway. A 7F angiographic catheter was advanced through the sheath in to a 2.5 mm to 3.0 mm distal pulmonary artery branch, where an angiogram was obtained. The angiographic catheter will serve as a guide to advance the stiff sheath into a small vessel targeted for biopsy and will then be exchanged for the endoarterial biopsy catheter. 
         [0058]    The endoarterial biopsy catheter has an external diameter of 2.5 mm and is composed of two flexible polymeric tubes that slide relative to each other. The inner tube has a stainless steel distal end with a beveled opening that is designed to accommodate arterial tissue. A vacuum is coupled to the inner tube and channeled to the beveled opening. The outer tube terminates in a stainless steel cutting tube. The proximal ends of the two tubes are with a spring powered operating mechanism. To obtain the biopsy sample a vacuum is transmitted to the beveled opening of the inner tube, causing a tissue sample to be drawn in. The outer tube is then advanced over the inner tube, severing the tissue sample. With this design, the area of artery contacted by the outer periphery of the beveled opening is larger than the inner aperture connected to the vacuum, this maintaining the tissue sample with its orientation preserved. After each biopsy, the catheter was removed and the tissue sample was placed in the appropriate solution for further processing and analysis. After the biopsy procedures were completed, repeated angiograms were obtained to assess the degree of vascular injury. At the end of the procedure, the biopsy catheter and introducer sheath were removed and hemostasis was obtained by surgical repair of the carotid artery. The animals will then be weaned from anesthesia and mechanical ventilation. Postoperative analgesia was provided with morphine four times a day and or fentanyl patches and non-steroidal anti-inflammatory drugs four times a day. 
       Tissue Processing 
       [0059]    For microarray analysis, biopsy samples are placed in a test tube containing RNAlater (Qiagen), flash frozen in dry ice, and kept frozen until RNA extraction. Additional samples are preserved in formalin, OCT freezing solution, or Bouin&#39;s solution for subsequent immunohistochemical and quantitative PCR analysis. 
       Porcine Genome Arrays 
       [0060]    The Affymetrix GeneChip® Porcine Genome Array provides comprehensive coverage of the  Sus scrofa  transcriptome. The array contains 23,937 probe sets that interrogate approximately 23,256 transcripts from 20,201  Sus scrofa  genes. 
         [0061]    The sequence information for this array was selected from public data sources including UniGene Build 28 (August 2004), GenBank® mRNAs up to Aug. 24, 2004, and GenBank® porcine mitochondrial and rRNA sequences. Probe sets consist of up to eleven probe pairs. The array format consists of eleven micron features synthesized on the 100 format. 
         [0000]    RNA Extraction from Endoarterial Biopsy Samples 
         [0062]    RNA was prepared from fresh frozen endoarterial biopsy samples in a segregated laboratory, specially prepared and cleaned regularly to destroy nucleases. Specimens were homogenized using QIAshredder columns (Qiagen, Valencia, Calif.) utilized in a FastPrep FP120 Homogenizer (Thermo Electron Corporation, Waltham, Mass.). RNA was isolated using RNeasy Mini columns (Qiagen, Valencia, Calif.) as per manufacturer&#39;s protocol. All total RNA was eluted in nuclease free water, and quantity was established by UV spectrophotometer. Final RNA integrity was evaluated by capillary electrophoresis on the Agilent 2100 Bioanalyzer (Agilent, Palo Alto, Calif.). 
       Gene Expression 
       [0063]    Before target production, the quality and quantity of each RNA sample was assessed using a 2100 BioAnalyzer (Agilent). Target was prepared and hybridized according to the “Affymetrix Technical Manual”. Total RNA (ug) was converted into cDNA using Reverse Transcriptase (Invitrogen) and a modified oligo (dT)24 primer that contains T7 promoter sequences (GenSet). After first strand synthesis, residual RNA was degraded by the addition of RNaseH and a double-stranded cDNA molecule was generated using DNA Polymerase I and DNA Ligase. The cDNA will then be purified and concentrated using a phenol:chloroform extraction followed by ethanol precipitation. The cDNA products will then be incubated with T7 RNA Polymerase and biotinylated ribonucleotides using an In Vitro Transcription kit (Enzo Diagnostics). One-half of the cRNA product was purified using an RNeasy column (Qiagen) and quantified with a spectrophotometer. The cRNA target (20 ug) was incubated at 94° C. for 35 minutes in fragmentation buffer (Tris, MgOAc, KOAc). The fragmented cRNA was diluted in hybridization buffer (MES, NaCl, EDTA, Tween 20, Herring Sperm DNA, Acetylated BSA) containing biotin-labeled OligoB2 and Eukaryotic Hybridization Controls (Affymetrix). The hybridization cocktail was denatured at 99° C. for 5 minutes, incubated at 45° C. for 5 minutes and then injected into a GeneChip® cartridge. The GeneChip® array was incubated at 42° C. for at least 16 hours in a rotating oven at 60 rpm. GeneChips® were washed with a series of nonstringent (25° C.) and stringent (50° C.) solutions containing variable amounts of MES, Tween20 and SSPE. The microarrays will then be stained with Streptavidin Phycoerythrin and the fluorescent signal was amplified using a biotinylated antibody solution. Fluorescent images were detected in a GeneChip® Scanner 3000 and expression data was extracted using the GeneChip® Operating System v 1.1 (Affymetrix). All GeneChips® were scaled to a median intensity setting of 500. Gene expression levels were compared between biopsy samples taken from the control distal pulmonary vasculature (baseline LPA and RPA) and PAH distal pulmonary arteries (surgical shunt LPA). 
       Gene Expression Analysis 
       [0064]    After RNA preparation, array hybridization and scanning of the Porcine GeneChips® exactly as recommended by Affymetrix, the data produced are processed using the Affymetrix tools in the R-Bioconductor package called /Affy/. This tool set allows for various probe level analyses of the data as well as probe level quality control. The MASS algorithm was used, taking into account both the MM and PM probe data, and generating “Present” or “Absent” calls for each gene on each chip. If boxplots of the porcine probe level data reveal that any of the hybridizations are of low quality, the data from these chips was removed from any downstream analysis. MASS with the non-linear Quantiles normalization (Affy package /normalize.quantiles)/ was used with this data set to produce data almost free of artificial correlations. The Present/Absent calls are also used to remove from the analysis the genes that were never expressed in any of the samples examined (this is analogous to using a P-value for gauging a gene&#39;s data quality on a chip, and then filtering). 
         [0065]    Based on the first dozen chips processed, after normalization and quality control ˜19,000 genes were moved on to the next stage of the analysis. The commercial package GeneSpring was used to assess differential gene expression and perform tests using clustering algorithms. Thus far, hierarchical clustering has revealed that the time-point replicates have the greatest similarity to one another. 
         [0066]    Gene expression fold changes for 7, 21 60 and 180 days post-surgery relative to baseline were then loaded into GSEA (gene set enrichment analysis) or specially written PERL scripts which carry out KS (Kolmogorov-Smirnov) statistical analysis in order to identify novel therapeutic candidates. 
       Novel Therapeutic Identification 
       [0067]    During PAH the best therapeutic targets are those which are upregulated as the disease state progresses. Thus drugs which are known to counter the action of any upregulated genes and their products would be of the greatest potential therapeutic value. Therefore, lists of upregulated genes were then matched to drugs which target their gene products. 
         [0068]    In addition, many drugs interact with multiple targets in the body&#39;s tissues. Lists of the targets (called genesets) for each of ˜2000 characterized drugs were obtained from the literature and online databases. These genesets were then used to search for drugs which would be most likely to have therapeutic value in PAH. 
         [0069]    This was done by using KS statistics which computes the Kolmogorov-Smirnov score for a geneset for a particular drug within an ordered list. The KSscore task is used to examine the enrichment of a set of genes at the top of an ordered list. The KS score is high when the tags appear early (i.e. near the top) of the ordered list. The significance of the KS score for a particular test may be examined by computing KS scores for multiple sets of X query genes selected at random from the dataset (note that the KS score is not independent of the number of members of the query gene set). Using this approach we were able to identify in our messenger RNA expression dataset drugs which are currently used as therapeutics for PAH (see  FIG. 1A ). Importantly, using the same approach we were also able to identify additional potential therapeutics, within the existing pool of characterized drugs. This process identified existing drugs as novel therapeutics for PAH. 
       Example II: Gene Expression Analysis from Porcine Animal Model Data 
     Gene Expression Analysis 
       [0070]    The porcine studies indicate that single endoarterial biopsy samples obtained in the porcine model of surgical shunt PAH contain sufficient RNA for microarray analysis, as we were able to analyze the mRNAs in whole genome porcine microarrays. We obtained endoarterial biopsies and measured pulmonary arterial pressure (PAP) at baseline prior to surgery, and at approximately 7, 21, 60 and 180 days post-PAH surgery from several animals. Porcine whole genome expression values were obtained for biological replicates with 2 samples from each time point. These replicates produced 5 sets of high quality replicated expression data (baseline, day 7, day 21, day 60 and day 180; see Table 1 for PAP data). Downstream data analysis was carried out using commercial (Ingenuity; GeneSpring) and free/open source software (R; Bioconductor; GSEA). Mean expression values were obtained for each gene by averaging the gene expression values of the two biopsies at each timepoint. The resulting gene expression mean values were used to calculate fold changes between day 7, 21, 60 and day 180 gene expression relative to baseline. 
         [0071]    Validity of the model was confirmed by examining the gene expression changes for selected genes previously found to be dysregulated in PAH (Table 2). Endothelin 1 and protein-tyrosine kinase Tie2 both displayed upregulation in accordance with explanted tissue from IPAH transplant recipients (Dewatcher et al 2006), and platelet-derived growth factor receptor alpha, serotonin receptors 2B and 1D, calmodulin, transcription factor STAT5b, voltage-dependent anion channels 1, 2 and 3, and RAS p21 protein activator 1 also increased in our model while tumor necrosis factor and plasminogen activator inhibitor-1 were found to be downregulated in our model in a similar fashion with IPAH explant tissue results (Fantozzi et al 2005). Survivin was upregulated in our model in a similar fashion to published findings (McMurtry et al 2005), and FYN and VAV-1 oncogenes, requiem homolog, inward rectifier K+ channel, and chloride channel 1 also increased while DEAD/H box polypeptide 3 and angiopoietin 1 displayed decreased expression in agreement with patient findings (Geraci et al 2001). We also observed decreased expression of peroxisome proliferator-activated receptor gamma (Ameshima et al 2003), and downregulated vascular endothelial growth factor B (Louzier et al 2003) in correspondence with previous results. The concordance between genes previously found to be aberrant in published PAH studies and altered gene expression in our model attest to the validity and potential usefulness of gene expression data derived from endoarterial biopsies. The time dependent nature of gene expression dysregulation found in our model further demonstrates the utility of obtaining endoarterial biopsies at multiple time points in PAH progression. 
         [0072]    While several of these genes have been previously associated with PAH (for example, KCBN1, CASP3, TLR4, IL1B, IL6, HMGCR, TOP1, FYN, PRKCA, EDNRB, PDGFRA, and HRT2B), several have not (for example, HSPE, YES1, CFTR, MAOA, MAOB, and CACND21), raising the intriguing possibility that known existing drugs that target upregulated genes previously unassociated with PAH may be effective in treatment of the disease. 
       Example III: Identification of Dysregulated microRNA During the Progression of PAH 
       [0073]    Endoarterial biopsy samples percutaneously obtained during the progression of PAH were analyzed to correlate changes in microRNA expression to disease progression. 
         [0000]    microRNA Expression Data Analysis 
         [0074]    Data analysis was done in three stages. First, expression intensities were calculated for each miRNA probed on the array for all hybridizations (12 in total) using illumina&#39;s Beadstudio Version 3.0 software. Second, intensity values were quality controlled and normalized: quality control was carried out by using the illumina Beadstudio detection P-value set to &lt;0.05 as a cutoff. This removed miRNAs which were effectively absent from the arrays (that is, were never detected). After this step, the initial 1145 miRNAs were reduced to 1094. All the arrays were then normalized using the normalize.quantiles routine from the Affy package in Bioconductor. This procedure accounted for any variation in hybridization intensity between the individual arrays 
         [0075]    Finally, these normalized data were imported into GeneSpring and analysed for differentially expressed miRNAs. The groups of biological replicates were described to the software and significantly differentially expressed genes determined on the basis of Welch t-tests and fold difference changes in expression level. The determination of miRNA targets genes was done using a publicly available database of miRNA target sequences and a specially written PERL programming script. 
         [0000]    miRNA Pressure Related Analysis 
         [0076]    The data was also looked at to reflect the stages of the disease (based on blood pressure and flow rates), as opposed to the time point or the individual pigs. Three groups were defined (1) Normal (baseline); (2) High Flow Low Pressure ‘HFLP’ and (3) High Flow High Pressure ‘HFHP’ (see Table 11). The groups were compared back to the baseline and the statistically significantly differentially regulated miRNAs determined (Tables 12, 13, 14 &amp; 15). 
         [0077]    Using illumina microRNA expression microarrays, fluctuations in the level of expression of 1200 microRNAs were determined during the onset and progression of PAH. Porcine and  Homo sapiens  miRNA sequences are very often highly conserved. Expression comparisons were done on a timepoint basis, taking in account the available replicates and the statistical significance of the expression changes. The data was also looked at to reflect the stages of the disease (based on blood pressure and flow rates), as opposed to the time point or the individual pigs. Three groups were defined (1) Normal (baseline); (2) High Flow Low Pressure ‘HFLP’ and (3) High Flow High Pressure ‘HFHP’. The groups were compared back to the baseline and the statistically significantly differentially regulated miRNAs determined. 
         [0000]    Finding Micro RNAs with Potential as Therapeutic Targets 
         [0078]    The messenger RNA expression data set was analysed looking for expression changes in sets of genes with known target sites for particular miRNAs. miRNAs are known to negatively regulate gene expression at the level of translation by binding to upstream regions of mRNA and blocking events required for translation of the mRNA into protein. This was again done using Gene Set Enrichment Analysis (GSEA) and the publicly available miRNA genesets. “Cross-talk” is seen between the messenger RNA gene expression changes and the microRNA expression changes. The messenger RNA expression analysis directly revealed the differential expression of groups of genes competent to be regulated by these miRNA. 
       Example IV: Personalizing Therapeutic Regimens for Vascular-Based Diseases 
       [0079]    The use of gene expression data to shape individual drug therapies has been postulated as the next phase in personalized medicine. The bioinformatic processing of an individual&#39;s gene expression data can be used to generate a ranked list of therapies suitable for that individual. PAH disease pathology varies greatly over time, and is also likely to be specific for particular individuals. The analysis of the RNA in the PAH biopsy samples allows therapies to be tailored to the individual at that particular stage of the diseases progression. 
         [0080]    The genes and biochemical pathways changing the most at the level of gene expression can be determined by comparing the PAH biopsy samples to a baseline control of normal healthy vasculature tissue. Observations show time-dependent extensive changes in gene expression with the progression of PAH. Known targets for approved PAH therapeutics can be seen Up-regulated in the diseased state. 
         [0081]    Drug therapies can be ranked by using the known targets of drugs as genesets. These drug signature lists can then be used in a process such as Gene Set Enrichment Analysis, or KS statistics. KS Statistics returns a score for how well ranked a particular drug would be for a particular patient. 
         [0082]    A drug is represented as the set of its known target genes; this can be in the dozens for some bioactive compounds. Genesets for ˜2000 drugs were assembled. KS Statistics yields a value (‘KS score’) representing the positional distribution of the set of query genes (here, the drug targets) within an ordered list of genes (genes induced in PAH). The ordered list is produced by looking at the fold change in a mRNAs expression between time X and the baseline, and sorting on this value. The gene with the greatest fold change is ranked as #1, second greatest fold change is ranked as #2, etc. KS score is computed in accordance with the Kolmogorov-Smirnov non-parametric rank statistic where X is the number of genes in the query gene set, Z is the number of genes in the ordered list, and Y=Z−X. A suitable baseline is generated using gene expression from artery samples from non-diseased controls. These samples can be obtained surgically, percutaneously or post-mortem. 
         [0083]    This process can be repeated for all the PAH time points and the resulting table of KS scores for each drug hierarchically clustered. This reveals which drugs are potentially of the greatest therapeutic value for a patient. 
         [0084]    This supports the idea of achieving personalized treatments for vascular-based diseases by generating individualized drug prescriptions based on the bioinformatic processing of gene expression data from endoarterial biopsy samples obtained from diseased arteries. Similarly, this enables personalized treatments for vascular-based diseases by generating lists of dysregulated microRNA from the bioinformatic processing of microRNA expression data from endoarterial biopsy samples from diseased arteries. 
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Pulmonary arterial pressures obtained during endoarterial biopsy 
               
               
                 catheterization for biopsy samples used in microarray analysis. 
               
             
          
           
               
                   
                 Pulmonary Arterial Pressure mmHg 
               
             
          
           
               
                   
                 Biopsy Sample 
                 Systolic 
                 Diastolic 
                 Mean 
               
               
                   
                   
               
               
                   
                 Baseline Pig #9 
                 22 
                 11 
                 17 
               
               
                   
                 Baseline Pig #10 
                 25 
                 16 
                 18 
               
               
                   
                 Day 21 Pig #2 
                 95 
                 66 
                 82 
               
               
                   
                 Day 21 Pig #6 
                 41 
                 26 
                 33 
               
               
                   
                 Day 60 Pig #6 
                 87 
                 59 
                 74 
               
               
                   
                 Day 60 Pig #5 
                 49 
                 27 
                 38 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Selected genes previously associated with PAH similarly dysregulated in the porcine model. 
               
             
          
           
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 Fold 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Fold 
                 Fold 
                 Fold 
                 Change 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Change 
                 Change 
                 Change 
                 Day 
               
               
                 Gene 
                   
                   
                   
                   
                   
                   
                 Day 
                 Day 
                 Day 
                 180/ 
               
               
                 Symbol 
                 Name 
                 Baseline 
                 Day 7 
                 Day 21 
                 Day 60 
                 Day 180 
                 7/Base 
                 21/Base 
                 60/Base 
                 Base 
               
               
                   
               
             
          
           
               
                 VAV1 
                 vav 1 oncogene 
                 32.56 
                 21.65 
                 237.16 
                 138.29 
                 15.39 
                 −1.50 
                 7.28 
                 4.25 
                 −2.12 
               
               
                 RASA1 
                 RAS p21 protein 
                 73.23 
                 388.68 
                 280.27 
                 704.56 
                 361.25 
                 5.31 
                 3.83 
                 9.62 
                 4.93 
               
               
                   
                 activator 1 
               
               
                 TIE2 
                 protein-tyrosine 
                 20.92 
                 2.59 
                 32.46 
                 702.68 
                 218.34 
                 −8.08 
                 1.55 
                 33.59 
                 10.44 
               
               
                   
                 kinase Tie2 
               
               
                 FYN 
                 fyn proto- 
                 43.33 
                 180.38 
                 404.77 
                 531.03 
                 166.17 
                 4.16 
                 9.34 
                 12.26 
                 3.83 
               
               
                   
                 oncogene 
               
               
                 VDAC1 
                 voltage-dependent 
                 1176.57 
                 2350.33 
                 6629.76 
                 3144.14 
                 2277.10 
                 2.00 
                 5.63 
                 2.67 
                 1.94 
               
               
                   
                 anion channel 1 
               
               
                 PDGFRA 
                 platelet-derived 
                 69.46 
                 152.75 
                 10.45 
                 611.81 
                 18.80 
                 2.20 
                 −6.64 
                 8.81 
                 −3.69 
               
               
                   
                 growth factor 
               
               
                   
                 receptor alpha 
               
               
                 5-HT2B 
                 serotonin 2B 
                 49.96 
                 19.03 
                 166.45 
                 142.91 
                 488.77 
                 −2.63 
                 3.33 
                 2.86 
                 9.78 
               
               
                   
                 receptor 
               
               
                 KCNJ2 
                 inwardly 
                 389.66 
                 83.23 
                 1059.11 
                 212.29 
                 84.28 
                 −4.68 
                 2.72 
                 −1.84 
                 −4.62 
               
               
                   
                 rectifying 
               
               
                   
                 potassium 
               
               
                   
                 channel KIR6.1 
               
               
                 5-HT1D 
                 serotonin 1D 
                 14.17 
                 42.48 
                 8.32 
                 61.48 
                 4.95 
                 3.00 
                 −1.70 
                 4.34 
                 −2.86 
               
               
                   
                 receptor 
               
               
                 DPF2 
                 requiem, 
                 140.95 
                 123.89 
                 140.90 
                 195.55 
                 93.92 
                 −1.14 
                 −1.00 
                 1.39 
                 −1.50 
               
               
                   
                 apoptosis 
               
               
                   
                 response zinc 
               
               
                   
                 finger gene 
               
               
                 VDAC2 
                 Voltage- 
                 5683.09 
                 2665.62 
                 1620.37 
                 4940.32 
                 3643.38 
                 −2.13 
                 −3.51 
                 −1.15 
                 −1.56 
               
               
                   
                 dependent 
               
               
                   
                 anion channel 2 
               
               
                 STAT5B 
                 signal transducer 
                 469.40 
                 571.47 
                 1327.53 
                 808.09 
                 626.07 
                 1.22 
                 2.83 
                 1.72 
                 1.33 
               
               
                   
                 and activator of 
               
               
                   
                 transcription 5b 
               
               
                 AGPT 
                 angiopoietin 1 
                 17.825026 
                 50.240685 
                 11.806807 
                 70.12715 
                 3.4479218 
                 2.82 
                 −1.51 
                 3.93 
                 −5.17 
               
               
                 BIRC5 
                 apoptosis 
                 169.33 
                 751.37 
                 140.45 
                 31.26 
                 44.69 
                 4.44 
                 −1.21 
                 −5.42 
                 −3.79 
               
               
                   
                 inhibitor survivin 
               
               
                 VDAC3 
                 voltage-dependent 
                 4092.99 
                 750.86 
                 5013.26 
                 959.72 
                 2018.55 
                 −5.45 
                 1.22 
                 −4.26 
                 −2.03 
               
               
                   
                 anion channel 3 
               
               
                 PLANH1 
                 plasminogen 
                 27760.742 
                 43007.71 
                 23685.375 
                 28771.838 
                 36086.305 
                 1.55 
                 −1.17 
                 1.04 
                 1.30 
               
               
                   
                 activator 
               
               
                   
                 inhibitor I 
               
               
                 PPARG 
                 peroxisome 
                 177.80 
                 12.86 
                 18.96 
                 194.20 
                 62.40 
                 −13.83 
                 −9.38 
                 1.09 
                 −2.85 
               
               
                   
                 proliferator- 
               
               
                   
                 activated receptor 
               
               
                   
                 gamma 2 
               
               
                 CALM1 
                 Calmodulin 
                 3092.78 
                 2436.23 
                 867.25 
                 1401.38 
                 2252.81 
                 −1.27 
                 −3.57 
                 −2.21 
                 −1.37 
               
               
                 APOE 
                 apolipoprotein E 
                 358.91 
                 206.34 
                 94.35 
                 129.60 
                 288.79 
                 −1.74 
                 −3.80 
                 −2.77 
                 −1.24 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Day 7 prescription. 
               
             
          
           
               
                   
                   
                 Fold 
                 Fold 
                 Fold 
                 Fold 
                   
                   
               
               
                   
                   
                 Change 
                 Change 
                 Change 
                 Change 
               
               
                   
                   
                 D7/ 
                 D21/ 
                 D60/ 
                 D180/ 
                 Gene 
               
               
                 Probe ID 
                 Name 
                 Base 
                 Base 
                 Base 
                 Base 
                 Symbol 
                 DRUGS 
               
               
                   
               
             
          
           
               
                 Ssc.11018.1.A1_at 
                 Mitogen-activated protein 
                 39.80 
                 −5.02 
                 −17.27 
                 −20.43 
                 MAPK14 
                 SCIO-469, RO-3201195 
               
               
                   
                 kinase 14 
               
               
                 Ssc.15986.1.S1_at 
                 Insulin receptor 
                 29.28 
                 −16.85 
                 −17.70 
                 −19.01 
                 INSR 
                 insulin, insulin aspart, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 insulin glulisine, insulin 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lispro, insulin glargine 
               
               
                 Ssc.873.1.S1_at 
                 Cell division control protein 2 
                 27.38 
                 −2.37 
                 −4.66 
                 −7.76 
                 CDC2 
                 flavopiridol 
               
               
                 Ssc.29928.1.A1_at 
                 Histone deacetylase 11 (HD11) 
                 21.56 
                 −3.17 
                 −2.91 
                 −10.50 
                 HDAC11 
                 tributyrin, PXD101, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pyroxamide, vorinostat, FR 
               
               
                   
                   
                   
                   
                   
                   
                   
                 901228 
               
               
                 Ssc.100.1.S1_at 
                 Tumor necrosis factor 
                 18.41 
                 −1.70 
                 −9.62 
                 −3.15 
                 TNF 
                 adalimumab, etanercept, 
               
               
                   
                 precursor (TNF-alpha) 
                   
                   
                   
                   
                   
                 infliximab, CDP870, golimumab, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 thalidomide 
               
               
                 Ssc.19672.1.S1_at 
                 RAC-alpha serine/threonine- 
                 17.77 
                 1.25 
                 −19.82 
                 −2.11 
                 AKT1 
                 enzastaurin 
               
               
                   
                 protein kinase 
               
               
                 Ssc.14475.3.S1_a_at 
                 Peroxisome proliferator 
                 13.83 
                 −9.38 
                 1.09 
                 −2.85 
                 PPARG 
                 rosiglitazone, GI262570, 
               
               
                   
                 activated receptor gamma 
                   
                   
                   
                   
                   
                 pioglitazone, tesaglitazar, 
               
               
                   
                 (PPAR-gamma) 
                   
                   
                   
                   
                   
                 troglitazone 
               
               
                 Ssc.14326.1.A1_at 
                 Mitogen-activated protein 
                 12.63 
                 1.56 
                 −1.80 
                 −7.24 
                 MAPK13 
                 SCIO-469 
               
               
                   
                 kinase 13 
               
               
                 Ssc.25843.1.S1_at 
                 Chloride channel protein 2 
                 11.77 
                 −17.04 
                 −21.97 
                 −9.92 
                 CLCN2 
                 lubiprostone 
               
               
                   
                 (ClC-2 
               
               
                 Ssc.16201.1.A1_at 
                 Metabotropic glutamate 
                 10.79 
                 −35.68 
                 −33.34 
                 −47.92 
                 GRM7 
                 fasoracetam 
               
               
                   
                 receptor 
               
               
                 Ssc.11381.1.S1_at 
                 Interferon-alpha/beta receptor 
                 10.45 
                 8.08 
                 2.61 
                 −1.30 
                 IFNAR1 
                 interferon beta-1a, interferon 
               
               
                   
                 alpha chain 
                   
                   
                   
                   
                   
                 alfa-2b, interferon alfacon-1, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 PEG-interferon alfa-2a, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a/ribavirin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegintron, interferon beta-1b, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 IFNA2A 
               
               
                 Ssc.5371.1.S1_a_at 
                 DNA polymerase epsilon subunit 
                 10.16 
                 1.68 
                 −1.37 
                 −3.14 
                 POLE2 
                 gemcitabine 
               
               
                   
                 B (DNA polymerase II subunit 
               
               
                   
                 B) 
               
               
                 Ssc.14471.1.S1_at 
                 B-lymphocyte antigen CD19 
                 9.54 
                 3.30 
                 −10.32 
                 3.04 
                 CD19 
                 combotox, HD37-dgRTA, MT103 
               
               
                 Ssc.24856.1.A1_at 
                 phosphodiesterase 11A; cyclic 
                 9.36 
                 −2.70 
                 −3.68 
                 −2.68 
                 PDE11A 
                 dyphylline, nitroglycerin, 
               
               
                   
                 nucleotide phosphodiesterase 
                   
                   
                   
                   
                   
                 aminophylline, dipyridamole, 
               
               
                   
                 11A1 
                   
                   
                   
                   
                   
                 tolbutamide, tadalafil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline 
               
               
                 Ssc.189.1.S1_at 
                 Diacylglycerol O- 
                 9.16 
                 −4.21 
                 −36.07 
                 −24.06 
                 DGAT1 
                 omacor 
               
               
                   
                 acyltransferase 1 
               
               
                 Ssc.16186.1.S1_at 
                 T-cell surface glycoprotein 
                 9.00 
                 3.12 
                 2.12 
                 −5.66 
                 CD3E 
                 visilizumab, MT103, muromonab- 
               
               
                   
                 CD3 epsilon 
                   
                   
                   
                   
                   
                 CD3 
               
               
                 Ssc.15601.1.A1_s_at 
                 Interleukin-1 beta precursor 
                 8.18 
                 4.65 
                 −14.71 
                 −2.84 
                 IL1B 
                 IL-1 trap 
               
               
                   
                 (IL-1 beta) 
               
               
                 Ssc.5538.1.S1_at 
                 Carbonic anhydrase II 
                 8.09 
                 1.39 
                 −2.25 
                 −1.35 
                 CA2 
                 methazolamide, 
               
               
                   
                 (Carbonate dehydratase II) 
                   
                   
                   
                   
                   
                 hydrochlorothiazide, 
               
               
                   
                 (CA-II) (Carbonic anhydrase 
                   
                   
                   
                   
                   
                 acetazolamide, 
               
               
                   
                 C)] 
                   
                   
                   
                   
                   
                 trichloromethiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dorzolamide, chlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dorzolamide/timolol, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brinzolamide, chlorthalidone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benzthiazide, sulfacetamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 topiramate 
               
               
                 Ssc.113.1.S1_at 
                 Interleukin-1 alpha (IL-1 
                 8.01 
                 −2.65 
                 −1.59 
                 −7.73 
                 IL1A 
                 IL-1 trap 
               
               
                   
                 alpha) 
               
               
                 Ssc.2895.1.S1_at 
                 Serine/threonine-protein 
                 7.48 
                 −2.02 
                 −2.45 
                 −1.81 
                 AURKB 
                 AZD-1152 
               
               
                   
                 kinase 
               
               
                 Ssc.8219.1.A1_at 
                 Histone deacetylase 8 (HD8) 
                 7.21 
                 −2.18 
                 −12.09 
                 −29.63 
                 HDAC8 
                 tributyrin, PXD101, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pyroxamide, vorinostat, FR 
               
               
                   
                   
                   
                   
                   
                   
                   
                 901228 
               
               
                 Ssc.13473.1.A1_at 
                 Ceramide glucosyltransferase 
                 7.13 
                 −2.88 
                 −4.17 
                 −6.14 
                 UGCG 
                 N- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 butyldeoxygalactonojirimycin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 N-butyldeoxynojirimycin 
               
               
                 Ssc.14129.1.A1_at 
                 4-aminobutyrate 
                 6.91 
                 2.56 
                 −21.17 
                 −3.35 
                 ABAT 
                 valproic acid 
               
               
                   
                 aminotransferase, 
               
               
                   
                 mitochondrial (GABA 
               
               
                   
                 transaminase) 
               
               
                 Ssc.15379.1.S1_at 
                 diacylglycerol O- 
                 6.60 
                 −1.51 
                 −3.49 
                 −2.13 
                 DGAT2 
                 omacor 
               
               
                   
                 acyltransferase homolog 2; 
               
               
                   
                 GS1999full 
               
               
                 Ssc.15830.1.A1_at 
                 Retinoic acid receptor beta 
                 6.60 
                 −3.28 
                 −1.83 
                 −1.10 
                 RARB 
                 etretinate, adapalene, 13-cis- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 retinoic acid, tazarotene, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 acitretin, retinoic acid, 9- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cis-retinoic acid, fenretinide 
               
               
                 Ssc.17928.1.A1_at 
                 helicase (DNA) B; helicase B 
                 6.40 
                 −2.65 
                 −4.38 
                 −1.06 
                 HELB 
                 epirubicin 
               
               
                 Ssc.19673.1.S1_at 
                 T-cell surface glycoprotein 
                 6.40 
                 2.70 
                 2.03 
                 −11.77 
                 CD3D 
                 visilizumab, MT103 
               
               
                   
                 CD3 delta 
               
               
                 Ssc.17222.1.A1_at 
                 mucin 1, transmembrane; 
                 6.31 
                 −6.10 
                 −5.94 
                 −13.48 
                 MUC1 
                 HuHMFG1 
               
               
                 Ssc.55.1.S1_at 
                 Epidermal growth factor 
                 6.09 
                 −5.46 
                 −4.68 
                 −4.52 
                 EGFR 
                 cetuximab, AEE 788, 
               
               
                   
                 receptor 
                   
                   
                   
                   
                   
                 panitumumab, BMS-599626, ARRY- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 334543, XL647, canertinib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 gefitinib, HKI-272, PD 153035, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lapatinib, vandetanib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 erlotinib 
               
               
                 Ssc.19059.1.A1_at 
                 Type-1 angiotensin II receptor 
                 5.57 
                 −2.57 
                 1.50 
                 −11.08 
                 AGTR1 
                 amlodipine/olmesartan 
               
               
                   
                 (AT1) (AT1AR 
                   
                   
                   
                   
                   
                 medoxomil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 losartan/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 valsartan/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 candesartan cilexetil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 olmesartan medoxomil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 irbesartan, losartan potassium, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 telmisartan, eprosartan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 candesartan 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cilexetil/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/irbesartan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 eprosartan/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/telmisartan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/olmesartan 
               
               
                   
                   
                   
                   
                   
                   
                   
                 medoxomil, valsartan 
               
               
                 Ssc.16162.1.S1_at 
                 4-hydroxyphenylpyruvate 
                 5.43 
                 −8.93 
                 −8.65 
                 −3.84 
                 HPD 
                 nitisinone 
               
               
                   
                 dioxygenase 
               
               
                 Ssc.27603.1.S1_at 
                 Endothelin B receptor 
                 5.30 
                 −3.27 
                 15.99 
                 1.23 
                 EDNRB 
                 bosentan, sitaxsentan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 atrasentan 
               
               
                 Ssc.16333.1.A1_at 
                 Multidrug resistance protein 1 
                 4.94 
                 −2.99 
                 −3.50 
                 −22.89 
                 ABCB1 
                 XR9576, OC 144-093, valspodar 
               
               
                 Ssc.12769.1.A1_at 
                 Amiloride-sensitive cation 
                 4.82 
                 −13.74 
                 −9.59 
                 −10.72 
                 ACCN1 
                 amiloride, 
               
               
                   
                 channel 1, neuronal 
                   
                   
                   
                   
                   
                 amiloride/hydrochlorothiazide 
               
               
                 Ssc.17155.1.A1_at 
                 heparanase; heparanase-1 
                 4.81 
                 5.38 
                 2.98 
                 −1.83 
                 HPSE 
                 heparanase inhibitor PI-88 
               
               
                 Ssc.15933.1.S1_s_at 
                 Cytotoxic T-lymphocyte protein 
                 4.76 
                 −5.14 
                 −6.63 
                 −26.39 
                 CTLA4 
                 ipilimumab, ticilimumab 
               
               
                   
                 4 (Cytotoxic T-lymphocyte- 
               
               
                   
                 associated antigen 4) (CTLA-4) 
               
               
                   
                 (CD152 antigen) 
               
               
                 Ssc.15965.1.S1_at 
                 Inward rectifier potassium 
                 4.68 
                 2.72 
                 −1.84 
                 −4.62 
                 KCNJ2 
                 nicorandil, amiodarone 
               
               
                   
                 channel 2 (IRK1) 
               
               
                 Ssc.26351.1.S1_at 
                 cAMP-specific 3′,5′-cyclic 
                 4.67 
                 4.99 
                 3.61 
                 −1.15 
                 PDE4D 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase 4D 
                   
                   
                   
                   
                   
                 arofylline, tetomilast, L 
               
               
                   
                   
                   
                   
                   
                   
                   
                 869298, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 anagrelide, cilomilast, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 milrinone, rolipram, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 caffeine 
               
               
                 Ssc.15990.1.A1_at 
                 Retinoic acid receptor RXR- 
                 4.42 
                 −4.18 
                 −18.45 
                 −24.58 
                 RXRA 
                 bexarotene, retinoic acid, 9- 
               
               
                   
                 alpha 
                   
                   
                   
                   
                   
                 cis-retinoic acid 
               
               
                 Ssc.2605.1.A1_at 
                 Protein farnesyltransferase 
                 4.39 
                 −2.62 
                 −7.00 
                 −2.74 
                 FNTB 
                 lonafarnib, tipifarnib 
               
               
                   
                 beta 
               
               
                 Ssc.30373.1.A1_at 
                 cGMP-specific 3′,5′-cyclic 
                 4.27 
                 1.52 
                 2.34 
                 4.09 
                 PDE5A 
                 dyphylline, nitroglycerin, DA- 
               
               
                   
                 phosphodiesterase 
                   
                   
                   
                   
                   
                 8159, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 sildenafil, dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aspirin/dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vardenafil, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tadalafil, theophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline 
               
               
                 Ssc.19233.1.S1_at 
                 Collagen alpha 2(IX) chain 
                 4.23 
                 −1.14 
                 −22.83 
                 −2.12 
                 COL9A2 
                 collagenase 
               
               
                 Ssc.1147.1.A1_at 
                 Lipoprotein lipase 
                 4.05 
                 −5.49 
                 3.78 
                 −8.08 
                 LPL 
                 nicotinic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lovastatin/niacin 
               
               
                 Ssc.13160.1.A1_at 
                 Voltage-dependent L-type 
                 4.03 
                 −4.75 
                 −1.11 
                 −2.77 
                 CACNA1F 
                 MEM-1003, mibefradil, 
               
               
                   
                 calcium channel alpha-1F 
                   
                   
                   
                   
                   
                 bepridil, nisoldipine, 
               
               
                   
                 subunit 
                   
                   
                   
                   
                   
                 isradipine, nicardipine 
               
               
                 Ssc.12748.1.A1_at 
                 Catechol O-methyltransferase, 
                 4.03 
                 −3.20 
                 −5.82 
                 −21.93 
                 COMT 
                 carbidopa/entacapone/levodopa, 
               
               
                   
                 membrane-bound form 
                   
                   
                   
                   
                   
                 BIA-3-202, tolcapone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 entacapone 
               
               
                 Ssc.24986.1.S1_at 
                 Aldehyde dehydrogenase 1A1 
                 4.00 
                 −3.76 
                 −2.17 
                 −9.20 
                 ALDH1A1 
                 disulfiram, chlorpropamide 
               
               
                 Ssc.15972.1.S1_at 
                 Peroxisome proliferator 
                 3.83 
                 −1.07 
                 −2.73 
                 −1.60 
                 PPARD 
                 GW501516 
               
               
                   
                 activated receptor delta 
               
               
                   
                 (PPAR-delta) 
               
               
                 Ssc.24509.1.A1_at 
                 Gamma-aminobutyric-acid 
                 3.76 
                 −1.28 
                 −1.98 
                 −1.23 
                 GABRP 
                 alphadolone, sevoflurane, 
               
               
                   
                 receptor pi subunit 
                   
                   
                   
                   
                   
                 isoflurane, isoniazid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 felbamate, etomidate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 halothane, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fluoxetine/olanzapine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 eszopiclone, zolpidem, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lorazepam, olanzapine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 zaleplon, secobarbital, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 phenobarbital, pentobarbital, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 desflurane, methoxyflurane, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enflurane 
               
               
                 Ssc.7176.1.A1_at 
                 C—X—C chemokine receptor type 
                 3.74 
                 10.91 
                 8.15 
                 1.68 
                 CXCR4 
                 JM 3100 
               
               
                   
                 4 (CXC-R4) ( 
               
               
                 Ssc.6570.1.S1_at 
                 Delta-aminolevulinic acid 
                 3.71 
                 −3.43 
                 −3.05 
                 −1.66 
                 ALAD 
                 delta-aminolevulinic acid 
               
               
                   
                 dehydratase] 
               
               
                 Ssc.17485.1.S1_at 
                 Guanylate cyclase soluble, 
                 3.57 
                 −38.82 
                 −1.77 
                 −7.04 
                 GUCY1A2 
                 nitroglycerin, isosorbide-5- 
               
               
                   
                 alpha-2 chain 
                   
                   
                   
                   
                   
                 mononitrate, isosorbide 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dinitrate, nitroprusside, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isosorbide 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dinitrate/hydralazine 
               
               
                 Ssc.26200.1.S1_at 
                 Thyroid hormone receptor beta-1 
                 3.49 
                 −1.56 
                 7.96 
                 2.52 
                 THRB 
                 3,5-diiodothyropropionic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amiodarone, thyroxine, L- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 triiodothyronine 
               
               
                 Ssc.9595.1.S1_at 
                 Beta platelet-derived growth 
                 3.48 
                 −3.60 
                 1.40 
                 1.65 
                 PDGFRB 
                 dasatinib, sunitinib, 
               
               
                   
                 factor receptor 
                   
                   
                   
                   
                   
                 axitinib, KRN-951, imatinib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 sorafenib, becaplermin 
               
               
                 Ssc.108.1.S1_at 
                 Oxytocin receptor (OT-R) 
                 3.44 
                 −8.53 
                 −16.69 
                 −4.47 
                 OXTR 
                 TT-235 
               
               
                 Ssc.15801.1.A1_at 
                 Protein kinase C, beta 
                 3.36 
                 6.36 
                 3.53 
                 −4.98 
                 PRKCB1 
                 enzastaurin, ruboxistaurin 
               
               
                 Ssc.27928.1.S1_at 
                 Opioid growth factor receptor 
                 3.34 
                 −3.33 
                 −2.89 
                 −3.51 
                 OGFR 
                 enkephalin, methionine 
               
               
                   
                 (OGFr) 
               
               
                 Ssc.12791.1.A1_at 
                 3-hydroxy-3-methylglutaryl- 
                 3.27 
                 2.77 
                 1.77 
                 −2.56 
                 HMGCR 
                 aspirin/pravastatin, 
               
               
                   
                 coenzyme A reductase (HMG-CoA 
                   
                   
                   
                   
                   
                 lovastatin/niacin, 
               
               
                   
                 reductase 
                   
                   
                   
                   
                   
                 ezetimibe/simvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/atorvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fluvastatin, cerivastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 atorvastatin, pravastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 simvastatin, lovastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 rosuvastatin 
               
               
                 Ssc.7933.1.A1_at 
                 Cell division protein kinase 8 
                 3.26 
                 −1.63 
                 −1.78 
                 −3.05 
                 CDK8 
                 flavopiridol 
               
               
                 Ssc.11147.1.S1_at 
                 Aldehyde dehydrogenase, 
                 3.18 
                 1.13 
                 2.00 
                 −1.68 
                 ALDH2 
                 disulfiram, chlorpropamide 
               
               
                   
                 mitochondrial (ALDH class 2) 
               
               
                   
                 (ALDHI) (ALDH-E2) 
               
               
                 Ssc.19608.1.S1_at 
                 Retinoic acid receptor RXR- 
                 3.15 
                 −1.39 
                 −1.73 
                 −3.97 
                 RXRG 
                 bexarotene, retinoic acid, 9- 
               
               
                   
                 gamma 
                   
                   
                   
                   
                   
                 cis-retinoic acid 
               
               
                 Ssc.29260.1.A1_at 
                 Granulocyte colony stimulating 
                 3.15 
                 −2.50 
                 −4.36 
                 −4.68 
                 CSF3R 
                 pegfilgrastim, filgrastim 
               
               
                   
                 factor receptor (G-CSF-R) 
               
               
                   
                 (CD114 antigen)] 
               
               
                 Ssc.22797.1.S1_at 
                 DNA topoisomerase II, beta 
                 3.15 
                 −1.87 
                 1.02 
                 −2.91 
                 TOP2B 
                 novobiocin, etoposide, CPI- 
               
               
                   
                 isozyme 
                   
                   
                   
                   
                   
                 0004Na, pixantrone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 becatecarin, elsamitrucin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 AQ4N, BN 80927, tafluposide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 mitoxantrone, norfloxacin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dexrazoxane, tirapazamine, TAS- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 103, XK469, gatifloxacin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 valrubicin, gemifloxacin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 moxifloxacin, nemorubicin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nalidixic acid, epirubicin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 doxorubicin, daunorubicin 
               
               
                 Ssc.16121.1.A1_at 
                 Corticotropin releasing factor 
                 3.03 
                 −4.50 
                 −17.00 
                 −4.36 
                 CRHR1 
                 Crh, CRA0165, CRA1001, 
               
               
                   
                 receptor 1 
                   
                   
                   
                   
                   
                 SSR125543A 
               
               
                 Ssc.12630.1.A1_at 
                 Sodium/potassium-transporting 
                 2.97 
                 2.81 
                 −7.30 
                 −2.03 
                 ATP1A1 
                 digoxin, omeprazole, 
               
               
                   
                 ATPase alpha-1 chain 
                   
                   
                   
                   
                   
                 ethacrynic acid, perphenazine 
               
               
                 Ssc.13254.1.A1_at 
                 Metabotropic glutamate 
                 2.95 
                 −15.40 
                 −9.66 
                 −3.57 
                 GRM8 
                 fasoracetam 
               
               
                   
                 receptor 8 
               
               
                 Ssc.30888.1.S1_at 
                 Voltage-dependent L-type 
                 2.92 
                 −2.72 
                 1.90 
                 −7.82 
                 CACNA1D 
                 MEM-1003, mibefradil, 
               
               
                   
                 calcium channel alpha-1D 
                   
                   
                   
                   
                   
                 bepridil, nisoldipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isradipine, nicardipine 
               
               
                 Ssc.9565.1.S1_at 
                 Interferon-gamma receptor 
                 2.92 
                 1.63 
                 1.41 
                 −1.23 
                 IFNGR1 
                 interferon gamma-1b 
               
               
                   
                 alpha 
               
               
                 Ssc.15880.1.S1_at 
                 Cysteinyl leukotriene receptor 
                 2.86 
                 1.14 
                 −2.12 
                 −3.42 
                 CYSLTR2 
                 montelukast, zafirlukast 
               
               
                   
                 2 (CysLTR2) 
               
               
                 Ssc.2753.1.S1_at 
                 Serine/threonine-protein 
                 2.77 
                 −4.42 
                 −7.50 
                 −4.52 
                 PLK1 
                 BI 2536 
               
               
                   
                 kinase PLK1 
               
               
                 Ssc.16123.1.A1_at 
                 cAMP-specific 3′,5′-cyclic 
                 2.75 
                 −3.97 
                 −3.49 
                 −1.46 
                 PDE4A 
                 arofylline, tetomilast, L 
               
               
                   
                 phosphodiesterase 4A 
                   
                   
                   
                   
                   
                 869298, anagrelide, cilomilast, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 milrinone, rolipram, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amrinone, roflumilast, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline, caffeine 
               
               
                 Ssc.11383.1.A1_at 
                 Glutamate receptor 3 
                 2.61 
                 1.85 
                 −1.87 
                 −2.43 
                 GRIA3 
                 talampanel, Org 24448, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 LY451395, tezampanel 
               
               
                 Ssc.14403.1.S1_at 
                 Sodium/potassium-transporting 
                 2.61 
                 −1.95 
                 −8.51 
                 −6.43 
                 ATP1A2 
                 digoxin, omeprazole, 
               
               
                   
                 ATPase alpha-2 chain 
                   
                   
                   
                   
                   
                 ethacrynic acid, perphenazine 
               
               
                 Ssc.21754.1.A1_at 
                 Collagen alpha 1(VI) chain 
                 2.57 
                 −47.00 
                 −5.79 
                 −4.37 
                 COL6A1 
                 collagenase 
               
               
                 Ssc.6498.1.A1_at 
                 Mitogen-activated protein 
                 2.41 
                 −10.79 
                 −5.78 
                 −3.26 
                 MAPK12 
                 SCIO-469 
               
               
                   
                 kinase 12 (Mitogen-activated 
               
               
                   
                 protein kinase p38 gamma) 
               
               
                 Ssc.16167.1.S1_at 
                 Rho-associated protein kinase 1 
                 2.40 
                 2.32 
                 2.83 
                 3.00 
                 ROCK1 
                 fasudil, Y-27632 
               
               
                 Ssc.12781.1.A1_at 
                 Toll-like receptor 4 
                 2.39 
                 1.83 
                 −1.52 
                 −6.10 
                 TLR4 
                 TAK-242 
               
               
                 Ssc.29366.1.A1_at 
                 DNA topoisomerase I 
                 2.37 
                 −2.30 
                 −2.87 
                 −10.72 
                 TOP1 
                 elsamitrucin, T 0128, CT-2106, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 BN 80927, tafluposide, TAS-103, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 beta-lapachone, irinotecan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 topotecan, 9-amino-20- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 camptothecin, rubitecan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 gimatecan, karenitecin 
               
               
                 Ssc.14485.1.S1_at 
                 Parathyroid 
                 2.28 
                 −1.62 
                 −3.40 
                 −6.83 
                 PTHR1 
                 teriparatide 
               
               
                   
                 hormone/parathyroid hormone- 
               
               
                   
                 related peptide receptor 
               
               
                 Ssc.12238.1.A1_at 
                 Cysteinyl leukotriene receptor 
                 2.28 
                 −1.73 
                 −1.34 
                 −6.96 
                 CYSLTR1 
                 zeneca ZD 3523, montelukast, 
               
               
                   
                 1 (CysLTR1) 
                   
                   
                   
                   
                   
                 zafirlukast 
               
               
                 Ssc.3607.1.S1_at 
                 Interferon-alpha/beta receptor 
                 2.28 
                 4.65 
                 1.11 
                 −1.56 
                 IFNAR2 
                 interferon beta-1a, interferon 
               
               
                   
                 beta chain 
                   
                   
                   
                   
                   
                 alfa-2b, interferon alfacon-1, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 PEG-interferon alfa-2a, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a/ribavirin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegintron, interferon beta-1b, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 IFNA2A 
               
               
                 Ssc.2548.1.S1_at 
                 DNA polymerase epsilon p17] 
                 2.27 
                 1.93 
                 −1.67 
                 −1.21 
                 POLE3 
                 gemcitabine 
               
               
                 Ssc.19706.1.A1_at 
                 Mitogen-activated protein 
                 2.25 
                 −4.27 
                 −2.31 
                 −4.98 
                 MAPK8 
                 aplidine 
               
               
                   
                 kinase 8 
               
               
                 Ssc.15382.1.S1_at 
                 Cannabinoid receptor 2 (CB2) 
                 2.22 
                 3.48 
                 −1.37 
                 −4.69 
                 CNR2 
                 BAY 38-7271, delta-9- 
               
               
                   
                 (CB-2) (CX5) 
                   
                   
                   
                   
                   
                 tetrahydrocannabinol 
               
               
                 Ssc.4756.1.A1_at 
                 Adenosine A3 receptor 
                 2.15 
                 2.10 
                 1.88 
                 −1.81 
                 ADORA3 
                 adenosine, dyphylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aminophylline, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, caffeine 
               
               
                 Ssc.23261.1.A1_at 
                 Trifunctional purine 
                 2.15 
                 −3.54 
                 −3.66 
                 −5.67 
                 GART 
                 LY231514 
               
               
                   
                 biosynthetic protein 
               
               
                   
                 adenosine-3 
               
               
                 Ssc.27293.1.A1_at 
                 Hypoxanthine-guanine 
                 2.15 
                 −1.16 
                 1.63 
                 −7.14 
                 HPRT1 
                 6-mercaptopurine, thioguanine, 
               
               
                   
                 phosphoribosyltransferase 
                   
                   
                   
                   
                   
                 azathioprine 
               
               
                 Ssc.14476.1.S1_at 
                 Interleukin-2 receptor alpha 
                 2.07 
                 −8.52 
                 −8.73 
                 −5.00 
                 IL2RA 
                 LMB-2, daclizumab, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 basiliximab, aldesleukin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 denileukin diftitox 
               
               
                 Ssc.27232.1.S1_at 
                 Succinate semialdehyde 
                 2.06 
                 1.12 
                 −2.84 
                 −5.73 
                 ALDH5A1 
                 valproic acid 
               
               
                   
                 dehydrogenase, mitochondrial 
               
               
                 Ssc.10142.1.A1_at 
                 Dihydropyrimidine 
                 2.06 
                 2.17 
                 1.13 
                 −2.68 
                 DPYD 
                 eniluracil 
               
               
                   
                 dehydrogenase [NADP+] 
               
               
                 Ssc.1908.1.S1_at 
                 FKBP-rapamycin associated 
                 1.99 
                 1.13 
                 −1.88 
                 −1.46 
                 FRAP1 
                 AP23573, temsirolimus, 
               
               
                   
                 protein (FRAP) 
                   
                   
                   
                   
                   
                 tacrolimus, everolimus 
               
               
                 Ssc.204.1.S1_at 
                 Cytochrome P450 3A4 
                 1.97 
                 −3.35 
                 2.16 
                 −1.42 
                 CYP3A4 
                 ketoconazole 
               
               
                 Ssc.18459.1.S1_at 
                 Amiloride-sensitive sodium 
                 1.97 
                 −2.41 
                 1.43 
                 −1.93 
                 SCNN1A 
                 triamterene/hydrochlorothiazide, 
               
               
                   
                 channel alpha- 
                   
                   
                   
                   
                   
                 amiloride, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amiloride/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 triamterene 
               
               
                 Ssc.24889.1.S1_at 
                 Arachidonate 12-lipoxygenase, 
                 1.97 
                 2.83 
                 −1.18 
                 −2.78 
                 ALOX12 
                 sulfasalazine, balsalazide, 5- 
               
               
                   
                 12S-type 
                   
                   
                   
                   
                   
                 aminosalicylic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 masoprocol, verteporfin 
               
               
                 Ssc.15748.2.S2_at 
                 T lymphocyte activation 
                 1.95 
                 −1.24 
                 1.54 
                 −3.12 
                 CD80 
                 abatacept 
               
               
                   
                 antigen CD80 
               
               
                 Ssc.5826.1.A1_at 
                 Macrophage colony stimulating 
                 1.93 
                 −4.97 
                 −13.18 
                 1.61 
                 CSF1R 
                 sunitinib 
               
               
                   
                 factor I receptor (CD115 
               
               
                   
                 antigen) 
               
               
                 Ssc.15822.1.S1_at 
                 Coagulation factor V 
                 1.92 
                 3.76 
                 1.89 
                 −1.75 
                 F5 
                 drotrecogin alfa 
               
               
                 Ssc.9262.1.A1_at 
                 Histamine H1 receptor 
                 1.91 
                 −4.10 
                 −3.91 
                 −1.86 
                 HRH1 
                 nitisinone 
               
               
                 Ssc.62.2.S1_a_at 
                 Interleukin-6 (IL-6) ( 
                 1.89 
                 −6.32 
                 2.77 
                 −1.04 
                 IL6 
                 tocilizumab 
               
               
                 Ssc.14258.1.S1_at 
                 Amyloid beta A4 protein 
                 1.87 
                 3.33 
                 1.34 
                 −1.02 
                 APP 
                 AAB-001 
               
               
                 Ssc.15878.1.S1_at 
                 Serine/threonine protein 
                 1.85 
                 3.22 
                 3.62 
                 −1.49 
                 PPP3CA 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 phosphatase 2B 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                 Ssc.19379.1.A1_at 
                 Voltage-dependent L-type 
                 1.83 
                 −1.34 
                 1.07 
                 −3.27 
                 CACNA1C 
                 clevidipine, MEM-1003, 
               
               
                   
                 calcium channel alpha-1C 
                   
                   
                   
                   
                   
                 amlodipine/olmesartan 
               
               
                   
                 subunit 
                   
                   
                   
                   
                   
                 medoxomil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/benazepril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 diltiazem, verapamil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 mibefradil, bepridil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalapril/felodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/atorvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nisoldipine, isradipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 felodipine, nimodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nitrendipine, amlodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nicardipine, nifedipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trandolapril/verapamil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 diltiazem/enalapril 
               
               
                 Ssc.10215.1.A1_at 
                 High-affinity cAMP-specific 
                 1.83 
                 1.12 
                 −8.48 
                 −15.51 
                 PDE8A 
                 dyphylline, nitroglycerin, 
               
               
                   
                 and IBMX-insensitive 3′,5′- 
                   
                   
                   
                   
                   
                 aminophylline, anagrelide, 
               
               
                   
                 cyclic phosphodiesterase 8A 
                   
                   
                   
                   
                   
                 milrinone, dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tolbutamide, theophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline 
               
               
                 Ssc.20944.1.S1_at 
                 Carbonic anhydrase XIV 
                 1.82 
                 −3.49 
                 −5.34 
                 −12.64 
                 CA14 
                 methazolamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 acetazolamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trichloromethiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 chlorothiazide, chlorthalidone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benzthiazide, sulfacetamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 topiramate 
               
               
                 Ssc.4125.1.A1_at 
                 Histone deacetylase 5 (HD5) 
                 1.82 
                 −4.64 
                 −4.18 
                 −2.74 
                 HDAC5 
                 tributyrin, PXD101, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pyroxamide, vorinostat, FR 
               
               
                   
                   
                   
                   
                   
                   
                   
                 901228 
               
               
                 Ssc.9272.1.S1_at 
                 Tumor-associated calcium 
                 1.81 
                 3.94 
                 176.50 
                 2.07 
                 TACSTD1 
                 tucotuzumab celmoleukin 
               
               
                   
                 signal transducer 1 (EPCAM 
               
               
                   
                 antigen) 
               
               
                 Ssc.6301.1.S1_at 
                 Aromatic-L-amino-acid 
                 1.76 
                 1.80 
                 −4.91 
                 −1.88 
                 DDC 
                 carbidopa/entacapone/levodopa, 
               
               
                   
                 decarboxylase 
                   
                   
                   
                   
                   
                 carbidopa/levodopa, S(−)- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 carbidopa, L-dopa 
               
               
                 Ssc.15995.1.S1_at 
                 Potassium voltage-gated 
                 1.74 
                 −26.30 
                 −13.45 
                 −2.79 
                 KCNE1 
                 nicorandil, amiodarone, 
               
               
                   
                 channel subfamily E member 1 
                   
                   
                   
                   
                   
                 azimilide 
               
               
                 Ssc.7581.1.A1_at 
                 FL cytokine receptor precursor 
                 1.69 
                 1.04 
                 −1.81 
                 1.01 
                 FLT3 
                 CHIR-258, sorafenib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lestaurtinib, CGP 41251 
               
               
                 Ssc.26325.1.S1_at 
                 Cystic fibrosis transmembrane 
                 1.60 
                 −5.71 
                 4.77 
                 −8.99 
                 CFTR 
                 SP 303 
               
               
                   
                 conductance regulator (CFTR) 
               
               
                 Ssc.19691.1.S1_at 
                 Platelet-activating factor 
                 1.59 
                 1.16 
                 3.01 
                 1.47 
                 PLA2G7 
                 darapladib 
               
               
                   
                 acetylhydrolase 
               
               
                 Ssc.24714.1.A1_at 
                 Excitatory amino acid 
                 1.58 
                 −2.29 
                 −7.61 
                 −3.45 
                 SLC1A2 
                 riluzole 
               
               
                   
                 transporter 2 (Sodium- 
               
               
                   
                 dependent glutamate/aspartate 
               
               
                   
                 transporter 2) 
               
               
                 Ssc.22477.1.S1_at 
                 Collagen alpha 1(IV) chain 
                 1.58 
                 −5.08 
                 −1.78 
                 1.04 
                 COL4A1 
                 collagenase 
               
               
                 Ssc.227.1.S1_at 
                 Potassium-transporting ATPase 
                 1.56 
                 −5.89 
                 −51.53 
                 −15.60 
                 ATP4B 
                 ilaprazole, TAK-390MR, 
               
               
                   
                 beta 
                   
                   
                   
                   
                   
                 tenatoprazole, AGN 201904, AR- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 H047108, esomeprazole 
               
               
                   
                   
                   
                   
                   
                   
                   
                 magnesium, omeprazole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lansoprazole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amoxicillin/clarithromycin/ 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lansoprazole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 rabeprazole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pantoprazole 
               
               
                 Ssc.30147.1.A1_at 
                 Fibroblast growth factor 
                 1.56 
                 1.13 
                 −1.05 
                 −1.18 
                 FGFR2 
                 palifermin 
               
               
                   
                 receptor 2 
               
               
                 Ssc.9523.1.A1_at 
                 Methylated-DNA--protein- 
                 1.55 
                 −1.17 
                 3.35 
                 1.47 
                 MGMT 
                 O6-benzylguanine 
               
               
                   
                 cysteine methyltransferase 
               
               
                 Ssc.26466.1.A1_at 
                 Integrin beta-3 (CD61 antigen 
                 1.55 
                 −1.49 
                 −4.11 
                 −2.73 
                 ITGB3 
                 TP 9201, EMD121974, tirofiban 
               
               
                 Ssc.5592.1.S1_at 
                 Protein 
                 1.49 
                 −3.49 
                 −2.81 
                 −3.68 
                 FNTA 
                 lonafarnib, tipifarnib 
               
               
                   
                 farnesyltransferase/ 
               
               
                   
                 geranylgeranyltransferase 
               
               
                   
                 type I alpha 
               
               
                 Ssc.17986.1.A1_at 
                 Poly [ADP-ribose] polymerase-1 
                 1.47 
                 −6.14 
                 −4.64 
                 −5.80 
                 PARP1 
                 INO-1001 
               
               
                 Ssc.11051.1.S1_at 
                 Cell division protein kinase 4 
                 1.44 
                 −7.67 
                 −4.96 
                 23.75 
                 CDK4 
                 PD-0332991, flavopiridol 
               
               
                 Ssc.20818.1.S1_at 
                 Interleukin-2 receptor beta 
                 1.43 
                 6.35 
                 −1.17 
                 −5.23 
                 IL2RB 
                 humanized MiK-Beta-1, 
               
               
                   
                 chain 
                   
                   
                   
                   
                   
                 aldesleukin, denileukin 
               
               
                   
                   
                   
                   
                   
                   
                   
                 diftitox 
               
               
                 Ssc.16489.1.S1_at 
                 Interleukin-7 receptor alpha 
                 1.42 
                 2.34 
                 1.86 
                 −6.31 
                 IL7R 
                 recombinant human interleukin-7 
               
               
                   
                 chain 
               
               
                 Ssc.10287.1.A1_at 
                 Transforming growth factor 
                 1.41 
                 −4.54 
                 1.43 
                 1.67 
                 TGFB2 
                 AP-12009 
               
               
                   
                 beta 2 
               
               
                 Ssc.14375.1.A1_at 
                 ribonucleotide reductase M2 B 
                 1.40 
                 −2.19 
                 −5.17 
                 −2.28 
                 RRM2B 
                 triapine, hydroxyurea 
               
               
                 Ssc.16823.1.S1_at 
                 P2Y purinoceptor 12 (P2Y12) 
                 1.38 
                 1.19 
                 1.41 
                 1.11 
                 P2RY12 
                 prasugrel, AZD 6140 
               
               
                   
                 (P2Y12 platelet ADP receptor) 
                   
                   
                   
                   
                   
                 (Ticagrelor), clopidogrel 
               
               
                   
                 (P2Y(ADP)) 
               
               
                 Ssc.11164.1.A1_at 
                 DNA polymerase gamma subunit 1 
                 1.37 
                 −1.33 
                 −3.67 
                 −3.60 
                 POLG 
                 stavudine, vidarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 zalcitabine 
               
               
                 Ssc.10219.1.A1_at 
                 Excitatory amino acid 
                 1.36 
                 1.24 
                 −3.38 
                 −1.03 
                 SLC1A6 
                 riluzole 
               
               
                   
                 transporter 4 
               
               
                 Ssc.3815.1.S1_at 
                 RAC-beta serine/threonine- 
                 1.35 
                 −3.13 
                 −3.28 
                 −3.19 
                 AKT2 
                 enzastaurin 
               
               
                   
                 protein kinase 
               
               
                 Ssc.19619.1.S1_at 
                 Proto-oncogene tyrosine- 
                 1.35 
                 −1.51 
                 −3.32 
                 −2.41 
                 LCK 
                 dasatinib 
               
               
                   
                 protein kinase LCK 
               
               
                 Ssc.2926.1.S1_at 
                 Heme oxygenase 2 
                 1.34 
                 −1.43 
                 −4.13 
                 −1.81 
                 HMOX2 
                 tin mesoporphyrin 
               
               
                 Ssc.11171.1.S1_at 
                 Adenosine deaminase 
                 1.32 
                 −2.04 
                 −3.23 
                 1.12 
                 ADA 
                 pentostatin, vidarabine 
               
               
                 Ssc.16621.1.A1_at 
                 Excitatory amino acid 
                 1.27 
                 −7.18 
                 −3.04 
                 −8.29 
                 SLC1A1 
                 riluzole 
               
               
                   
                 transporter 3 
               
               
                 Ssc.11549.1.A1_at 
                 Dual specificity mitogen- 
                 1.25 
                 −33.67 
                 −11.33 
                 −6.48 
                 MAP2K1 
                 PD 0325901 
               
               
                   
                 activated protein kinase 
               
               
                   
                 kinase 1 
               
               
                 Ssc.6356.1.S1_at 
                 Ornithine decarboxylase 
                 1.24 
                 −1.36 
                 −1.74 
                 −1.84 
                 ODC1 
                 tazarotene, eflornithine 
               
               
                 Ssc.15999.1.A1_at 
                 Vascular endothelial growth 
                 1.24 
                 1.24 
                 18.52 
                 −11.02 
                 KDR 
                 AEE 788, sunitinib, AZD 2171, 
               
               
                   
                 factor receptor 2 (VEGFR-2) 
                   
                   
                   
                   
                   
                 pazopanib, XL647, CEP 7055, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 BMS-582664, KRN-951, vatalanib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 sorafenib, vandetanib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegaptanib 
               
               
                 Ssc.9669.1.S1_at 
                 Cell division protein kinase 5 
                 1.21 
                 −2.68 
                 −17.06 
                 −1.65 
                 CDK5 
                 flavopiridol 
               
               
                 Ssc.115.1.S1_s_at 
                 Heme oxygenase 1 
                 1.18 
                 −2.09 
                 −3.40 
                 −3.55 
                 HMOX1 
                 tin mesoporphyrin 
               
               
                 Ssc.17224.1.S1_at 
                 Toll-like receptor 8 
                 1.17 
                 6.49 
                 3.13 
                 −1.52 
                 TLR8 
                 resiquimod 
               
               
                 Ssc.8046.1.A1_at 
                 peptidylprolyl isomerase A 
                 1.16 
                 −1.08 
                 1.39 
                 1.26 
                 PPIA 
                 N-methyl-4-Ile-cyclosporin 
               
               
                   
                 isoform 1 
               
               
                 Ssc.7297.1.S1_at 
                 Amine oxidase [flavin- 
                 1.16 
                 6.42 
                 7.02 
                 −1.13 
                 MAOB 
                 safinamide, ladostigil, 
               
               
                   
                 containing] B (MAO-B) 
                   
                   
                   
                   
                   
                 rasagiline, selegiline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dextroamphetamine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 procainamide, tranylcypromine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 phenelzine, isocarboxazid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benzphetamine 
               
               
                 Ssc.28329.1.S1_at 
                 DNA polymerase beta 
                 1.14 
                 1.19 
                 1.07 
                 5.25 
                 POLB 
                 nelarabine, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 stavudine, trifluridine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vidarabine, zalcitabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 entecavir 
               
               
                 Ssc.12202.2.S1_at 
                 Farnesyl pyrophosphate 
                 1.12 
                 −1.26 
                 −2.68 
                 −1.13 
                 FDPS 
                 YM 529, alendronic acid, 
               
               
                   
                 synthetase 
                   
                   
                   
                   
                   
                 pamidronic acid 
               
               
                 Ssc.19700.1.S1_at 
                 Serine/threonine protein 
                 1.11 
                 1.13 
                 1.34 
                 1.09 
                 PPP3CB 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 phosphatase 2B catalytic 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                   
                 subunit, beta 
               
               
                 Ssc.8549.1.A1_at 
                 Guanylate cyclase soluble, 
                 1.11 
                 1.84 
                 −2.00 
                 −2.59 
                 GUCY1A3 
                 nitroglycerin, isosorbide-5- 
               
               
                   
                 alpha-3 chain 
                   
                   
                   
                   
                   
                 mononitrate, isosorbide 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dinitrate, nitroprusside, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isosorbide 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dinitrate/hydralazine 
               
               
                 Ssc.15374.1.S1_at 
                 COL14A1 protein 
                 1.10 
                 −17.71 
                 3.79 
                 2.24 
                 COL14A1 
                 collagenase 
               
               
                 Ssc.15901.1.S1_at 
                 cGMP-inhibited 3′,5′-cyclic 
                 1.10 
                 −13.33 
                 −3.16 
                 −1.41 
                 PDE3A 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase A 
                   
                   
                   
                   
                   
                 medorinone, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cilostazol, dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amrinone, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline 
               
               
                 Ssc.16000.1.A1_at 
                 Vascular endothelial growth 
                 1.08 
                 −3.40 
                 3.34 
                 1.72 
                 FLT1 
                 sunitinib, axitinib, CEP 7055 
               
               
                   
                 factor receptor 1 
               
               
                 Ssc.20987.1.S1_at 
                 Thrombopoietin receptor] 
                 1.06 
                 −1.58 
                 −3.97 
                 −5.87 
                 MPL 
                 SB-497115 
               
               
                 Ssc.11149.1.S1_at 
                 Carbonic anhydrase IX 
                 1.04 
                 −1.91 
                 −1.33 
                 −1.26 
                 CA9 
                 cG250, I 131 chimeric G250, Y 
               
               
                   
                   
                   
                   
                   
                   
                   
                 90 chimeric G250, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 methazolamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 acetazolamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trichloromethiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 chlorothiazide, chlorthalidone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benzthiazide, sulfacetamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 topiramate 
               
               
                 Ssc.8726.1.A1_at 
                 Amidophosphoribosyltransferase 
                 1.03 
                 1.24 
                 4.16 
                 −1.11 
                 PPAT 
                 6-mercaptopurine, thioguanine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 azathioprine 
               
               
                 Ssc.11406.1.A1_a_at 
                 Interleukin-1 receptor, type I 
                 1.03 
                 2.70 
                 −2.44 
                 1.42 
                 IL1R1 
                 anakinra 
               
               
                 Ssc.14506.1.S1_at 
                 DNA topoisomerase II, alpha 
                 1.01 
                 3.80 
                 −1.18 
                 −14.30 
                 TOP2A 
                 novobiocin, etoposide, CPI- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 0004Na, pixantrone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 becatecarin, elsamitrucin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 AQ4N, BN 80927, tafluposide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 mitoxantrone, norfloxacin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dexrazoxane, tirapazamine, TAS- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 103, gatifloxacin, valrubicin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 gemifloxacin, moxifloxacin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nemorubicin, nalidixic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 epirubicin, doxorubicin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 daunorubicin 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Day 21 prescription. 
               
             
          
           
               
                   
                   
                 Fold 
                 Fold 
                 Fold 
                 Fold 
                   
                   
               
               
                   
                   
                 Change 
                 Change 
                 Change 
                 Change 
               
               
                   
                   
                 D 7/ 
                 D 21/ 
                 D 60/ 
                 D 180/ 
                 Gene 
               
               
                 Probe ID 
                 Name 
                 Base 
                 Base 
                 Base 
                 Base 
                 Symbol 
                 Drugs 
               
               
                   
               
             
          
           
               
                 Ssc.23793.1.S1_at 
                 T-cell surface antigen CD2 
                 −3.27 
                 79.25 
                 93.34 
                 5.20 
                 CD2 
                 alefacept, siplizumab 
               
               
                 SscAffx.20.1.S1_at 
                 T-cell surface glycoprotein 
                 −2.19 
                 14.07 
                 10.96 
                 3.62 
                 CD3G 
                 visilizumab, MT103 
               
               
                   
                 CD3 gamma chain 
               
               
                 Ssc.19532.1.S1_at 
                 Guanylate cyclase soluble, 
                 −4.28 
                 12.74 
                 3.04 
                 2.13 
                 GUCY1B3 
                 nitroglycerin, isosorbide-5- 
               
               
                   
                 beta-1 chain 
                   
                   
                   
                   
                   
                 mononitrate, isosorbide 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dinitrate, nitroprusside, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isosorbide 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dinitrate/hydralazine 
               
               
                 Ssc.7176.1.A1_at 
                 C-X-C chemokine receptor type 
                 3.74 
                 10.91 
                 8.15 
                 1.68 
                 CXCR4 
                 JM 3100 
               
               
                   
                 4 (CXC-R4) (CXCR-4) (CD184 
               
               
                   
                 antigen). 
               
               
                 Ssc.2714.1.S1_a_at 
                 Proto-oncogene tyrosine- 
                 −4.26 
                 9.56 
                 12.54 
                 3.93 
                 FYN 
                 dasatinib 
               
               
                   
                 protein kinase FYN 
               
               
                 Ssc.15739.1.S1_at 
                 Cytokine receptor common gamma 
                 −1.12 
                 9.42 
                 1.90 
                 −1.28 
                 IL2RG 
                 aldesleukin, denileukin 
               
               
                   
                 chain (Interleukin- 2 
                   
                   
                   
                   
                   
                 diftitox 
               
               
                   
                 receptor gamma chain) (IL-2R 
               
               
                   
                 gamma chain) (CD132 antigen). 
               
               
                 Ssc.11381.1.S1_at 
                 Interferon-alpha/beta receptor 
                 10.45 
                 8.08 
                 2.61 
                 −1.30 
                 IFNAR1 
                 interferon beta-1a, interferon 
               
               
                   
                 alpha chain 
                   
                   
                   
                   
                   
                 alfa-2b, interferon alfacon-1, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 PEG-interferon alfa-2a, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a/ribavirin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegintron, interferon beta-1b, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 IFNA2A 
               
               
                 Ssc.10256.1.A1_at 
                 cAMP-specific 3′,5′-cyclic 
                 −1.89 
                 6.74 
                 2.20 
                 2.44 
                 PDE4B 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase 4B 
                   
                   
                   
                   
                   
                 arofylline, tetomilast, L 
               
               
                   
                   
                   
                   
                   
                   
                   
                 869298, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 anagrelide, cilomilast, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 milrinone, rolipram, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 caffeine 
               
               
                 Ssc.17224.1.S1_at 
                 Toll-like receptor 8 
                 1.17 
                 6.49 
                 3.13 
                 −1.52 
                 TLR8 
                 resiquimod 
               
               
                 Ssc.7297.1.S1_at 
                 Amine oxidase [flavin- 
                 1.16 
                 6.42 
                 7.02 
                 −1.13 
                 MAOB 
                 safinamide, ladostigil, 
               
               
                   
                 containing] B (Monoamine 
                   
                   
                   
                   
                   
                 rasagiline, selegiline, 
               
               
                   
                 oxidase) (MAO-B). 
                   
                   
                   
                   
                   
                 dextroamphetamine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 procainamide, tranylcypromine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 phenelzine, isocarboxazid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benzphetamine 
               
               
                 Ssc.15801.1.A1_at 
                 Protein kinase C, beta 
                 3.36 
                 6.36 
                 3.53 
                 −4.98 
                 PRKCB1 
                 enzastaurin, ruboxistaurin 
               
               
                 Ssc.20818.1.S1_at 
                 Interleukin-2 receptor beta 
                 1.43 
                 6.35 
                 −1.17 
                 −5.23 
                 IL2RB 
                 humanized MiK-Beta-1, 
               
               
                   
                 chain (IL-2 receptor) 
                   
                   
                   
                   
                   
                 aldesleukin, denileukin 
               
               
                   
                   
                   
                   
                   
                   
                   
                 diftitox 
               
               
                 Ssc.12937.1.S1_at 
                 Presenilin 1 (PS-1) (S182 
                 −14.09 
                 6.21 
                 2.48 
                 3.79 
                 PSEN1 
                 (R)-flurbiprofen 
               
               
                   
                 protein). 
               
               
                 Ssc.15932.1.S1_at 
                 Integrin alpha-V 
                 −6.15 
                 5.79 
                 2.94 
                 3.14 
                 ITGAV 
                 abciximab, CNTO 95, EMD121974 
               
               
                 Ssc.26328.1.S1_at 
                 C-C chemokine receptor type 5 
                 −2.53 
                 5.61 
                 3.25 
                 1.29 
                 CCR5 
                 maraviroc, vicriviroc, SCH 
               
               
                   
                 (CCR5) (CD195 antigen). 
                   
                   
                   
                   
                   
                 351125 
               
               
                 Ssc.12845.1.S1_at 
                 Cell division protein kinase 6 
                 −6.56 
                 5.40 
                 4.77 
                 5.13 
                 CDK6 
                 PD-0332991, flavopiridol 
               
               
                 Ssc.17155.1.A1_at 
                 heparanase; heparanase-1 
                 4.81 
                 5.38 
                 2.98 
                 −1.83 
                 HPSE 
                 heparanase inhibitor PI-88 
               
               
                 Ssc.13460.1.A1_at 
                 Histone deacetylase 9 (HD9) 
                 −6.40 
                 5.13 
                 −1.79 
                 5.72 
                 HDAC9 
                 tributyrin, PXD101, 
               
               
                   
                 (HD7B) (HD7) 
                   
                   
                   
                   
                   
                 pyroxamide, vorinostat, FR 
               
               
                   
                   
                   
                   
                   
                   
                   
                 901228 
               
               
                 Ssc.24528.1.S1_at 
                 Angiotensin-converting enzyme 
                 −1.61 
                 5.01 
                 2.33 
                 4.76 
                 ACE 
                 pentopril, perindoprilat, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/benazepril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lisinopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benazepril, enalapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 perindopril, captopril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalapril/felodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/moexipril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benazepril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/quinapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fosinopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 captopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalapril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 ramipril, moexipril, quinapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lisinopril, enalaprilat, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trandolapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trandolapril/verapamil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 diltiazem/enalapril, fosinopril 
               
               
                 Ssc.26351.1.S1_at 
                 cAMP-specific 3′,5′-cyclic 
                 4.67 
                 4.99 
                 3.61 
                 −1.15 
                 PDE4D 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase 4D 
                   
                   
                   
                   
                   
                 arofylline, tetomilast, L 
               
               
                   
                   
                   
                   
                   
                   
                   
                 869298, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 anagrelide, cilomilast, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 milrinone, rolipram, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 caffeine 
               
               
                 Ssc.15601.1.A1_s_at 
                 Interleukin-1 beta precursor 
                 8.18 
                 4.65 
                 −14.71 
                 −2.84 
                 IL1B 
                 IL-1 trap 
               
               
                   
                 (IL-1 beta) 
               
               
                 Ssc.3607.1.S1_at 
                 Interferon-alpha/beta receptor 
                 2.28 
                 4.65 
                 1.11 
                 −1.56 
                 IFNAR2 
                 interferon beta-1a, interferon 
               
               
                   
                 beta chain 
                   
                   
                   
                   
                   
                 alfa-2b, interferon alfacon-1, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 PEG-interferon alfa-2a, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a/ribavirin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegintron, interferon beta-1b, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 IFNA2A 
               
               
                 Ssc.20841.1.S1_at 
                 Proto-oncogene tyrosine- 
                 −1.13 
                 4.37 
                 −2.59 
                 −1.93 
                 SRC 
                 dasatinib, AZM-475271 
               
               
                   
                 protein kinase Src 
               
               
                 Ssc.11200.1.S1_a_at 
                 Proto-oncogene tyrosine- 
                 −1.15 
                 4.28 
                 −3.41 
                 −1.18 
                 ABL1 
                 imatinib, temozolomide 
               
               
                   
                 protein kinase ABL1 
               
               
                 Ssc.22974.1.A1_at 
                 Metabotropic glutamate 
                 −1.05 
                 4.28 
                 −2.05 
                 −5.66 
                 GRM1 
                 fasoracetam 
               
               
                   
                 receptor 1 
               
               
                 Ssc.7111.1.A1_at 
                 Ribonucleoside-diphosphate 
                 −13.13 
                 4.08 
                 1.37 
                 1.67 
                 RRM2 
                 gemcitabine, triapine, 
               
               
                   
                 reductase M2 chain 
                   
                   
                   
                   
                   
                 hydroxyurea, fludarabine 
               
               
                   
                 (Ribonucleotide reductase 
                   
                   
                   
                   
                   
                 phosphate 
               
               
                   
                 small chain) 
               
               
                 Ssc.9272.1.S1_at 
                 Tumor-associated calcium 
                 1.81 
                 3.94 
                 176.50 
                 2.07 
                 TACSTD1 
                 tucotuzumab celmoleukin 
               
               
                   
                 signal transducer 1 (EPCAM 
               
               
                   
                 antigen) 
               
               
                 Ssc.16160.1.S1_at 
                 T lymphocyte activation 
                 −1.55 
                 3.88 
                 −1.37 
                 1.18 
                 CD86 
                 abatacept 
               
               
                   
                 antigen CD86 
               
               
                 Ssc.14506.1.S1_at 
                 DNA topoisomerase II, alpha 
                 1.01 
                 3.80 
                 −1.18 
                 −14.30 
                 TOP2A 
                 novobiocin, etoposide, CPI- 
               
               
                   
                 isozyme 
                   
                   
                   
                   
                   
                 0004Na, pixantrone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 becatecarin, elsamitrucin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 AQ4N, BN 80927, tafluposide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 mitoxantrone, norfloxacin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dexrazoxane, tirapazamine, TAS- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 103, gatifloxacin, valrubicin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 gemifloxacin, moxifloxacin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nemorubicin, nalidixic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 epirubicin, doxorubicin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 daunorubicin 
               
               
                 Ssc.15822.1.S1_at 
                 Coagulation factor V 
                 1.92 
                 3.76 
                 1.89 
                 −1.75 
                 F5 
                 drotrecogin alfa 
               
               
                   
                 (Activated protein C 
               
               
                   
                 cofactor). 
               
               
                 Ssc.9034.1.A1_at 
                 Proteinase activated receptor 
                 −1.29 
                 3.75 
                 −1.40 
                 1.37 
                 F2R 
                 chrysalin, argatroban, 
               
               
                   
                 1 precursor (PAR-1) (Thrombin 
                   
                   
                   
                   
                   
                 bivalirudin 
               
               
                   
                 receptor) 
               
               
                 Ssc.15886.1.S1_at 
                 Apopain precursor (Caspase-3) 
                 −3.02 
                 3.64 
                 2.31 
                 2.29 
                 CASP3 
                 IDN-6556 
               
               
                   
                 (CASP-3) 
               
               
                 Ssc.17518.1.S1_at 
                 Adenosine A1 receptor 
                 −3.16 
                 3.44 
                 −1.56 
                 1.58 
                 ADORA1 
                 adenosine, dyphylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aminophylline, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, caffeine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tecadenoson 
               
               
                 Ssc.14258.1.S1_at 
                 Amyloid beta A4 protein 
                 1.87 
                 3.33 
                 1.34 
                 −1.02 
                 APP 
                 AAB-001 
               
               
                   
                 precursor (APP) (ABPP) 
               
               
                 Ssc.14471.1.S1_at 
                 B-lymphocyte antigen CD19 
                 9.54 
                 3.30 
                 −10.32 
                 3.04 
                 CD19 
                 combotox, HD37-dgRTA, MT103 
               
               
                   
                 precursor (Differentiation 
               
               
                   
                 antigen CD19 
               
               
                 Ssc.15878.1.S1_at 
                 Serine/threonine protein 
                 1.85 
                 3.22 
                 3.62 
                 −1.49 
                 PPP3CA 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 phosphatase 2B catalytic 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                   
                 subunit, alpha 
               
               
                 Ssc.21108.1.S1_at 
                 Complement C5 
                 −17.35 
                 3.21 
                 618.80 
                 9.28 
                 C5 
                 eculizumab 
               
               
                 Ssc.16186.1.S1_at 
                 T-cell surface glycoprotein 
                 9.00 
                 3.12 
                 2.12 
                 −5.66 
                 CD3E 
                 visilizumab, MT103, muromonab- 
               
               
                   
                 CD3 epsilon chain (T-cell 
                   
                   
                   
                   
                   
                 CD3 
               
               
                   
                 surface antigen T3/Leu-4 
               
               
                   
                 epsilon chain) 
               
               
                 Ssc.24966.1.S1_at 
                 Purine nucleoside 
                 −3.34 
                 3.12 
                 3.46 
                 −1.14 
                 NP 
                 forodesine, 9-deaza-9-(3- 
               
               
                   
                 phosphorylase (Inosine 
                   
                   
                   
                   
                   
                 thienylmethyl)guanine 
               
               
                   
                 phosphorylase) (PNP). 
               
               
                 Ssc.19873.1.S1_at 
                 Collagen alpha 1(XVII) chain 
                 −2.37 
                 3.02 
                 −1.55 
                 2.18 
                 COL17A1 
                 collagenase 
               
               
                   
                 (Bullous pemphigoid antigen 2) 
               
               
                 Ssc.20904.1.A1_at 
                 RAC-gamma serine/threonine- 
                 −1.34 
                 3.01 
                 −2.18 
                 1.23 
                 AKT3 
                 enzastaurin 
               
               
                   
                 protein kinase (RAC-PK-gamma) 
               
               
                   
                 (Protein kinase Akt-3) 
               
               
                   
                 (Protein kinase B, gamma) (PKB 
               
               
                   
                 gamma) (STK-2) 
               
               
                 Ssc.26646.1.S1_at 
                 Glutamate receptor 1 
                 −1.10 
                 2.91 
                 −5.42 
                 −3.43 
                 GRIA1 
                 talampanel, Org 24448, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 LY451395, tezampanel 
               
               
                 Ssc.15312.1.S1_at 
                 Histone deacetylase 4 (HD4) 
                 −1.93 
                 2.85 
                 −2.41 
                 1.20 
                 HDAC4 
                 tributyrin, PXD101, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pyroxamide, vorinostat, FR 
               
               
                   
                   
                   
                   
                   
                   
                   
                 901228 
               
               
                 Ssc.24889.1.S1_at 
                 Arachidonate 12-lipoxygenase, 
                 1.97 
                 2.83 
                 −1.18 
                 −2.78 
                 ALOX12 
                 sulfasalazine, balsalazide, 5- 
               
               
                   
                 12S-type 
                   
                   
                   
                   
                   
                 aminosalicylic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 masoprocol, verteporfin 
               
               
                 Ssc.12630.1.A1_at 
                 Sodium/potassium-transporting 
                 2.97 
                 2.81 
                 −7.30 
                 −2.03 
                 ATP1A1 
                 digoxin, omeprazole, 
               
               
                   
                 ATPase alpha-1 chain 
                   
                   
                   
                   
                   
                 ethacrynic acid, perphenazine 
               
               
                 Ssc.3040.1.S1_at 
                 Histone deacetylase 2 (HD2) 
                 −3.24 
                 2.79 
                 4.94 
                 4.72 
                 HDAC2 
                 tributyrin, PXD101, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pyroxamide, vorinostat, FR 
               
               
                   
                   
                   
                   
                   
                   
                   
                 901228 
               
               
                 Ssc.12791.1.A1_at 
                 3-hydroxy-3-methylglutaryl- 
                 3.27 
                 2.77 
                 1.77 
                 −2.56 
                 HMGCR 
                 aspirin/pravastatin, 
               
               
                   
                 coenzyme A reductase (HMG-CoA 
                   
                   
                   
                   
                   
                 lovastatin/niacin, 
               
               
                   
                 reductase) 
                   
                   
                   
                   
                   
                 ezetimibe/simvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/atorvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fluvastatin, cerivastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 atorvastatin, pravastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 simvastatin, lovastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 rosuvastatin 
               
               
                 Ssc.20685.1.S1_at 
                 Apoptosis regulator Bcl-2 
                 −2.22 
                 2.77 
                 2.58 
                 3.25 
                 BCL2 
                 oblimersen, (−)-gossypol 
               
               
                 Ssc.15965.1.S1_at 
                 Inward rectifier potassium 
                 4.68 
                 2.72 
                 −1.84 
                 −4.62 
                 KCNJ2 
                 nicorandil, amiodarone 
               
               
                   
                 channel 2 (Potassium channel, 
               
               
                   
                 inwardly rectifying, subfamily 
               
               
                   
                 J, member 2) (Inward rectifier 
               
               
                   
                 K+ channel Kir2.1) (Cardiac 
               
               
                   
                 inward rectifier potassium 
               
               
                   
                 channel) (IRK1). 
               
               
                 Ssc.19673.1.S1_at 
                 T-cell surface glycoprotein 
                 6.40 
                 2.70 
                 2.03 
                 −11.77 
                 CD3D 
                 visilizumab, MT103 
               
               
                   
                 CD3 delta chain precursor (T- 
               
               
                   
                 cell receptor T3 delta chain) 
               
               
                 Ssc.16127.1.S1_at 
                 Adrenocorticotropic hormone 
                 −1.67 
                 2.70 
                 −2.51 
                 −1.10 
                 MC2R 
                 cosyntropin, ACTH 
               
               
                   
                 receptor (ACTH receptor) 
               
               
                   
                 (ACTH-R) 
               
               
                 Ssc.11406.1.A1_a_at 
                 Interleukin-1 receptor, type I 
                 1.03 
                 2.70 
                 −2.44 
                 1.42 
                 IL1R1 
                 anakinra 
               
               
                   
                 precursor (IL-1R-1) (IL-1R- 
               
               
                   
                 alpha) (P80) (Antigen CD121a) 
               
               
                 Ssc.19937.1.S1_at 
                 Inosine-5′-monophosphate 
                 1.00 
                 2.69 
                 −1.47 
                 3.65 
                 IMPDH2 
                 thioguanine, VX-944, 
               
               
                   
                 dehydrogenase 2 (IMP 
                   
                   
                   
                   
                   
                 interferon alfa-2a/ribavirin, 
               
               
                   
                 dehydrogenase 2) 
                   
                   
                   
                   
                   
                 mycophenolic acid, ribavirin 
               
               
                 Ssc.818.1.S1_at 
                 RAF proto-oncogene 
                 −1.40 
                 2.56 
                 1.58 
                 1.98 
                 RAF1 
                 sorafenib 
               
               
                   
                 serine/threonine-protein 
               
               
                   
                 kinase 
               
               
                 Ssc.14129.1.A1_at 
                 4-aminobutyrate aminotransferase, 
                 6.91 
                 2.56 
                 −21.17 
                 −3.35 
                 ABAT 
                 valproic acid 
               
               
                   
                 mitochondrial precursor 
               
               
                   
                 (Gamma-amino-N-butyrate 
               
               
                   
                 transaminase) (GABA 
               
               
                   
                 transaminase) 
               
               
                 Ssc.13186.1.S1_at 
                 Cell division protein kinase 7 
                 −1.08 
                 2.38 
                 4.34 
                 1.24 
                 CDK7 
                 BMS-387032, flavopiridol 
               
               
                 Ssc.16167.1.S1_at 
                 Rho-associated protein kinase 
                 2.40 
                 2.32 
                 2.83 
                 3.00 
                 ROCK1 
                 fasudil, Y-27632 
               
               
                   
                 1 
               
               
                 Ssc.6418.1.S1_at 
                 Farnesyl-diphosphate 
                 −1.25 
                 2.31 
                 1.33 
                 1.08 
                 FDFT1 
                 TAK-475, zoledronic acid 
               
               
                   
                 farnesyltransferase 
               
               
                 Ssc.15829.1.S1_at 
                 Retinoic acid receptor alpha 
                 −1.73 
                 2.23 
                 −1.33 
                 −1.16 
                 RARA 
                 etretinate, adapalene, arsenic 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trioxide, 13-cis-retinoic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tazarotene, acitretin, retinoic 
               
               
                   
                   
                   
                   
                   
                   
                   
                 acid, 9-cis-retinoic acid 
               
               
                 Ssc.10142.1.A1_at 
                 Dihydropyrimidine 
                 2.06 
                 2.17 
                 1.13 
                 −2.68 
                 DPYD 
                 eniluracil 
               
               
                   
                 dehydrogenase [NADP+] (DPD) 
               
               
                   
                 (DHPDHase) (Dihydrouracil 
               
               
                   
                 dehydrogenase) (Dihydrothymine 
               
               
                   
                 dehydrogenase). 
               
               
                 Ssc.23505.1.S1_at 
                 Amine oxidase [flavin- 
                 −1.86 
                 2.17 
                 1.08 
                 1.20 
                 MAOA 
                 ladostigil, 1- 
               
               
                   
                 containing] A (Monoamine 
                   
                   
                   
                   
                   
                 ethylphenoxathiin 10,10- 
               
               
                   
                 oxidase) (MAO-A) 
                   
                   
                   
                   
                   
                 dioxide, dextroamphetamine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 procainamide, tranylcypromine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 phenelzine, isocarboxazid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benzphetamine, N-(2- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 indanyl)glycinamide 
               
               
                 Ssc.20438.1.S1_at 
                 Prostaglandin F2-alpha 
                 −3.20 
                 2.13 
                 5.28 
                 −38.97 
                 PTGFR 
                 tafluprost, travoprost, 
               
               
                   
                 receptor (Prostanoid FP 
                   
                   
                   
                   
                   
                 isopropyl unoprostone, 
               
               
                   
                 receptor) (PGF receptor) (PGF2 
                   
                   
                   
                   
                   
                 bimatoprost, latanoprost 
               
               
                   
                 alpha receptor). 
               
               
                 Ssc.4756.1.A1_at 
                 Adenosine A3 receptor 
                 2.15 
                 2.10 
                 1.88 
                 −1.81 
                 ADORA3 
                 adenosine, dyphylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aminophylline, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, caffeine 
               
               
                 Ssc.11302.1.S1_at 
                 Collagen alpha 1(III) chain 
                 −1.80 
                 2.02 
                 2.06 
                 1.26 
                 COL3A1 
                 collagenase 
               
               
                 Ssc.19400.2.A1_at 
                 Presenilin 2 (PS-2) (STM-2) 
                 −2.32 
                 1.99 
                 −5.30 
                 −3.44 
                 PSEN2 
                 (R)-flurbiprofen 
               
               
                   
                 (E5-1) (AD3LP) (AD5) 
               
               
                 Ssc.3059.1.S1_at 
                 Aldose reductase (AR) 
                 −1.74 
                 1.98 
                 −1.66 
                 2.49 
                 AKR1B1 
                 sorbinil, Zopolrestat (Alond, 
               
               
                   
                 (Aldehyde reductase). 
                   
                   
                   
                   
                   
                 Pfizer), zenarestat (Fujisawa, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Parke-Davis) 
               
               
                 Ssc.18051.1.S1_at 
                 cGMP-inhibited 3′,5′-cyclic 
                 −3.16 
                 1.96 
                 3.41 
                 2.32 
                 PDE3B 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase B (Cyclic 
                   
                   
                   
                   
                   
                 medorinone, aminophylline, 
               
               
                   
                 GMP inhibited 
                   
                   
                   
                   
                   
                 cilostazol, dipyridamole, 
               
               
                   
                 phosphodiesterase B) (CGI-PDE 
                   
                   
                   
                   
                   
                 amrinone, tolbutamide, 
               
               
                   
                 B) (CGIPDE1) (CGIP1) 
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline 
               
               
                 Ssc.2548.1.S1_at 
                 DNA polymerase epsilon p17 
                 2.27 
                 1.93 
                 −1.67 
                 −1.21 
                 POLE3 
                 gemcitabine 
               
               
                   
                 subunit (DNA polymerase 
               
               
                   
                 epsilon subunit 3) (Chromatin 
               
               
                   
                 accessibility complex 17) 
               
               
                   
                 (HuCHRAC17) (CHRAC-17). 
               
               
                 Ssc.11383.1.A1_at 
                 Glutamate receptor 3 precursor 
                 2.61 
                 1.85 
                 −1.87 
                 −2.43 
                 GRIA3 
                 talampanel, Org 24448, 
               
               
                   
                 (GluR-3) (GluR-C) (GluR-K3) 
                   
                   
                   
                   
                   
                 LY451395, tezampanel 
               
               
                   
                 (Glutamate receptor 
               
               
                   
                 ionotropic, AMPA 3) 
               
               
                 Ssc.8549.1.A1_at 
                 Guanylate cyclase soluble, 
                 1.11 
                 1.84 
                 −2.00 
                 −2.59 
                 GUCY1A3 
                 nitroglycerin, isosorbide-5- 
               
               
                   
                 alpha-3 chain (GCS-alpha-3) 
                   
                   
                   
                   
                   
                 mononitrate, isosorbide 
               
               
                   
                 (Soluble guanylate cyclase 
                   
                   
                   
                   
                   
                 dinitrate, nitroprusside, 
               
               
                   
                 large subunit) (GCS-alpha-1). 
                   
                   
                   
                   
                   
                 isosorbide 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dinitrate/hydralazine 
               
               
                 Ssc.12781.1.A1_at 
                 Toll-like receptor 4 
                 2.39 
                 1.83 
                 −1.52 
                 −6.10 
                 TLR4 
                 TAK-242 
               
               
                 Ssc.6301.1.S1_at 
                 Aromatic-L-amino-acid 
                 1.76 
                 1.80 
                 −4.91 
                 −1.88 
                 DDC 
                 carbidopa/entacapone/levodopa, 
               
               
                   
                 decarboxylase (AADC) (DOPA 
                   
                   
                   
                   
                   
                 carbidopa/levodopa, S(−)- 
               
               
                   
                 decarboxylase) 
                   
                   
                   
                   
                   
                 carbidopa, L-dopa 
               
               
                 Ssc.6801.1.S1_at 
                 Proto-oncogene tyrosine- 
                 −1.06 
                 1.69 
                 2.36 
                 −1.82 
                 YES1 
                 dasatinib 
               
               
                   
                 protein kinase YES 
               
               
                 Ssc.5371.1.S1_a_at 
                 DNA polymerase epsilon subunit 
                 10.16 
                 1.68 
                 −1.37 
                 −3.14 
                 POLE2 
                 gemcitabine 
               
               
                   
                 B (DNA polymerase II subunit B). 
               
               
                 Ssc.11572.1.A1_at 
                 Histone deacetylase 3 (HD3) 
                 −1.65 
                 1.67 
                 −1.55 
                 2.36 
                 HDAC3 
                 tributyrin, PXD101, 
               
               
                   
                 (RPD3-2) (SMAP45) 
                   
                   
                   
                   
                   
                 pyroxamide, MGCD0103, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vorinostat, FR 901228 
               
               
                 Ssc.23234.1.S1_at 
                 collagen, type XXIV, alpha 1 
                 −1.43 
                 1.66 
                 1.16 
                 1.76 
                 COL24A1 
                 collagenase 
               
               
                 Ssc.9565.1.S1_at 
                 Interferon-gamma receptor 
                 2.92 
                 1.63 
                 1.41 
                 −1.23 
                 IFNGR1 
                 interferon gamma-1b 
               
               
                   
                 alpha chain precursor (IFN- 
               
               
                   
                 gamma-R1) (CD119 antigen) 
               
               
                 Ssc.5021.1.S1_at 
                 Glutamate decarboxylase, 65 
                 −29.44 
                 1.62 
                 −10.79 
                 −5.61 
                 GAD2 
                 valproic acid 
               
               
                   
                 kDa isoform (GAD-65) (65 kDa 
               
               
                   
                 glutamic acid decarboxylase) 
               
               
                 Ssc.14326.1.A1_at 
                 Mitogen-activated protein 
                 12.63 
                 1.56 
                 −1.80 
                 −7.24 
                 MAPK13 
                 SCIO-469 
               
               
                   
                 kinase 13 (Stress-activated 
               
               
                   
                 protein kinase-4) (Mitogen- 
               
               
                   
                 activated protein kinase p38 
               
               
                   
                 delta) (MAP kinase p38 delta) 
               
               
                 Ssc.10591.1.A1_at 
                 Metabotropic glutamate 
                 −7.83 
                 1.54 
                 −1.31 
                 1.40 
                 GRM5 
                 fasoracetam 
               
               
                   
                 receptor 5 precursor (mGluR5) 
               
               
                 Ssc.30373.1.A1_at 
                 cGMP-specific 3′,5′-cyclic 
                 4.27 
                 1.52 
                 2.34 
                 4.09 
                 PDE5A 
                 dyphylline, nitroglycerin, DA- 
               
               
                   
                 phosphodiesterase 
                   
                   
                   
                   
                   
                 8159, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 sildenafil, dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aspirin/dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vardenafil, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tadalafil, theophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline 
               
               
                 Ssc.6710.1.A1_at 
                 Ribonucleoside-diphosphate 
                 −1.90 
                 1.44 
                 2.01 
                 −1.01 
                 RRM1 
                 gemcitabine, clofarabine, 
               
               
                   
                 reductase M1 chain 
                   
                   
                   
                   
                   
                 fludarabine phosphate 
               
               
                   
                 (Ribonucleotide reductase 
               
               
                   
                 large chain) 
               
               
                 Ssc.7139.1.S1_at 
                 Dihydrofolate reductase 
                 −1.13 
                 1.41 
                 −1.12 
                 2.06 
                 DHFR 
                 pyrimethamine, trimethoprim, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 iclaprim, methotrexate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 sulfisoxazole, triamterene, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 folic acid, trimetrexate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 LY231514, PT 523 
               
               
                 Ssc.5538.1.S1_at 
                 Carbonic anhydrase II 
                 8.09 
                 1.39 
                 −2.25 
                 −1.35 
                 CA2 
                 methazolamide, 
               
               
                   
                 (Carbonate dehydratase II) 
                   
                   
                   
                   
                   
                 hydrochlorothiazide, 
               
               
                   
                 (CA-II) (Carbonic anhydrase C) 
                   
                   
                   
                   
                   
                 acetazolamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trichloromethiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dorzolamide, chlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dorzolamide/timolol, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brinzolamide, chlorthalidone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benzthiazide, sulfacetamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 topiramate 
               
               
                 Ssc.5569.1.S1_at 
                 Thyroid hormone receptor alpha 
                 −10.22 
                 1.26 
                 1.26 
                 6.49 
                 THRA 
                 3,5-diiodothyropropionic acid, 
               
               
                   
                 (C-erbA-alpha) (c-erbA-1) 
                   
                   
                   
                   
                   
                 amiodarone, thyroxine, L- 
               
               
                   
                 (EAR-7) (EAR7) 
                   
                   
                   
                   
                   
                 triiodothyronine 
               
               
                 Ssc.10360.1.S1_at 
                 B-Raf proto-oncogene 
                 −2.15 
                 1.26 
                 3.09 
                 1.36 
                 BRAF 
                 sorafenib 
               
               
                   
                 serine/threonine-protein 
               
               
                   
                 kinase 
               
               
                 Ssc.19672.1.S1_at 
                 RAC-alpha serine/threonine- 
                 17.77 
                 1.25 
                 −19.82 
                 −2.11 
                 AKT1 
                 enzastaurin 
               
               
                   
                 protein kinase (RAC-PK-alpha) 
               
               
                   
                 (Protein kinase B) (PKB) (C- 
               
               
                   
                 AKT) 
               
               
                 Ssc.21011.1.S1_at 
                 Collagen alpha 2(I) chain 
                 −2.70 
                 1.24 
                 3.12 
                 −1.01 
                 COL1A2 
                 collagenase 
               
               
                 Ssc.5045.1.S1_at 
                 3-beta-hydroxysteroid- 
                 −1.55 
                 1.24 
                 2.19 
                 2.08 
                 EBP 
                 SR 31747 
               
               
                   
                 delta(8),delta(7)-isomerase 
               
               
                   
                 (Cholestenol delta-isomerase) 
               
               
                   
                 (Delta8-delta7 sterol 
               
               
                   
                 isomerase) (D8-D7 sterol 
               
               
                   
                 isomerase) (Emopamil-binding 
               
               
                   
                 protein) 
               
               
                 Ssc.8726.1.A1_at 
                 Amidophosphoribosyltransferase 
                 1.03 
                 1.24 
                 4.16 
                 −1.11 
                 PPAT 
                 6-mercaptopurine, thioguanine, 
               
               
                   
                 precursor (Glutamine 
                   
                   
                   
                   
                   
                 azathioprine 
               
               
                   
                 phosphoribosylpyrophosphate 
               
               
                   
                 amidotransferase) (ATASE) 
               
               
                   
                 (GPAT) 
               
               
                 Ssc.10219.1.A1_at 
                 Excitatory amino acid 
                 1.36 
                 1.24 
                 −3.38 
                 −1.03 
                 SLC1A6 
                 riluzole 
               
               
                   
                 transporter 4 (Sodium- 
               
               
                   
                 dependent glutamate/aspartate 
               
               
                   
                 transporter) 
               
               
                 Ssc.15999.1.A1_at 
                 Vascular endothelial growth 
                 1.24 
                 1.24 
                 18.52 
                 −11.02 
                 KDR 
                 AEE 788, sunitinib, AZD 2171, 
               
               
                   
                 factor receptor 2 precursor 
                   
                   
                   
                   
                   
                 pazopanib, XL647, CEP 7055, 
               
               
                   
                 (VEGFR-2) (Kinase insert 
                   
                   
                   
                   
                   
                 BMS-582664, KRN-951, vatalanib, 
               
               
                   
                 domain receptor) (Protein- 
                   
                   
                   
                   
                   
                 sorafenib, vandetanib, 
               
               
                   
                 tyrosine kinase receptor Flk- 
                   
                   
                   
                   
                   
                 pegaptanib 
               
               
                   
                 1) 
               
               
                 Ssc.9348.1.S1_at 
                 Peroxisome proliferator 
                 −1.05 
                 1.22 
                 −3.05 
                 −1.52 
                 PPARA 
                 NS-220, tesaglitazar, 
               
               
                   
                 activated receptor alpha 
                   
                   
                   
                   
                   
                 clofibrate, fenofibrate, 
               
               
                   
                 (PPAR-alpha) 
                   
                   
                   
                   
                   
                 docosahexaenoic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 gemfibrozil 
               
               
                 Ssc.1498.1.S1_at 
                 Proteasome subunit beta type 5 
                 −1.81 
                 1.19 
                 1.38 
                 5.94 
                 PSMB5 
                 bortezomib 
               
               
                   
                 precursor (Proteasome epsilon 
               
               
                   
                 chain) (Macropain epsilon 
               
               
                   
                 chain) (Multicatalytic 
               
               
                   
                 endopeptidase complex epsilon 
               
               
                   
                 chain) (Proteasome subunit X) 
               
               
                   
                 (Proteasome chain 6) 
               
               
                   
                 (Proteasome subunit MB1) 
               
               
                 Ssc.6934.1.A1_at 
                 Thymidylate synthase (EC 
                 −1.13 
                 1.19 
                 −1.11 
                 −2.81 
                 TYMS 
                 flucytosine, 5-fluorouracil, 
               
               
                   
                 2.1.1.45) (TS) (TSase) (OK/SW- 
                   
                   
                   
                   
                   
                 plevitrexed, nolatrexed, 
               
               
                   
                 cl.29) 
                   
                   
                   
                   
                   
                 capecitabine, trifluridine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 floxuridine, LY231514 
               
               
                 Ssc.28329.1.S1_at 
                 DNA polymerase beta 
                 1.14 
                 1.19 
                 1.07 
                 5.25 
                 POLB 
                 nelarabine, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 stavudine, trifluridine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vidarabine, zalcitabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 entecavir 
               
               
                 Ssc.16823.1.S1_at 
                 P2Y purinoceptor 12 (P2Y12) 
                 1.38 
                 1.19 
                 1.41 
                 1.11 
                 P2RY12 
                 prasugrel, AZD 6140 
               
               
                   
                 (P2Y12 platelet ADP receptor) 
                   
                   
                   
                   
                   
                 (Ticagrelor), clopidogrel 
               
               
                   
                 (P2Y(ADP)) (ADP-glucose 
               
               
                   
                 receptor) (ADPG-R) (P2Y(AC)) 
               
               
                   
                 (P2Y(cyc)) (P2T(AC)) (SP1999 
               
               
                 Ssc.19691.1.S1_at 
                 Platelet-activating factor 
                 1.59 
                 1.16 
                 3.01 
                 1.47 
                 PLA2G7 
                 darapladib 
               
               
                   
                 acetylhydrolase precursor (EC 
               
               
                   
                 3.1.1.47) (PAF 
               
               
                   
                 acetylhydrolase) (PAF 2- 
               
               
                   
                 acylhydrolase) (LDL-associated 
               
               
                   
                 phospholipase A2) (LDL-PLA(2)) 
               
               
                   
                 (2-acetyl-1- 
               
               
                   
                 alkylglycerophosphocholine 
               
               
                   
                 esterase) (1-alkyl-2- 
               
               
                   
                 acetylglycerophosphocholine 
               
               
                   
                 esterase) 
               
               
                 Ssc.15880.1.S1_at 
                 Cysteinyl leukotriene receptor 
                 2.86 
                 1.14 
                 −2.12 
                 −3.42 
                 CYSLTR2 
                 montelukast, zafirlukast 
               
               
                   
                 2 (CysLTR2) (PSEC0146) (HG57) 
               
               
                   
                 (HPN321) (hGPCR21) 
               
               
                 Ssc.11147.1.S1_at 
                 Aldehyde dehydrogenase, 
                 3.18 
                 1.13 
                 2.00 
                 −1.68 
                 ALDH2 
                 disulfiram, chlorpropamide 
               
               
                   
                 mitochondrial precursor (EC 
               
               
                   
                 1.2.1.3) (ALDH class 2) 
               
               
                   
                 (ALDHI) (ALDH-E2) 
               
               
                 Ssc.1908.1.S1_at 
                 FKBP-rapamycin associated 
                 1.99 
                 1.13 
                 −1.88 
                 −1.46 
                 FRAP1 
                 AP23573, temsirolimus, 
               
               
                   
                 protein (FRAP) (Rapamycin 
                   
                   
                   
                   
                   
                 tacrolimus, everolimus 
               
               
                   
                 target protein) 
               
               
                 Ssc.19700.1.S1_at 
                 Serine/threonine protein 
                 1.11 
                 1.13 
                 1.34 
                 1.09 
                 PPP3CB 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 phosphatase 2B catalytic 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                   
                 subunit, beta 
               
               
                 Ssc.30147.1.A1_at 
                 Fibroblast growth factor 
                 1.56 
                 1.13 
                 −1.05 
                 −1.18 
                 FGFR2 
                 palifermin 
               
               
                   
                 receptor 2 precursor (FGFR-2) 
               
               
                   
                 (Keratinocyte growth factor 
               
               
                   
                 receptor 2) 
               
               
                 Ssc.27232.1.S1_at 
                 Succinate semialdehyde 
                 2.06 
                 1.12 
                 −2.84 
                 −5.73 
                 ALDH5A1 
                 valproic acid 
               
               
                   
                 dehydrogenase, mitochondrial 
               
               
                   
                 precursor (NAD(+)-dependent 
               
               
                   
                 succinic semialdehyde 
               
               
                   
                 dehydrogenase) 
               
               
                 Ssc.10215.1.A1_at 
                 High-affinity cAMP-specific 
                 1.83 
                 1.12 
                 −8.48 
                 −15.51 
                 PDE8A 
                 dyphylline, nitroglycerin, 
               
               
                   
                 and IBMX-insensitive 3′,5′- 
                   
                   
                   
                   
                   
                 aminophylline, anagrelide, 
               
               
                   
                 cyclic phosphodiesterase 8A 
                   
                   
                   
                   
                   
                 milrinone, dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tolbutamide, theophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline 
               
               
                 Ssc.2767.2.S1_a_at 
                 Prostaglandin E2 receptor, EP3 
                 2.30 
                 1.12 
                 −1.59 
                 −6.78 
                 PTGER3 
                 prostaglandin E1 
               
               
                   
                 subtype (Prostanoid EP3 
               
               
                   
                 receptor) (PGE receptor, EP3 
               
               
                   
                 subtype) 
               
               
                 Ssc.15955.1.S1_at 
                 Antithrombin-III precursor 
                 −1.89 
                 1.12 
                 −2.06 
                 −2.42 
                 SERPINC1 
                 enoxaparin, SR-123781A, 
               
               
                   
                 (ATIII) (PRO0309) 
                   
                   
                   
                   
                   
                 fondaparinux 
               
               
                 Ssc.25040.1.S1_at 
                 Serine/threonine-protein 
                 −3.75 
                 1.11 
                 1.06 
                 −2.45 
                 CHEK1 
                 UCN-01 (7- 
               
               
                   
                 kinase Chk1 
                   
                   
                   
                   
                   
                 hydroxystaurosporine) 
               
               
                 Ssc.14488.1.S1_at 
                 Glutamate carboxypeptidase II 
                 −1.04 
                 1.10 
                 1.02 
                 1.69 
                 FOLH1 
                 capromab pendetide 
               
               
                   
                 (Membrane glutamate 
               
               
                   
                 carboxypeptidase) 
               
               
                 Ssc.1.1.S1_at 
                 3-oxo-5-alpha-steroid 4- 
                 −1.77 
                 1.05 
                 −4.11 
                 −1.09 
                 SRD5A2 
                 finasteride, dutasteride 
               
               
                   
                 dehydrogenase 2 (Steroid 5- 
               
               
                   
                 alpha-reductase 2) (SR type 2) 
               
               
                   
                 (5 alpha-SR2) 
               
               
                 Ssc.7581.1.A1_at 
                 FL cytokine receptor precursor 
                 1.69 
                 1.04 
                 −1.81 
                 1.01 
                 FLT3 
                 CHIR-258, sorafenib, 
               
               
                   
                 (Tyrosine-protein kinase 
                   
                   
                   
                   
                   
                 lestaurtinib, CGP 41251 
               
               
                   
                 receptor FLT3) (Stem cell 
               
               
                   
                 tyrosine kinase 1) (STK-1) 
               
               
                   
                 (CD135 antigen) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Day 60 prescription. 
               
             
          
           
               
                   
                   
                 Fold 
                 Fold 
                 Fold 
                 Fold 
                   
                   
               
               
                   
                   
                 Change 
                 Change 
                 Change 
                 Change 
               
               
                   
                   
                 D 7/ 
                 D 21/ 
                 D 60/ 
                 D 180/ 
                 Gene 
               
               
                 Probe ID 
                 Name 
                 Base 
                 Base 
                 Base 
                 Base 
                 Symbol 
                 DRUGS 
               
               
                   
               
             
          
           
               
                 Ssc.21108.1.S1_at 
                 Complement C5 
                 −17.35 
                 3.21 
                 618.80 
                 9.28 
                 C5 
                 eculizumab 
               
               
                 Ssc.9272.1.S1_at 
                 Tumor-associated calcium 
                 1.81 
                 3.94 
                 176.50 
                 2.07 
                 TACSTD1 
                 tucotuzumab celmoleukin 
               
               
                   
                 signal transducer 1 (EPCAM 
               
               
                   
                 antigen) 
               
               
                 Ssc.23793.1.S1_at 
                 T-cell surface antigen CD2 
                 −3.27 
                 79.25 
                 93.34 
                 5.20 
                 CD2 
                 alefacept, siplizumab 
               
               
                 Ssc.17245.1.S1_at 
                 Interleukin-13 receptor alpha- 
                 −1.99 
                 23.04 
                 21.92 
                 7.16 
                 IL13RA1 
                 cintredekin besudotox 
               
               
                   
                 1 chain 
               
               
                 Ssc.15999.1.A1_at 
                 Vascular endothelial growth 
                 1.24 
                 1.24 
                 18.52 
                 −11.02 
                 KDR 
                 AEE 788, sunitinib, AZD 2171, 
               
               
                   
                 factor receptor 2 
                   
                   
                   
                   
                   
                 pazopanib, XL647, CEP 7055, BMS- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 582664, KRN-951, vatalanib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 sorafenib, vandetanib, pegaptanib 
               
               
                 Ssc.27603.1.S1_at 
                 Endothelin B receptor 
                 5.30 
                 −3.27 
                 15.99 
                 1.23 
                 EDNRB 
                 bosentan, sitaxsentan, 
               
               
                   
                 precursor (ET-B) (Endothelin 
                   
                   
                   
                   
                   
                 atrasentan 
               
               
                   
                 receptor Non- selective type) 
               
               
                 Ssc.2714.1.S1_a_at 
                 Proto-oncogene tyrosine- 
                 −4.26 
                 9.56 
                 12.54 
                 3.93 
                 FYN 
                 dasatinib 
               
               
                   
                 protein kinase FYN 
               
               
                 SscAffx.20.1.S1_at 
                 T-cell surface glycoprotein 
                 −2.19 
                 14.07 
                 10.96 
                 3.62 
                 CD3G 
                 visilizumab, MT103 
               
               
                   
                 CD3 gamma chain 
               
               
                 Ssc.7176.1.A1_at 
                 C-X-C chemokine receptor type 
                 3.74 
                 10.91 
                 8.15 
                 1.68 
                 CXCR4 
                 JM 3100 
               
               
                   
                 4 (CXC-R4) (CXCR-4) 
               
               
                 Ssc.26200.1.S1_at 
                 Thyroid hormone receptor beta- 
                 3.49 
                 −1.56 
                 7.96 
                 2.52 
                 THRB 
                 3,5-diiodothyropropionic acid, 
               
               
                   
                 1 
                   
                   
                   
                   
                   
                 amiodarone, thyroxine, L- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 triiodothyronine 
               
               
                 Ssc.7297.1.S1_at 
                 Amine oxidase [flavin- 
                 1.16 
                 6.42 
                 7.02 
                 −1.13 
                 MAOB 
                 safinamide, ladostigil, 
               
               
                   
                 containing] B(Monoamine 
                   
                   
                   
                   
                   
                 rasagiline, selegiline, 
               
               
                   
                 oxidase) (MAO-B). 
                   
                   
                   
                   
                   
                 dextroamphetamine, procainamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tranylcypromine, phenelzine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isocarboxazid, benzphetamine 
               
               
                 Ssc.9019.1.A1_at 
                 Atrial natriuretic peptide 
                 −1.09 
                 −1.69 
                 5.31 
                 1.18 
                 NPR3 
                 nesiritide 
               
               
                   
                 clearance receptor precursor 
               
               
                   
                 (ANP-C) (ANPRC) 
               
               
                 Ssc.20438.1.S1_at 
                 Prostaglandin F2-alpha 
                 −3.20 
                 2.13 
                 5.28 
                 −38.97 
                 PTGFR 
                 tafluprost, travoprost, 
               
               
                   
                 receptor 
                   
                   
                   
                   
                   
                 isopropyl unoprostone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 bimatoprost, latanoprost 
               
               
                 Ssc.3040.1.S1_at 
                 Histone deacetylase 2 (HD2) 
                 −3.24 
                 2.79 
                 4.94 
                 4.72 
                 HDAC2 
                 tributyrin, PXD101, pyroxamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vorinostat, FR 901228 
               
               
                 Ssc.26325.1.S1_at 
                 Cystic fibrosis transmembrane 
                 1.60 
                 −5.71 
                 4.77 
                 −8.99 
                 CFTR 
                 SP 303 
               
               
                   
                 conductance regulator (CFTR) 
               
               
                 Ssc.12845.1.S1_at 
                 Cell division protein kinase 6 
                 −6.56 
                 5.40 
                 4.77 
                 5.13 
                 CDK6 
                 PD-0332991, flavopiridol 
               
               
                 Ssc.13186.1.S1_at 
                 Cell division protein kinase 7 
                 −1.08 
                 2.38 
                 4.34 
                 1.24 
                 CDK7 
                 BMS-387032, flavopiridol 
               
               
                 Ssc.8726.1.A1_at 
                 Amidophosphoribosyltransferase 
                 1.03 
                 1.24 
                 4.16 
                 −1.11 
                 PPAT 
                 6-mercaptopurine, thioguanine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 azathioprine 
               
               
                 Ssc.15374.1.S1_at 
                 COL14A1 protein 
                 1.10 
                 −17.71 
                 3.79 
                 2.24 
                 COL14A1 
                 collagenase 
               
               
                 Ssc.1147.1.A1_at 
                 Lipoprotein lipase 
                 4.05 
                 −5.49 
                 3.78 
                 −8.08 
                 LPL 
                 nicotinic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lovastatin/niacin 
               
               
                 Ssc.15878.1.S1_at 
                 Serine/threonine protein 
                 1.85 
                 3.22 
                 3.62 
                 −1.49 
                 PPP3CA 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 phosphatase 2B catalytic 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                   
                 subunit, alpha 
               
               
                 Ssc.26351.1.S1_at 
                 cAMP-specific 3′,5′-cyclic 
                 4.67 
                 4.99 
                 3.61 
                 −1.15 
                 PDE4D 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase 4D 
                   
                   
                   
                   
                   
                 arofylline, tetomilast, L 869298, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aminophylline, anagrelide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cilomilast, milrinone, rolipram, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 caffeine 
               
               
                 Ssc.15801.1.A1_at 
                 Protein kinase C, beta 
                 3.36 
                 6.36 
                 3.53 
                 −4.98 
                 PRKCB1 
                 enzastaurin, ruboxistaurin 
               
               
                 Ssc.10055.1.A1_at 
                 Alpha platelet-derived growth 
                 −2.14 
                 −1.46 
                 3.52 
                 −1.14 
                 PDGFRA 
                 sunitinib, axitinib, imatinib, 
               
               
                   
                 factor receptor 
                   
                   
                   
                   
                   
                 becaplermin 
               
               
                 Ssc.24966.1.S1_at 
                 Purine nucleoside 
                 −3.34 
                 3.12 
                 3.46 
                 −1.14 
                 NP 
                 forodesine, 9-deaza-9-(3- 
               
               
                   
                 phosphorylase 
                   
                   
                   
                   
                   
                 thienylmethyl)guanine 
               
               
                 Ssc.18051.1.S1_at 
                 cGMP-inhibited 3′,5′-cyclic 
                 −3.16 
                 1.96 
                 3.41 
                 2.32 
                 PDE3B 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase B 
                   
                   
                   
                   
                   
                 medorinone, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cilostazol, dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amrinone, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline 
               
               
                 Ssc.9523.1.A1_at 
                 Methylated-DNA--protein- 
                 1.55 
                 −1.17 
                 3.35 
                 1.47 
                 MGMT 
                 O6-benzylguanine 
               
               
                   
                 cysteine methyltransferase 
               
               
                 Ssc.16000.1.A1_at 
                 Vascular endothelial growth 
                 1.08 
                 −3.40 
                 3.34 
                 1.72 
                 FLT1 
                 sunitinib, axitinib, CEP 7055 
               
               
                   
                 factor receptor 1 
               
               
                 Ssc.26328.1.S1_at 
                 C-C chemokine receptor type 5 
                 −2.53 
                 5.61 
                 3.25 
                 1.29 
                 CCR5 
                 maraviroc, vicriviroc, SCH 
               
               
                   
                 (CCR5) (CD195 antigen). 
                   
                   
                   
                   
                   
                 351125 
               
               
                 Ssc.17224.1.S1_at 
                 Toll-like receptor 8 
                 1.17 
                 6.49 
                 3.13 
                 −1.52 
                 TLR8 
                 resiquimod 
               
               
                 Ssc.21011.1.S1_at 
                 Collagen alpha 2(I) chain 
                 −2.70 
                 1.24 
                 3.12 
                 −1.01 
                 COL1A2 
                 collagenase 
               
               
                 Ssc.10360.1.S1_at 
                 B-Raf proto-oncogene 
                 −2.15 
                 1.26 
                 3.09 
                 1.36 
                 BRAF 
                 sorafenib 
               
               
                   
                 serine/threonine-protein 
               
               
                   
                 kinase 
               
               
                 Ssc.19532.1.S1_at 
                 Guanylate cyclase soluble, 
                 −4.28 
                 12.74 
                 3.04 
                 2.13 
                 GUCY1B3 
                 nitroglycerin, isosorbide-5- 
               
               
                   
                 beta-1 chain 
                   
                   
                   
                   
                   
                 mononitrate, isosorbide 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dinitrate, nitroprusside, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isosorbide dinitrate/hydralazine 
               
               
                 Ssc.19691.1.S1_at 
                 Platelet-activating factor 
                 1.59 
                 1.16 
                 3.01 
                 1.47 
                 PLA2G7 
                 darapladib 
               
               
                   
                 acetylhydrolase precursor 
               
               
                 Ssc.17155.1.A1_at 
                 heparanase; heparanase-1 
                 4.81 
                 5.38 
                 2.98 
                 −1.83 
                 HPSE 
                 heparanase inhibitor PI-88 
               
               
                 Ssc.15932.1.S1_at 
                 Integrin alpha-V precursor 
                 −6.15 
                 5.79 
                 2.94 
                 3.14 
                 ITGAV 
                 abciximab, CNTO 95, EMD121974 
               
               
                 Ssc.16167.1.S1_at 
                 Rho-associated protein kinase 1 
                 2.40 
                 2.32 
                 2.83 
                 3.00 
                 ROCK1 
                 fasudil, Y-27632 
               
               
                 Ssc.62.2.S1_a_at 
                 Interleukin-6 (IL-6) 
                 1.89 
                 −6.32 
                 2.77 
                 −1.04 
                 IL6 
                 tocilizumab 
               
               
                 Ssc.11246.1.A1_at 
                 Protein kinase C, alpha 
                 −5.96 
                 −4.78 
                 2.68 
                 2.46 
                 PRKCA 
                 L-threo-safingol 
               
               
                 Ssc.11381.1.S1_at 
                 Interferon-alpha/beta receptor 
                 10.45 
                 8.08 
                 2.61 
                 −1.30 
                 IFNAR1 
                 interferon beta-1a, interferon 
               
               
                   
                 alpha 
                   
                   
                   
                   
                   
                 alfa-2b, interferon alfacon-1, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 PEG-interferon alfa-2a, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a/ribavirin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegintron, interferon beta-1b, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 IFNA2A 
               
               
                 Ssc.20685.1.S1_at 
                 Apoptosis regulator Bcl-2 
                 −2.22 
                 2.77 
                 2.58 
                 3.25 
                 BCL2 
                 oblimersen, (−)-gossypol 
               
               
                 Ssc.12937.1.S1_at 
                 Presenilin 1 (PS-1) (S182 
                 −14.09 
                 6.21 
                 2.48 
                 3.79 
                 PSEN1 
                 (R)-flurbiprofen 
               
               
                   
                 protein) 
               
               
                 Ssc.8500.1.A1_at 
                 Glutamate receptor 4 precursor 
                 −1.04 
                 −1.13 
                 2.39 
                 −7.80 
                 GRIA4 
                 talampanel, Org 24448, LY451395, 
               
               
                   
                 (GluR-4) (GluR4) (GluR-D) 
                   
                   
                   
                   
                   
                 tezampanel 
               
               
                   
                 (Glutamate receptor 
               
               
                   
                 ionotropic, AMPA 4) 
               
               
                 Ssc.6801.1.S1_at 
                 Proto-oncogene tyrosine- 
                 −1.06 
                 1.69 
                 2.36 
                 −1.82 
                 YES1 
                 dasatinib 
               
               
                   
                 protein kinase YES 
               
               
                 Ssc.30373.1.A1_at 
                 cGMP-specific 3′,5′-cyclic 
                 4.27 
                 1.52 
                 2.34 
                 4.09 
                 PDE5A 
                 dyphylline, nitroglycerin, DA- 
               
               
                   
                 phosphodiesterase 
                   
                   
                   
                   
                   
                 8159, aminophylline, sildenafil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aspirin/dipyridamole, vardenafil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tolbutamide, tadalafil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline 
               
               
                 Ssc.15886.1.S1_at 
                 Apopain precursor (Caspase-3) 
                 −3.02 
                 3.64 
                 2.31 
                 2.29 
                 CASP3 
                 IDN-6556 
               
               
                   
                 (CASP-3) 
               
               
                 Ssc.16114.1.S1_at 
                 Dihydropyridine-sensitive L- 
                 −1.96 
                 −4.18 
                 2.24 
                 3.65 
                 CACNA2D1 
                 bepridil, amlodipine, pregabalin 
               
               
                   
                 type, calcium channel alpha- 
               
               
                   
                 2/delta subunits 
               
               
                 Ssc.10256.1.A1_at 
                 cAMP-specific 3′,5′-cyclic 
                 −1.89 
                 6.74 
                 2.20 
                 2.44 
                 PDE4B 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase 4B (EC 
                   
                   
                   
                   
                   
                 arofylline, tetomilast, L 869298, 
               
               
                   
                 3.1.4.17) (DPDE4) (PDE32) 
                   
                   
                   
                   
                   
                 aminophylline, anagrelide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cilomilast, milrinone, rolipram, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 caffeine 
               
               
                 Ssc.5045.1.S1_at 
                 3-beta-hydroxysteroid- 
                 −1.55 
                 1.24 
                 2.19 
                 2.08 
                 EBP 
                 SR 31747 
               
               
                   
                 delta(8),delta(7)-isomerase 
               
               
                   
                 (Emopamil-binding protein) 
               
               
                 Ssc.204.1.S1_at 
                 Cytochrome P450 3A4 
                 1.97 
                 −3.35 
                 2.16 
                 −1.42 
                 CYP3A4 
                 ketoconazole 
               
               
                 Ssc.16186.1.S1_at 
                 T-cell surface glycoprotein 
                 9.00 
                 3.12 
                 2.12 
                 −5.66 
                 CD3E 
                 visilizumab, MT103, muromonab- 
               
               
                   
                 CD3 epsilon chain 
                   
                   
                   
                   
                   
                 CD3 
               
               
                 Ssc.1091.1.S1_at 
                 Collagen alpha 1(I) chain 
                 −3.27 
                 −17.59 
                 2.07 
                 1.03 
                 COL1A1 
                 collagenase 
               
               
                 Ssc.11302.1.S1_at 
                 Collagen alpha 1(III) chain 
                 −1.80 
                 2.02 
                 2.06 
                 1.26 
                 COL3A1 
                 collagenase 
               
               
                 Ssc.19673.1.S1_at 
                 T-cell surface glycoprotein 
                 6.40 
                 2.70 
                 2.03 
                 −11.77 
                 CD3D 
                 visilizumab, MT103 
               
               
                   
                 CD3 delta chain 
               
               
                 Ssc.6710.1.A1_at 
                 Ribonucleoside-diphosphate 
                 −1.90 
                 1.44 
                 2.01 
                 −1.01 
                 RRM1 
                 gemcitabine, clofarabine, 
               
               
                   
                 reductase M1 chain 
                   
                   
                   
                   
                   
                 fludarabine phosphate 
               
               
                   
                 (Ribonucleotide reductase 
               
               
                   
                 large chain) 
               
               
                 Ssc.11147.1.S1_at 
                 Aldehyde dehydrogenase, 
                 3.18 
                 1.13 
                 2.00 
                 −1.68 
                 ALDH2 
                 disulfiram, chlorpropamide 
               
               
                   
                 mitochondrial precursor 
               
               
                   
                 ((ALDHI) 
               
               
                 Ssc.1520.1.A1_at 
                 Proto-oncogene tyrosine- 
                 −1.05 
                 −1.88 
                 2.00 
                 2.39 
                 RET 
                 sunitinib 
               
               
                   
                 protein kinase receptor ret 
               
               
                 Ssc.30888.1.S1_at 
                 Voltage-dependent L-type 
                 2.92 
                 −2.72 
                 1.90 
                 −7.82 
                 CACNA1D 
                 MEM-1003, mibefradil, bepridil, 
               
               
                   
                 calcium channel alpha-1D 
                   
                   
                   
                   
                   
                 nisoldipine, isradipine, 
               
               
                   
                 subunit 
                   
                   
                   
                   
                   
                 nicardipine 
               
               
                 Ssc.15739.1.S1_at 
                 Cytokine receptor common gamma 
                 −1.12 
                 9.42 
                 1.90 
                 −1.28 
                 IL2RG 
                 aldesleukin, denileukin diftitox 
               
               
                   
                 chain (IL-2R gamma chain) 
               
               
                   
                 (CD132 antigen) 
               
               
                 Ssc.15822.1.S1_at 
                 Coagulation factor V 
                 1.92 
                 3.76 
                 1.89 
                 −1.75 
                 F5 
                 drotrecogin alfa 
               
               
                   
                 (Activated protein C cofactor) 
               
               
                 Ssc.4756.1.A1_at 
                 Adenosine A3 receptor. 
                 2.15 
                 2.10 
                 1.88 
                 −1.81 
                 ADORA3 
                 adenosine, dyphylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aminophylline, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, caffeine 
               
               
                 Ssc.12791.1.A1_at 
                 3-hydroxy-3-methylglutaryl- 
                 3.27 
                 2.77 
                 1.77 
                 −2.56 
                 HMGCR 
                 aspirin/pravastatin, 
               
               
                   
                 coenzyme A reductase (HMG-CoA 
                   
                   
                   
                   
                   
                 lovastatin/niacin, 
               
               
                   
                 reductase) 
                   
                   
                   
                   
                   
                 ezetimibe/simvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/atorvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fluvastatin, cerivastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 atorvastatin, pravastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 simvastatin, lovastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 rosuvastatin 
               
               
                 Ssc.27293.1.A1_at 
                 Hypoxanthine-guanine 
                 2.15 
                 −1.16 
                 1.63 
                 −7.14 
                 HPRT1 
                 6-mercaptopurine, thioguanine, 
               
               
                   
                 phosphoribosyltransferase 
                   
                   
                   
                   
                   
                 azathioprine 
               
               
                   
                 (HGPRT) 
               
               
                 Ssc.16189.1.S1_at 
                 Endothelin-1 receptor 
                 −1.11 
                 −2.54 
                 1.58 
                 −2.91 
                 EDNRA 
                 bosentan, avosentan, 
               
               
                   
                 (Endothelin A receptor) (ET-A) 
                   
                   
                   
                   
                   
                 clazosentan, ambrisentan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 sitaxsentan, ZD4054, SB 234551, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 TBC 3214, BSF 302146, PD 180988, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 atrasentan 
               
               
                 Ssc.818.1.S1_at 
                 RAF proto-oncogene 
                 −1.40 
                 2.56 
                 1.58 
                 1.98 
                 RAF1 
                 sorafenib 
               
               
                   
                 serine/threonine-protein 
               
               
                   
                 kinase 
               
               
                 Ssc.15748.2.S2_at 
                 T lymphocyte activation 
                 1.95 
                 −1.24 
                 1.54 
                 −3.12 
                 CD80 
                 abatacept 
               
               
                   
                 antigen CD80 
               
               
                 Ssc.19059.1.A1_at 
                 Type-1 angiotensin II receptor 
                 5.57 
                 −2.57 
                 1.50 
                 −11.08 
                 AGTR1 
                 amlodipine/olmesartan medoxomil, 
               
               
                   
                 (AT1) (AT1AR) 
                   
                   
                   
                   
                   
                 losartan/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 valsartan/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 candesartan cilexetil, olmesartan 
               
               
                   
                   
                   
                   
                   
                   
                   
                 medoxomil, irbesartan, losartan 
               
               
                   
                   
                   
                   
                   
                   
                   
                 potassium, telmisartan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 eprosartan, candesartan 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cilexetil/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/irbesartan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 eprosartan/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/telmisartan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/olmesartan 
               
               
                   
                   
                   
                   
                   
                   
                   
                 medoxomil, valsartan 
               
               
                 Ssc.18459.1.S1_at 
                 Amiloride-sensitive sodium 
                 1.97 
                 −2.41 
                 1.43 
                 −1.93 
                 SCNN1A 
                 triamterene/hydrochlorothiazide, 
               
               
                   
                 channel alpha-subunit 
                   
                   
                   
                   
                   
                 amiloride, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amiloride/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 triamterene 
               
               
                 Ssc.10287.1.A1_at 
                 Transforming growth factor 
                 1.41 
                 −4.54 
                 1.43 
                 1.67 
                 TGFB2 
                 AP-12009 
               
               
                   
                 beta 2 precursor (TGF-beta 2) 
               
               
                 Ssc.16823.1.S1_at 
                 P2Y purinoceptor 12 (P2Y12) 
                 1.38 
                 1.19 
                 1.41 
                 1.11 
                 P2RY12 
                 prasugrel, AZD 6140, clopidogrel 
               
               
                   
                 (P2Y12 platelet ADP receptor) 
               
               
                   
                 (P2Y(ADP)) 
               
               
                 Ssc.9565.1.S1_at 
                 Interferon-gamma receptor 
                 2.92 
                 1.63 
                 1.41 
                 −1.23 
                 IFNGR1 
                 interferon gamma-1b 
               
               
                   
                 alpha chain 
               
               
                 Ssc.9595.1.S1_at 
                 Beta platelet-derived growth 
                 3.48 
                 −3.60 
                 1.40 
                 1.65 
                 PDGFRB 
                 dasatinib, sunitinib, axitinib, 
               
               
                   
                 factor receptor 
                   
                   
                   
                   
                   
                 KRN-951, imatinib, sorafenib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 becaplermin 
               
               
                 Ssc.8046.1.A1_at 
                 peptidylprolyl isomerase A 
                 1.16 
                 −1.08 
                 1.39 
                 1.26 
                 PPIA 
                 N-methyl-4-Ile-cyclosporin 
               
               
                   
                 isoform 1; cyclophilin A; 
               
               
                 Ssc.1498.1.S1_at 
                 Proteasome subunit beta type 5 
                 −1.81 
                 1.19 
                 1.38 
                 5.94 
                 PSMB5 
                 bortezomib 
               
               
                 Ssc.7111.1.A1_at 
                 Ribonucleoside-diphosphate 
                 −13.13 
                 4.08 
                 1.37 
                 1.67 
                 RRM2 
                 gemcitabine, triapine, 
               
               
                   
                 reductase M2 chain 
                   
                   
                   
                   
                   
                 hydroxyurea, fludarabine 
               
               
                   
                 (Ribonucleotide reductase 
                   
                   
                   
                   
                   
                 phosphate 
               
               
                   
                 small chain) 
               
               
                 Ssc.19700.1.S1_at 
                 Serine/threonine protein 
                 1.11 
                 1.13 
                 1.34 
                 1.09 
                 PPP3CB 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 phosphatase 2B catalytic 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                   
                 subunit, beta 
               
               
                 Ssc.14258.1.S1_at 
                 Amyloid beta A4 protein 
                 1.87 
                 3.33 
                 1.34 
                 −1.02 
                 APP 
                 AAB-001 
               
               
                   
                 precursor (APP) (ABPP) 
               
               
                 Ssc.6418.1.S1_at 
                 Farnesyl-diphosphate 
                 −1.25 
                 2.31 
                 1.33 
                 1.08 
                 FDFT1 
                 TAK-475, zoledronic acid 
               
               
                   
                 farnesyltransferase 
               
               
                 Ssc.16096.2.S1_a_at 
                 Mast/stem cell growth factor 
                 −1.28 
                 −2.63 
                 1.30 
                 −4.71 
                 KIT 
                 dasatinib, sunitinib, KRN-951, 
               
               
                   
                 receptor 
                   
                   
                   
                   
                   
                 imatinib, sorafenib 
               
               
                 Ssc.29149.1.A1_at 
                 Mineralocorticoid receptor 
                 −2.18 
                 −2.78 
                 1.28 
                 −11.66 
                 NR3C2 
                 hydrochlorothiazide/spironolactone, 
               
               
                   
                 (MR) 
                   
                   
                   
                   
                   
                 fludrocortisone acetate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 drospirenone, spironolactone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 eplerenone 
               
               
                 Ssc.5569.1.S1_at 
                 Thyroid hormone receptor alpha 
                 −10.22 
                 1.26 
                 1.26 
                 6.49 
                 THRA 
                 3,5-diiodothyropropionic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amiodarone, thyroxine, L- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 triiodothyronine 
               
               
                 Ssc.26215.1.S1_at 
                 DNA polymerase epsilon p12 
                 −1.23 
                 −2.71 
                 1.19 
                 −1.04 
                 POLE4 
                 gemcitabine 
               
               
                   
                 subunit (DNA polymerase 
               
               
                   
                 epsilon subunit 4) 
               
               
                 Ssc.23234.1.S1_at 
                 collagen, type XXIV, alpha 1 
                 −1.43 
                 1.66 
                 1.16 
                 1.76 
                 COL24A1 
                 collagenase 
               
               
                 Ssc.10142.1.A1_at 
                 Dihydropyrimidine 
                 2.06 
                 2.17 
                 1.13 
                 −2.68 
                 DPYD 
                 eniluracil 
               
               
                   
                 dehydrogenase [NADP+] 
               
               
                 Ssc.3607.1.S1_at 
                 Interferon-alpha/beta receptor 
                 2.28 
                 4.65 
                 1.11 
                 −1.56 
                 IFNAR2 
                 interferon beta-1a, interferon 
               
               
                   
                 beta 
                   
                   
                   
                   
                   
                 alfa-2b, interferon alfacon-1, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 PEG-interferon alfa-2a, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a/ribavirin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegintron, interferon beta-1b, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 IFNA2A 
               
               
                 Ssc.14475.3.S1_a_at 
                 Peroxisome proliferator 
                 13.83 
                 −9.38 
                 1.09 
                 −2.85 
                 PPARG 
                 rosiglitazone, GI262570, 
               
               
                   
                 activated receptor gamma 
                   
                   
                   
                   
                   
                 pioglitazone, tesaglitazar, 
               
               
                   
                 (PPAR-gamma) 
                   
                   
                   
                   
                   
                 troglitazone 
               
               
                 Ssc.5000.1.A1_at 
                 Receptor protein-tyrosine 
                 −1.04 
                 −4.15 
                 1.08 
                 2.25 
                 ERBB2 
                 trastuzumab, BMS-599626, ARRY- 
               
               
                   
                 kinase erbB-2 
                   
                   
                   
                   
                   
                 334543, XL647, CP-724,714, HKI- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 272, lapatinib, erlotinib 
               
               
                 Ssc.23505.1.S1_at 
                 Amine oxidase [flavin- 
                 −1.86 
                 2.17 
                 1.08 
                 1.20 
                 MAOA 
                 ladostigil, 1-ethylphenoxathiin 
               
               
                   
                 containing] A (Monoamine 
                   
                   
                   
                   
                   
                 10,10-dioxide, dextroamphetamine, 
               
               
                   
                 oxidase) (MAO-A) 
                   
                   
                   
                   
                   
                 procainamide, tranylcypromine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 phenelzine, isocarboxazid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benzphetamine, N-(2- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 indanyl)glycinamide 
               
               
                 Ssc.19379.1.A1_at 
                 Voltage-dependent L-type 
                 1.83 
                 −1.34 
                 1.07 
                 −3.27 
                 CACNA1C 
                 clevidipine, MEM-1003, 
               
               
                   
                 calcium channel alpha-1C 
                   
                   
                   
                   
                   
                 amlodipine/olmesartan medoxomil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/benazepril, diltiazem, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 verapamil, mibefradil, bepridil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalapril/felodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/atorvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nisoldipine, isradipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 felodipine, nimodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nitrendipine, amlodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nicardipine, nifedipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trandolapril/verapamil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 diltiazem/enalapril 
               
               
                 Ssc.6713.1.S1_at 
                 Androgen receptor 
                 −1.47 
                 −11.56 
                 1.07 
                 −2.36 
                 AR 
                 estradiol valerate/testosterone 
               
               
                   
                 (Dihydrotestosterone receptor) 
                   
                   
                   
                   
                   
                 enanthate, estradiol 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cypionate/testosterone cypionate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 bicalutamide, flutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nandrolone decanoate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 testosterone cypionate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 medroxyprogesterone acetate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 oxandrolone, danazol, stanozolol, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 spironolactone, testosterone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 oxymetholone, testosterone 
               
               
                   
                   
                   
                   
                   
                   
                   
                 propionate, testosterone 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enanthate 
               
               
                 Ssc.28329.1.S1_at 
                 DNA polymerase beta 
                 1.14 
                 1.19 
                 1.07 
                 5.25 
                 POLB 
                 nelarabine, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 stavudine, trifluridine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vidarabine, zalcitabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 entecavir 
               
               
                 Ssc.25040.1.S1_at 
                 Serine/threonine-protein 
                 −3.75 
                 1.11 
                 1.06 
                 −2.45 
                 CHEK1 
                 UCN-01 (7-hydroxystaurosporine) 
               
               
                   
                 kinase Chk1 
               
               
                 Ssc.9781.1.S1_at 
                 Plasminogen activator 
                 −1.55 
                 −1.17 
                 1.04 
                 1.30 
                 SERPINE1 
                 drotrecogin alfa 
               
               
                   
                 inhibitor-1 (PAI-1) 
               
               
                   
                 (Endothelial plasminogen 
               
               
                   
                 activator inhibitor) (PAI) 
               
               
                 Ssc.16532.1.S1_at 
                 Cell division protein kinase 2 
                 −1.83 
                 −1.51 
                 1.04 
                 1.35 
                 CDK2 
                 BMS-387032, flavopiridol 
               
               
                   
                 (p33 protein kinase). 
               
               
                 Ssc.22797.1.S1_at 
                 DNA topoisomerase II, beta 
                 3.15 
                 −1.87 
                 1.02 
                 −2.91 
                 TOP2B 
                 novobiocin, etoposide, CPI- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 0004Na, pixantrone, becatecarin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 elsamitrucin, AQ4N, BN 80927, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tafluposide, mitoxantrone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 norfloxacin, dexrazoxane, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tirapazamine, TAS-103, XK469, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 gatifloxacin, valrubicin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 gemifloxacin, moxifloxacin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 nemorubicin, nalidixic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 epirubicin, doxorubicin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 daunorubicin 
               
               
                 Ssc.14488.1.S1_at 
                 Glutamate carboxypeptidase II 
                 −1.04 
                 1.10 
                 1.02 
                 1.69 
                 FOLH1 
                 capromab pendetide 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 Day 180 prescription. 
               
             
          
           
               
                   
                   
                 Fold 
                 Fold 
                 Fold 
                 Fold 
                   
                   
               
               
                   
                   
                 Change 
                 Change 
                 Change 
                 Change 
               
               
                   
                   
                 D 7/ 
                 D 21/ 
                 D 60/ 
                 D 180/ 
                 Gene 
               
               
                 Probe ID 
                 Name 
                 Base 
                 Base 
                 Base 
                 Base 
                 Symbol 
                 DRUGS 
               
               
                   
               
             
          
           
               
                 Ssc.11051.1.S1_at 
                 Cell division protein kinase 4 
                 1.44 
                 −7.67 
                 −4.96 
                 23.75 
                 CDK4 
                 PD-0332991, flavopiridol 
               
               
                 Ssc.28690.1.A1_at 
                 Histone deacetylase 6 (HD6) 
                 −1.92 
                 −1.57 
                 −3.58 
                 20.60 
                 HDAC6 
                 tributyrin, PXD101, pyroxamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vorinostat, FR 901228 
               
               
                 Ssc.21108.1.S1_at 
                 Complement C5 
                 −17.35 
                 3.21 
                 618.80 
                 9.28 
                 C5 
                 eculizumab 
               
               
                 Ssc.5569.1.S1_at 
                 Thyroid hormone receptor alpha 
                 −10.22 
                 1.26 
                 1.26 
                 6.49 
                 THRA 
                 3,5-diiodothyropropionic acid, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amiodarone, thyroxine, L- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 triiodothyronine 
               
               
                 Ssc.1498.1.S1_at 
                 Proteasome subunit beta type 5 
                 −1.81 
                 1.19 
                 1.38 
                 5.94 
                 PSMB5 
                 bortezomib 
               
               
                 Ssc.13460.1.A1_at 
                 Histone deacetylase 9 (HD9) 
                 −6.40 
                 5.13 
                 −1.79 
                 5.72 
                 HDAC9 
                 tributyrin, PXD101, pyroxamide, 
               
               
                   
                 (HD7B) (HD7). 
                   
                   
                   
                   
                   
                 vorinostat, FR 901228 
               
               
                 Ssc.28329.1.S1_at 
                 DNA polymerase beta 
                 1.14 
                 1.19 
                 1.07 
                 5.25 
                 POLB 
                 nelarabine, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 stavudine, trifluridine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vidarabine, zalcitabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 entecavir 
               
               
                 Ssc.23793.1.S1_at 
                 T-cell surface antigen CD2 
                 −3.27 
                 79.25 
                 93.34 
                 5.20 
                 CD2 
                 alefacept, siplizumab 
               
               
                 Ssc.12845.1.S1_at 
                 Cell division protein kinase 6 
                 −6.56 
                 5.40 
                 4.77 
                 5.13 
                 CDK6 
                 PD-0332991, flavopiridol 
               
               
                 Ssc.24528.1.S1_at 
                 Angiotensin-converting enzyme 
                 −1.61 
                 5.01 
                 2.33 
                 4.76 
                 ACE 
                 pentopril, perindoprilat, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/benazepril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lisinopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benazepril, enalapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 perindopril, captopril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalapril/felodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/moexipril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benazepril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/quinapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fosinopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 captopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalapril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 ramipril, moexipril, quinapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lisinopril, enalaprilat, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trandolapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trandolapril/verapamil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 diltiazem/enalapril, fosinopril 
               
               
                 Ssc.3040.1.S1_at 
                 Histone deacetylase 2 (HD2) 
                 −3.24 
                 2.79 
                 4.94 
                 4.72 
                 HDAC2 
                 tributyrin, PXD101, pyroxamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vorinostat, FR 901228 
               
               
                 Ssc.30373.1.A1_at 
                 cGMP-specific 3′,5′-cyclic 
                 4.27 
                 1.52 
                 2.34 
                 4.09 
                 PDE5A 
                 dyphylline, nitroglycerin, DA- 
               
               
                   
                 phosphodiesterase 
                   
                   
                   
                   
                   
                 8159, aminophylline, sildenafil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aspirin/dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vardenafil, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tadalafil, theophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline 
               
               
                 Ssc.2714.1.S1_a_at 
                 Proto-oncogene tyrosine- 
                 −4.26 
                 9.56 
                 12.54 
                 3.93 
                 FYN 
                 dasatinib 
               
               
                   
                 protein kinase FYN 
               
               
                 Ssc.12937.1.S1_at 
                 Presenilin 1 (PS-1) (S182 
                 −14.09 
                 6.21 
                 2.48 
                 3.79 
                 PSEN1 
                 (R)-flurbiprofen 
               
               
                   
                 protein). 
               
               
                 Ssc.19937.1.S1_at 
                 Inosine-5′-monophosphate 
                 1.00 
                 2.69 
                 −1.47 
                 3.65 
                 IMPDH2 
                 thioguanine, VX-944, interferon 
               
               
                   
                 dehydrogenase 2 
                   
                   
                   
                   
                   
                 alfa-2a/ribavirin, mycophenolic 
               
               
                   
                   
                   
                   
                   
                   
                   
                 acid, ribavirin 
               
               
                 Ssc.16114.1.S1_at 
                 Dihydropyridine-sensitive L- 
                 −1.96 
                 −4.18 
                 2.24 
                 3.65 
                 CACNA2D1 
                 bepridil, amlodipine, 
               
               
                   
                 type, calcium channel alpha- 
                   
                   
                   
                   
                   
                 pregabalin 
               
               
                   
                 2/delta 
               
               
                 SscAffx.20.1.S1_at 
                 T-cell surface glycoprotein 
                 −2.19 
                 14.07 
                 10.96 
                 3.62 
                 CD3G 
                 visilizumab, MT103 
               
               
                   
                 CD3 gamma chain 
               
               
                 Ssc.20685.1.S1_at 
                 Apoptosis regulator Bcl-2 
                 −2.22 
                 2.77 
                 2.58 
                 3.25 
                 BCL2 
                 oblimersen, (−)-gossypol 
               
               
                 Ssc.11443.1.A1_at 
                 Transcription factor p65 
                 −1.43 
                 −2.45 
                 −3.96 
                 3.24 
                 RELA 
                 NF-kappaB decoy 
               
               
                 Ssc.26290.1.S1_at 
                 Integrin beta-5 
                 −1.06 
                 −1.51 
                 −5.43 
                 3.24 
                 ITGB5 
                 EMD121974 
               
               
                 Ssc.15932.1.S1_at 
                 Integrin alpha-V 
                 −6.15 
                 5.79 
                 2.94 
                 3.14 
                 ITGAV 
                 abciximab, CNTO 95, EMD121974 
               
               
                 Ssc.14471.1.S1_at 
                 B-lymphocyte antigen CD19 
                 9.54 
                 3.30 
                 −10.32 
                 3.04 
                 CD19 
                 combotox, HD37-dgRTA, MT103 
               
               
                 Ssc.16167.1.S1_at 
                 Rho-associated protein kinase 1 
                 2.40 
                 2.32 
                 2.83 
                 3.00 
                 ROCK1 
                 fasudil, Y-27632 
               
               
                 Ssc.26200.1.S1_at 
                 Thyroid hormone receptor beta- 
                 3.49 
                 −1.56 
                 7.96 
                 2.52 
                 THRB 
                 3,5-diiodothyropropionic acid, 
               
               
                   
                 1. 
                   
                   
                   
                   
                   
                 amiodarone, thyroxine, L- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 triiodothyronine 
               
               
                 Ssc.3059.1.S1_at 
                 Aldose reductase (Aldehyde 
                 −1.74 
                 1.98 
                 −1.66 
                 2.49 
                 AKR1B1 
                 sorbinil, Zopolrestat (Alond, 
               
               
                   
                 reductase). 
                   
                   
                   
                   
                   
                 Pfizer), zenarestat (Fujisawa, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Parke-Davis) 
               
               
                 Ssc.11246.1.A1_at 
                 Protein kinase C, alpha 
                 −5.96 
                 −4.78 
                 2.68 
                 2.46 
                 PRKCA 
                 L-threo-safingol 
               
               
                 Ssc.10256.1.A1_at 
                 cAMP-specific 3′,5′-cyclic 
                 −1.89 
                 6.74 
                 2.20 
                 2.44 
                 PDE4B 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase 4B 
                   
                   
                   
                   
                   
                 arofylline, tetomilast, L 
               
               
                   
                   
                   
                   
                   
                   
                   
                 869298, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 anagrelide, cilomilast, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 milrinone, rolipram, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 caffeine 
               
               
                 Ssc.1598.1.S1_at 
                 Retinoic acid receptor RXR- 
                 −2.21 
                 −1.13 
                 −4.20 
                 2.42 
                 RXRB 
                 bexarotene, retinoic acid, 9- 
               
               
                   
                 beta 
                   
                   
                   
                   
                   
                 cis-retinoic acid 
               
               
                 Ssc.1520.1.A1_at 
                 Proto-oncogene tyrosine- 
                 −1.05 
                 −1.88 
                 2.00 
                 2.39 
                 RET 
                 sunitinib 
               
               
                   
                 protein kinase receptor ret 
               
               
                 Ssc.11572.1.A1_at 
                 Histone deacetylase 3 (HD3) 
                 −1.65 
                 1.67 
                 −1.55 
                 2.36 
                 HDAC3 
                 tributyrin, PXD101, pyroxamide, 
               
               
                   
                 (RPD3-2) (SMAP45). 
                   
                   
                   
                   
                   
                 MGCD0103, vorinostat, FR 901228 
               
               
                 Ssc.18051.1.S1_at 
                 cGMP-inhibited 3′,5′-cyclic 
                 −3.16 
                 1.96 
                 3.41 
                 2.32 
                 PDE3B 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase B 
                   
                   
                   
                   
                   
                 medorinone, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cilostazol, dipyridamole, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amrinone, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline 
               
               
                 Ssc.15886.1.S1_at 
                 Apopain precursor (Caspase-3) 
                 −3.02 
                 3.64 
                 2.31 
                 2.29 
                 CASP3 
                 IDN-6556 
               
               
                   
                 (CASP-3) 
               
               
                 Ssc.5000.1.A1_at 
                 Receptor protein-tyrosine 
                 −1.04 
                 −4.15 
                 1.08 
                 2.25 
                 ERBB2 
                 trastuzumab, BMS-599626, ARRY- 
               
               
                   
                 kinase erbB-2 
                   
                   
                   
                   
                   
                 334543, XL647, CP-724,714, HKI- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 272, lapatinib, erlotinib 
               
               
                 Ssc.15374.1.S1_at 
                 COL14A1 protein 
                 1.10 
                 −17.71 
                 3.79 
                 2.24 
                 COL14A1 
                 collagenase 
               
               
                 Ssc.19873.1.S1_at 
                 Collagen alpha 1(XVII) chain 
                 −2.37 
                 3.02 
                 −1.55 
                 2.18 
                 COL17A1 
                 collagenase 
               
               
                 Ssc.19532.1.S1_at 
                 Guanylate cyclase soluble, 
                 −4.28 
                 12.74 
                 3.04 
                 2.13 
                 GUCY1B3 
                 nitroglycerin, isosorbide-5- 
               
               
                   
                 beta-1 chain 
                   
                   
                   
                   
                   
                 mononitrate, isosorbide 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dinitrate, nitroprusside, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isosorbide dinitrate/hydralazine 
               
               
                 Ssc.5045.1.S1_at 
                 3-beta-hydroxysteroid- 
                 −1.55 
                 1.24 
                 2.19 
                 2.08 
                 EBP 
                 SR 31747 
               
               
                   
                 delta(8),delta(7)-isomerase 
               
               
                   
                 (EC 5.3.3.5) (Cholestenol 
               
               
                   
                 delta-isomerase) (Emopamil- 
               
               
                   
                 binding protein). 
               
               
                 Ssc.9272.1.S1_at 
                 Tumor-associated calcium 
                 1.81 
                 3.94 
                 176.50 
                 2.07 
                 TACSTD1 
                 tucotuzumab celmoleukin 
               
               
                   
                 signal transducer 1 (EPCAM 
               
               
                   
                 antigen) 
               
               
                 Ssc.7139.1.S1_at 
                 Dihydrofolate reductase 
                 −1.13 
                 1.41 
                 −1.12 
                 2.06 
                 DHFR 
                 pyrimethamine, trimethoprim, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 iclaprim, methotrexate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 sulfisoxazole, triamterene, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 folic acid, trimetrexate, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 LY231514, PT 523 
               
               
                 Ssc.818.1.S1_at 
                 RAF proto-oncogene 
                 −1.40 
                 2.56 
                 1.58 
                 1.98 
                 RAF1 
                 sorafenib 
               
               
                   
                 serine/threonine-protein 
               
               
                   
                 kinase 
               
               
                 Ssc.25168.1.S1_a_at 
                 Collagen alpha 1(XVI) chain 
                 −7.23 
                 −3.61 
                 −4.45 
                 1.87 
                 COL16A1 
                 collagenase 
               
               
                 Ssc.3737.1.S1_at 
                 Tubulin gamma-1 chain (Gamma-1 
                 −1.24 
                 −1.88 
                 −1.29 
                 1.82 
                 TUBG1 
                 epothilone B, ixabepilone, 
               
               
                   
                 tubulin) ( 
                   
                   
                   
                   
                   
                 colchicine/probenecid, XRP9881, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 E7389, AL 108, EC145, NPI-2358, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 milataxel, TPI 287, TTI-237, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 docetaxel, vinflunine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vinorelbine, vincristine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vinblastine, paclitaxel, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 podophyllotoxin, colchicine 
               
               
                 Ssc.23234.1.S1_at 
                 collagen, type XXIV, alpha 1 
                 −1.43 
                 1.66 
                 1.16 
                 1.76 
                 COL24A1 
                 collagenase 
               
               
                 Ssc.16000.1.A1_at 
                 Vascular endothelial growth 
                 1.08 
                 −3.40 
                 3.34 
                 1.72 
                 FLT1 
                 sunitinib, axitinib, CEP 7055 
               
               
                   
                 factor receptor 1 
               
               
                 Ssc.14488.1.S1_at 
                 Glutamate carboxypeptidase II 
                 −1.04 
                 1.10 
                 1.02 
                 1.69 
                 FOLH1 
                 capromab pendetide 
               
               
                 Ssc.7176.1.A1_at 
                 C-X-C chemokine receptor type 
                 3.74 
                 10.91 
                 8.15 
                 1.68 
                 CXCR4 
                 JM 3100 
               
               
                   
                 4 (CXC-R4) (CXCR-4) 
               
               
                 Ssc.10287.1.A1_at 
                 Transforming growth factor 
                 1.41 
                 −4.54 
                 1.43 
                 1.67 
                 TGFB2 
                 AP-12009 
               
               
                   
                 beta 2 
               
               
                 Ssc.7111.1.A1_at 
                 Ribonucleoside-diphosphate 
                 −13.13 
                 4.08 
                 1.37 
                 1.67 
                 RRM2 
                 gemcitabine, triapine, 
               
               
                   
                 reductase M2 chain 
                   
                   
                   
                   
                   
                 hydroxyurea, fludarabine 
               
               
                   
                   
                   
                   
                   
                   
                   
                 phosphate 
               
               
                 Ssc.9595.1.S1_at 
                 Beta platelet-derived growth 
                 3.48 
                 −3.60 
                 1.40 
                 1.65 
                 PDGFRB 
                 dasatinib, sunitinib, axitinib, 
               
               
                   
                 factor receptor 
                   
                   
                   
                   
                   
                 KRN-951, imatinib, sorafenib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 becaplermin 
               
               
                 Ssc.5826.1.A1_at 
                 Macrophage colony stimulating 
                 1.93 
                 −4.97 
                 −13.18 
                 1.61 
                 CSF1R 
                 sunitinib 
               
               
                   
                 factor I receptor 
               
               
                 Ssc.17518.1.S1_at 
                 Adenosine A1 receptor 
                 −3.16 
                 3.44 
                 −1.56 
                 1.58 
                 ADORA1 
                 adenosine, dyphylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aminophylline, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, caffeine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tecadenoson 
               
               
                 Ssc.19691.1.S1_at 
                 Platelet-activating factor 
                 1.59 
                 1.16 
                 3.01 
                 1.47 
                 PLA2G7 
                 darapladib 
               
               
                   
                 acetylhydrolase 
               
               
                 Ssc.9523.1.A1_at 
                 Methylated-DNA--protein- 
                 1.55 
                 −1.17 
                 3.35 
                 1.47 
                 MGMT 
                 O6-benzylguanine 
               
               
                   
                 cysteine methyltransferase 
               
               
                 Ssc.11406.1.A1_a_at 
                 Interleukin-1 receptor, type I 
                 1.03 
                 2.70 
                 −2.44 
                 1.42 
                 IL1R1 
                 anakinra 
               
               
                 Ssc.11085.1.S1_at 
                 Glucagon-like peptide 2 
                 −1.08 
                 −1.17 
                 −1.26 
                 1.40 
                 GLP2R 
                 teduglutide 
               
               
                   
                 receptor 
               
               
                 Ssc.10591.1.A1_at 
                 Metabotropic glutamate 
                 −7.83 
                 1.54 
                 −1.31 
                 1.40 
                 GRM5 
                 fasoracetam 
               
               
                   
                 receptor 5 
               
               
                 Ssc.9034.1.A1_at 
                 Proteinase activated receptor 1 
                 −1.29 
                 3.75 
                 −1.40 
                 1.37 
                 F2R 
                 chrysalin, argatroban, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 bivalirudin 
               
               
                 Ssc.10360.1.S1_at 
                 B-Raf proto-oncogene 
                 −2.15 
                 1.26 
                 3.09 
                 1.36 
                 BRAF 
                 sorafenib 
               
               
                   
                 serine/threonine-protein 
               
               
                   
                 kinase 
               
               
                 Ssc.16532.1.S1_at 
                 Cell division protein kinase 2 
                 −1.83 
                 −1.51 
                 1.04 
                 1.35 
                 CDK2 
                 BMS-387032, flavopiridol 
               
               
                 Ssc.9781.1.S1_at 
                 Plasminogen activator 
                 −1.55 
                 −1.17 
                 1.04 
                 1.30 
                 SERPINE1 
                 drotrecogin alfa 
               
               
                   
                 inhibitor-1 precursor (PAI-1) 
               
               
                   
                 (Endothelial plasminogen 
               
               
                   
                 activator inhibitor) (PAI) 
               
               
                 Ssc.26328.1.S1_at 
                 C-C chemokine receptor type 5 
                 −2.53 
                 5.61 
                 3.25 
                 1.29 
                 CCR5 
                 maraviroc, vicriviroc, SCH 
               
               
                   
                 (CCR5) (CD195 antigen) 
                   
                   
                   
                   
                   
                 351125 
               
               
                 Ssc.8046.1.A1_at 
                 peptidylprolyl isomerase A 
                 1.16 
                 −1.08 
                 1.39 
                 1.26 
                 PPIA 
                 N-methyl-4-Ile-cyclosporin 
               
               
                   
                 isoform 1; cyclophilin A; 
               
               
                 Ssc.11302.1.S1_at 
                 Collagen alpha 1(III) chain 
                 −1.80 
                 2.02 
                 2.06 
                 1.26 
                 COL3A1 
                 collagenase 
               
               
                 Ssc.13186.1.S1_at 
                 Cell division protein kinase 7 
                 −1.08 
                 2.38 
                 4.34 
                 1.24 
                 CDK7 
                 BMS-387032, flavopiridol 
               
               
                 Ssc.27603.1.S1_at 
                 Endothelin B receptor 
                 5.30 
                 −3.27 
                 15.99 
                 1.23 
                 EDNRB 
                 bosentan, sitaxsentan, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 atrasentan 
               
               
                 Ssc.27093.1.A1_at 
                 cAMP-specific 3′,5′-cyclic 
                 −6.34 
                 −2.27 
                 −7.97 
                 1.23 
                 PDE4C 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase 4C 
                   
                   
                   
                   
                   
                 arofylline, tetomilast, L 
               
               
                   
                   
                   
                   
                   
                   
                   
                 869298, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 anagrelide, cilomilast, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 milrinone, rolipram, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 caffeine 
               
               
                 Ssc.20904.1.A1_at 
                 RAC-gamma serine/threonine- 
                 −1.34 
                 3.01 
                 −2.18 
                 1.23 
                 AKT3 
                 enzastaurin 
               
               
                   
                 protein kinase 
               
               
                 Ssc.23505.1.S1_at 
                 Amine oxidase [flavin- 
                 −1.86 
                 2.17 
                 1.08 
                 1.20 
                 MAOA 
                 ladostigil, 1-ethylphenoxathiin 
               
               
                   
                 containing] A (Monoamine 
                   
                   
                   
                   
                   
                 10,10-dioxide, 
               
               
                   
                 oxidase) (MAO-A) 
                   
                   
                   
                   
                   
                 dextroamphetamine, procainamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tranylcypromine, phenelzine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isocarboxazid, benzphetamine, N- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (2-indanyl)glycinamide 
               
               
                 Ssc.15312.1.S1_at 
                 Histone deacetylase 4 (HD4) 
                 −1.93 
                 2.85 
                 −2.41 
                 1.20 
                 HDAC4 
                 tributyrin, PXD101, pyroxamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vorinostat, FR 901228 
               
               
                 Ssc.9019.1.A1_at 
                 Atrial natriuretic peptide 
                 −1.09 
                 −1.69 
                 5.31 
                 1.18 
                 NPR3 
                 nesiritide 
               
               
                   
                 clearance receptor 
               
               
                 Ssc.16160.1.S1_at 
                 T lymphocyte activation 
                 −1.55 
                 3.88 
                 −1.37 
                 1.18 
                 CD86 
                 abatacept 
               
               
                   
                 antigen CD86 
               
               
                 Ssc.1844.1.S1_at 
                 Atrial natriuretic peptide 
                 −1.94 
                 −1.06 
                 −1.63 
                 1.13 
                 NPR2 
                 nesiritide 
               
               
                   
                 receptor B 
               
               
                 Ssc.11171.1.S1_at 
                 Adenosine deaminase 
                 1.32 
                 −2.04 
                 −3.23 
                 1.12 
                 ADA 
                 pentostatin, vidarabine 
               
               
                 Ssc.16823.1.S1_at 
                 P2Y purinoceptor 12 (P2Y12) 
                 1.38 
                 1.19 
                 1.41 
                 1.11 
                 P2RY12 
                 prasugrel, AZD 6140, 
               
               
                   
                 (P2Y12 platelet ADP receptor) 
                   
                   
                   
                   
                   
                 clopidogrel 
               
               
                 Ssc.19700.1.S1_at 
                 Serine/threonine protein 
                 1.11 
                 1.13 
                 1.34 
                 1.09 
                 PPP3CB 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 phosphatase 2B catalytic 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                   
                 subunit, beta 
               
               
                 Ssc.26752.1.S1_at 
                 5-hydroxytryptamine 
                 −3.57 
                 1.22 
                 1.60 
                 1.08 
                 HTR3B 
                 cisapride, granisetron, 
               
               
                   
                 (serotonin) receptor 3B 
                   
                   
                   
                   
                   
                 ondansetron, fenfluramine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 palonosetron, mirtazapine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 alosetron, D-tubocurarine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 ergotamine, dolasetron 
               
               
                 Ssc.6418.1.S1_at 
                 Farnesyl-diphosphate 
                 −1.25 
                 2.31 
                 1.33 
                 1.08 
                 FDFT1 
                 TAK-475, zoledronic acid 
               
               
                   
                 farnesyltransferase 
               
               
                 Ssc.22477.1.S1_at 
                 Collagen alpha 1(IV) chain 
                 1.58 
                 −5.08 
                 −1.78 
                 1.04 
                 COL4A1 
                 collagenase 
               
               
                 Ssc.31192.1.S1_at 
                 Collagen alpha 1(XVIII) chain 
                 −1.89 
                 −1.36 
                 −19.06 
                 1.03 
                 COL18A1 
                 collagenase 
               
               
                 Ssc.1091.1.S1_at 
                 Collagen alpha 1(I) chain 
                 −3.27 
                 −17.59 
                 2.07 
                 1.03 
                 COL1A1 
                 collagenase 
               
               
                 Ssc.7581.1.A1_at 
                 FL cytokine receptor 
                 1.69 
                 1.04 
                 −1.81 
                 1.01 
                 FLT3 
                 CHIR-258, sorafenib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lestaurtinib, CGP 41251 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 Upregulated gene targets at all timepoints (Days 7, 21, 60, and 180 relative to baseline) of PAH progression with available drugs 
               
             
          
           
               
                   
                   
                 Fold 
                 Fold 
                 Fold 
                 Fold 
                   
                   
               
               
                   
                   
                 Change 
                 Change 
                 Change 
                 Change 
               
               
                   
                   
                 D 7/ 
                 D 21/ 
                 D 60/ 
                 D 180/ 
                 Gene 
               
               
                 Probe ID 
                 Name 
                 Base 
                 Base 
                 Base 
                 Base 
                 Symbol 
                 Drugs 
               
               
                   
               
             
          
           
               
                 Ssc.28329.1.S1_at 
                 DNA polymerase beta 
                 1.14 
                 1.19 
                 1.07 
                 5.25 
                 POLB 
                 nelarabine, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 stavudine, trifluridine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vidarabine, zalcitabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 entecavir 
               
               
                 Ssc.9272.1.S1_at 
                 Tumor-associated 
                 1.81 
                 3.94 
                 176.50 
                 2.07 
                 TACSTD1 
                 tucotusumab celmoleukin 
               
               
                   
                 calcium signal 
               
               
                   
                 transducer 1 (EPCAM 
               
               
                   
                 antigen) 
               
               
                 Ssc.7176.1.A1_at 
                 C-X-C chemokine 
                 3.74 
                 10.91 
                 8.15 
                 1.68 
                 CXCR4 
                 JM 3100 (1,1′-(1,4- 
               
               
                   
                 receptor type 4 
                   
                   
                   
                   
                   
                 phenylenebis(methylene))bis(1,4, 
               
               
                   
                 (CXC-R4) (CXCR-4) 
                   
                   
                   
                   
                   
                 8,11- 
               
               
                   
                 (CD184 antigen) 
                   
                   
                   
                   
                   
                 tetraazacyclotetradecane)octahydrochloride 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dihydrate) 
               
               
                 Ssc.19691.1.S1_at 
                 Platelet-activating 
                 1.59 
                 1.16 
                 3.01 
                 1.47 
                 PLA2G7 
                 darapladib 
               
               
                   
                 factor 
               
               
                   
                 acetylhydrolase 
               
               
                 Ssc.16823.1.S1_at 
                 P2Y purinoceptor 12 
                 1.38 
                 1.19 
                 1.41 
                 1.11 
                 P2RY12 
                 prasugrel, AZD 6140 
               
               
                   
                 (P2Y12) 
                   
                   
                   
                   
                   
                 (Ticagrelor), clopidogrel 
               
               
                 Ssc.19700.1.S1_at 
                 Serine/threonine 
                 1.11 
                 1.13 
                 1.34 
                 1.09 
                 PPP3CB 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 protein phosphatase 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                   
                 2B catalytic 
               
               
                   
                 subunit, beta 
               
               
                   
                 isoform 
               
               
                 Ssc.14258.1.S1_at 
                 Amyloid beta A4 
                 1.87 
                 3.33 
                 1.34 
                 −1.02 
                 APP 
                 Bapineuzumab (AAB-001) 
               
               
                   
                 protein 
               
               
                 Ssc.8726.1.A1_at 
                 Amidophosphoribosyltransferase 
                 1.03 
                 1.24 
                 4.16 
                 −1.11 
                 PPAT 
                 thioguanine, azathioprine, 6- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 mercaptopurine, 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 Upregulated gene targets at Days 21 and 60 (relative to baseline) of PAH progression with available drugs 
               
             
          
           
               
                   
                   
                 Fold 
                 Fold 
                 Fold 
                 Fold 
                   
                   
               
               
                   
                   
                 Change 
                 Change 
                 Change 
                 Change 
               
               
                   
                   
                 D 7/ 
                 D 21 
                 D 60/ 
                 D 180/ 
                 Gene 
               
               
                 Probe ID 
                 Name 
                 Base 
                 Base 
                 Base 
                 Base 
                 Symbol 
                 Drugs 
               
               
                   
               
             
          
           
               
                 Ssc.21108.1.S1_at 
                 Complement C5 
                 −17.35 
                 3.21 
                 618.80 
                 9.28 
                 C5 
                 eculizumab 
               
               
                 Ssc.9272.1.S1_at 
                 Tumor-associated 
                 1.81 
                 3.94 
                 176.50 
                 2.07 
                 TACSTD1 
                 tucotuzumab celmoleukin 
               
               
                   
                 calcium signal 
               
               
                   
                 transducer 1 
               
               
                 Ssc.23793.1.S1_at 
                 T-cell surface 
                 −3.27 
                 79.25 
                 93.34 
                 5.20 
                 CD2 
                 alefacept, siplizumab 
               
               
                   
                 antigen CD2 
               
               
                 Ssc.17245.1.S1_at 
                 Interleukin-13 
                 −1.99 
                 23.04 
                 21.92 
                 7.16 
                 IL13RA1 
                 cintredekin besudotox 
               
               
                   
                 receptor alpha-1 
               
               
                   
                 chain 
               
               
                 Ssc.15999.1.A1_at 
                 Vascular endothelial 
                 1.24 
                 1.24 
                 18.52 
                 −11.02 
                 KDR 
                 AEE 788, sunitinib, AZD 2171, 
               
               
                   
                 growth factor 
                   
                   
                   
                   
                   
                 pazopanib, XL647, CEP 7055, 
               
               
                   
                 receptor 2 
                   
                   
                   
                   
                   
                 BMS-582664, KRN-951, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vatalanib, sorafenib, vandetanib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegaptanib 
               
               
                 Ssc.2714.1.S1_a_at 
                 Proto-oncogene 
                 −4.26 
                 9.56 
                 12.54 
                 3.93 
                 FYN 
                 dasatinib 
               
               
                   
                 tyrosine-protein 
               
               
                   
                 kinase FYN 
               
               
                 SscAffx.20.1.S1_at 
                 T-cell surface 
                 −2.19 
                 14.07 
                 10.96 
                 3.62 
                 CD3G 
                 visilizumab, MT103 
               
               
                   
                 glycoprotein CD3 
               
               
                   
                 gamma chain 
               
               
                 Ssc.7176.1.A1_at 
                 C-X-C chemokine 
                 3.74 
                 10.91 
                 8.15 
                 1.68 
                 CXCR4 
                 JM 3100 
               
               
                   
                 receptor type 4 
               
               
                   
                 (CXC-R4) (CXCR-4) ( 
               
               
                 Ssc.7297.1.S1_at 
                 Amine oxidase 
                 1.16 
                 6.42 
                 7.02 
                 −1.13 
                 MAOB 
                 safinamide, ladostigil, rasagiline, 
               
               
                   
                 [flavin-containing] 
                   
                   
                   
                   
                   
                 selegiline, dextroamphetamine, 
               
               
                   
                 B (EC 1.4.3.4) 
                   
                   
                   
                   
                   
                 procainamide, tranylcypromine, 
               
               
                   
                 (Monoamine oxidase) 
                   
                   
                   
                   
                   
                 phenelzine, isocarboxazid, 
               
               
                   
                 (MAO-B). 
                   
                   
                   
                   
                   
                 benzphetamine 
               
               
                 Ssc.20438.1.S1_at 
                 Prostaglandin F2- 
                 −3.20 
                 2.13 
                 5.28 
                 −38.97 
                 PTGFR 
                 tafluprost, travoprost, isopropyl 
               
               
                   
                 alpha receptor (PGF2 
                   
                   
                   
                   
                   
                 unoprostone, bimatoprost, latanoprost 
               
               
                   
                 alpha receptor). 
               
               
                 Ssc.3040.1.S1_at 
                 Histone deacetylase 
                 −3.24 
                 2.79 
                 4.94 
                 4.72 
                 HDAC2 
                 tributyrin, PXD101, pyroxamide, 
               
               
                   
                 2 (HD2). 
                   
                   
                   
                   
                   
                 vorinostat, FR 901228 
               
               
                 Ssc.12845.1.S1_at 
                 Cell division 
                 −6.56 
                 5.40 
                 4.77 
                 5.13 
                 CDK6 
                 PD-0332991, flavopiridol 
               
               
                   
                 protein kinase 6 (E 
               
               
                 Ssc.13186.1.S1_at 
                 Cell division 
                 −1.08 
                 2.38 
                 4.34 
                 1.24 
                 CDK7 
                 BMS-387032, flavopiridol 
               
               
                   
                 protein kinase 7 
               
               
                 Ssc.8726.1.A1_at 
                 Amidophosphoribosyl- 
                 1.03 
                 1.24 
                 4.16 
                 −1.11 
                 PPAT 
                 6-mercaptopurine, thioguanine, 
               
               
                   
                 transferase 
                   
                   
                   
                   
                   
                 azathioprine 
               
               
                 Ssc.15878.1.S1_at 
                 Serine/threonine 
                 1.85 
                 3.22 
                 3.62 
                 −1.49 
                 PPP3CA 
                 ISAtx-247, tacrolimus, pimecrolimus, 
               
               
                   
                 protein phosphatase 
                   
                   
                   
                   
                   
                 cyclosporin A 
               
               
                   
                 2B catalytic 
               
               
                   
                 subunit, alpha 
               
               
                   
                 isoform 
               
               
                 Ssc.26351.1.S1_at 
                 cAMP-specific 3′,5′- 
                 4.67 
                 4.99 
                 3.61 
                 −1.15 
                 PDE4D 
                 dyphylline, nitroglycerin, arofylline, 
               
               
                   
                 cyclic 
                   
                   
                   
                   
                   
                 tetomilast, L 869298, aminophylline, 
               
               
                   
                 phosphodiesterase 4D 
                   
                   
                   
                   
                   
                 anagrelide, cilomilast, milrinone, 
               
               
                   
                 (EC 3.1.4.17) 
                   
                   
                   
                   
                   
                 rolipram, dipyridamole, L-826,141, 
               
               
                   
                 (DPDE3) (PDE43). 
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, theophylline, 
               
               
                   
                 [Source: Uniprot/ 
                   
                   
                   
                   
                   
                 pentoxifylline, caffeine 
               
               
                   
                 SWISSPROT; Acc: 
               
               
                   
                 Q08499] 
               
               
                 Ssc.15801.1.A1_at 
                 Protein kinase C, 
                 3.36 
                 6.36 
                 3.53 
                 −4.98 
                 PRKCB1 
                 enzastaurin, ruboxistaurin 
               
               
                   
                 beta type (EC 
               
               
                   
                 2.7.1.37) (PKC-beta) 
               
               
                   
                 (PKC-B). 
               
               
                   
                 [Source: Uniprot/ 
               
               
                   
                 SWISSPROT; Acc: 
               
               
                   
                 P05771] 
               
               
                 Ssc.24966.1.S1_at 
                 Purine nucleoside 
                 −3.34 
                 3.12 
                 3.46 
                 −1.14 
                 NP 
                 forodesine, 9-deaza-9-(3- 
               
               
                   
                 phosphorylase 
                   
                   
                   
                   
                   
                 thienylmethyl)guanine 
               
               
                 Ssc.18051.1.S1_at 
                 cGMP-inhibited 
                 −3.16 
                 1.96 
                 3.41 
                 2.32 
                 PDE3B 
                 dyphylline, nitroglycerin, medorinone, 
               
               
                   
                 3′,5′-cyclic 
                   
                   
                   
                   
                   
                 aminophylline, cilostazol, dipyridamole, 
               
               
                   
                 phosphodiesterase B 
                   
                   
                   
                   
                   
                 amrinone, tolbutamide, theophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline 
               
               
                 Ssc.26328.1.S1_at 
                 C-C chemokine 
                 −2.53 
                 5.61 
                 3.25 
                 1.29 
                 CCR5 
                 maraviroc, vicriviroc, SCH 351125 
               
               
                   
                 receptor type 5 (C-C 
               
               
                   
                 CKR-5) (CC-CKR-5) 
               
               
                   
                 (CCR-5) (CCR5) (HIV- 
               
               
                   
                 1 fusion coreceptor) 
               
               
                   
                 (CHEMR13) (CD195 
               
               
                   
                 antigen). 
               
               
                   
                 [Source: Uniprot/ 
               
               
                   
                 SWISSPROT; Acc: 
               
               
                   
                 P51681] 
               
               
                 Ssc.17224.1.S1_at 
                 Toll-like receptor 8 
                 1.17 
                 6.49 
                 3.13 
                 −1.52 
                 TLR8 
                 resiquimod 
               
               
                   
                 precursor. 
               
               
                   
                 [Source: Uniprot/ 
               
               
                   
                 SWISSPROT; Acc: 
               
               
                   
                 Q9NR97] 
               
               
                 Ssc.21011.1.S1_at 
                 Collagen alpha 2(I) 
                 −2.70 
                 1.24 
                 3.12 
                 −1.01 
                 COL1A2 
                 collagenase 
               
               
                   
                 chain precursor. 
               
               
                   
                 [Source: Uniprot/ 
               
               
                   
                 SWISSPROT; Acc: 
               
               
                   
                 P08123] 
               
               
                 Ssc.10360.1.S1_at 
                 B-Raf proto-oncogene 
                 −2.15 
                 1.26 
                 3.09 
                 1.36 
                 BRAF 
                 sorafenib 
               
               
                   
                 serine/threonine- 
               
               
                   
                 protein kinase (v- 
               
               
                   
                 Raf murine sarcoma 
               
               
                   
                 viral oncogene 
               
               
                   
                 homolog B1). 
               
               
                 Ssc.19532.1.S1_at 
                 Guanylate cyclase 
                 −4.28 
                 12.74 
                 3.04 
                 2.13 
                 GUCY1B3 
                 nitroglycerin, isosorbide-5-mononitrate, 
               
               
                   
                 soluble, beta-1 
                   
                   
                   
                   
                   
                 isosorbide dinitrate, nitroprusside, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isosorbide dinitrate/hydralazine 
               
               
                 Ssc.19691.1.S1_at 
                 Platelet-activating 
                 1.59 
                 1.16 
                 3.01 
                 1.47 
                 PLA2G7 
                 darapladib 
               
               
                   
                 factor 
               
               
                   
                 acetylhydrolase 
               
               
                 Ssc.17155.1.A1_at 
                 heparanase; 
                 4.81 
                 5.38 
                 2.98 
                 −1.83 
                 HPSE 
                 heparanase inhibitor PI-88 
               
               
                   
                 heparanase-1 
               
               
                 Ssc.15932.1.S1_at 
                 Integrin alpha-V 
                 −6.15 
                 5.79 
                 2.94 
                 3.14 
                 ITGAV 
                 abciximab, CNTO 95, EMD121974 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (Cilengitide) 
               
               
                 Ssc.11381.1.S1_at 
                 Interferon- 
                 10.45 
                 8.08 
                 2.61 
                 −1.30 
                 IFNAR1 
                 interferon beta-1a, interferon alfa-2b, 
               
               
                   
                 alpha/beta receptor 
                   
                   
                   
                   
                   
                 interferon alfacon-1, PEG-interferon alfa- 
               
               
                   
                 alpha chain 
                   
                   
                   
                   
                   
                 2a, interferon alfa-2a/ribavirin, 
               
               
                   
                 precursor (IFN- 
                   
                   
                   
                   
                   
                 pegintron, interferon beta-1b, IFNA2A 
               
               
                   
                 alpha-REC). 
               
               
                   
                 [Source: Uniprot/ 
               
               
                   
                 SWISSPROT; Acc: 
               
               
                   
                 P17181] 
               
               
                 Ssc.20685.1.S1_at 
                 Apoptosis regulator 
                 −2.22 
                 2.77 
                 2.58 
                 3.25 
                 BCL2 
                 Oblimersen (Augmerosen), 
               
               
                   
                 Bcl-2. 
               
               
                   
                 [Source: Uniprot/ 
               
               
                   
                 SWISSPROT; Acc: 
               
               
                   
                 P10415] 
               
               
                 Ssc.12937.1.S1_at 
                 Presenilin 1 (PS-1) 
                 −14.09 
                 6.21 
                 2.48 
                 3.79 
                 PSEN1 
                 (R)-flurbiprofen (Tarenflurbil) 
               
               
                   
                 (S182 protein). 
               
               
                 Ssc.6801.1.S1_at 
                 Proto-oncogene 
                 −1.06 
                 1.69 
                 2.36 
                 −1.82 
                 YES1 
                 dasatinib 
               
               
                   
                 tyrosine-protein 
               
               
                   
                 kinase YES 
               
               
                 Ssc.24528.1.S1_at 
                 Angiotensin- 
                 −1.61 
                 5.01 
                 2.33 
                 4.76 
                 ACE 
                 pentopril, perindoprilat, 
               
               
                   
                 converting enzyme 
                   
                   
                   
                   
                   
                 amlodipine/benazepril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lisinopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benazepril, enalapril, perindopril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 captopril, enalapril/felodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/moexipril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benazepril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/quinapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fosinopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 captopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalapril/hydrochlorothiazide, ramipril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 moexipril, quinapril, lisinopril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalaprilat, trandolapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trandolapril/verapamil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 diltiazem/enalapril, fosinopril 
               
               
                 Ssc.15886.1.S1_at 
                 Apopain (Caspase-3) 
                 −3.02 
                 3.64 
                 2.31 
                 2.29 
                 CASP3 
                 IDN-6556 
               
               
                   
                 (CASP-3 
               
               
                 Ssc.10256.1.A1_at 
                 cAMP-specific 3′,5′- 
                 −1.89 
                 6.74 
                 2.20 
                 2.44 
                 PDE4B 
                 dyphylline, nitroglycerin, arofylline, 
               
               
                   
                 cyclic 
                   
                   
                   
                   
                   
                 tetomilast, L 869298, aminophylline, 
               
               
                   
                 phosphodiesterase 4B 
                   
                   
                   
                   
                   
                 anagrelide, cilomilast, milrinone, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 rolipram, dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, theophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline, caffeine 
               
               
                 Ssc.5045.1.S1_at 
                 3-beta- 
                 −1.55 
                 1.24 
                 2.19 
                 2.08 
                 EBP 
                 SR 31747 
               
               
                   
                 hydroxysteroid- 
               
               
                   
                 delta(8),delta(7)- 
               
               
                   
                 isomerase 
               
               
                 Ssc.16145.1.A1_at 
                 5-hydroxytryptamine 
                 1.08 
                 2.10 
                 2.15 
                 5.45 
                 HTR2B 
                 risperidone, buspirone, blonanserin, 
               
               
                   
                 2B receptor (5-HT- 
                   
                   
                   
                   
                   
                 asenapine, eletriptan, epinastine, 
               
               
                   
                 2B) (Serotonin 
                   
                   
                   
                   
                   
                 fenfluramine, quetiapine, nefazodone, 
               
               
                   
                 receptor 2B). 
                   
                   
                   
                   
                   
                 mirtazapine, dihydroergotamine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 apomorphine, ergotamine 
               
               
                 Ssc.16186.1.S1_at 
                 T-cell surface 
                 9.00 
                 3.12 
                 2.12 
                 −5.66 
                 CD3E 
                 visilizumab, MT103, muromonab-CD3 
               
               
                   
                 glycoprotein CD3 
               
               
                   
                 epsilon chain 
               
               
                 Ssc.11302.1.S1_at 
                 Collagen alpha 
                 −1.80 
                 2.02 
                 2.06 
                 1.26 
                 COL3A1 
                 collagenase 
               
               
                   
                 1(III) chain 
               
               
                   
                 precursor. 
               
               
                 Ssc.19673.1.S1_at 
                 T-cell surface 
                 6.40 
                 2.70 
                 2.03 
                 −11.77 
                 CD3D 
                 visilizumab, MT103 
               
               
                   
                 glycoprotein CD3 
               
               
                   
                 delta chain 
               
               
                   
                 precursor (T-cell 
               
               
                   
                 receptor T3 delta 
               
               
                   
                 chain). 
               
               
                 Ssc.6710.1.A1_at 
                 Ribonucleoside- 
                 −1.90 
                 1.44 
                 2.01 
                 −1.01 
                 RRM1 
                 gemcitabine, clofarabine, fludarabine 
               
               
                   
                 diphosphate 
                   
                   
                   
                   
                   
                 phosphate 
               
               
                   
                 reductase M1 chain 
               
               
                   
                 (Ribonucleotide 
               
               
                   
                 reductase large 
               
               
                   
                 chain 
               
               
                 Ssc.11147.1.S1_at 
                 Aldehyde 
                 3.18 
                 1.13 
                 2.00 
                 −1.68 
                 ALDH2 
                 disulfiram, chlorpropamide 
               
               
                   
                 dehydrogenase, 
               
               
                   
                 mitochondrial 
               
               
                   
                 precursor (ALDH 
               
               
                   
                 class 2) (ALDHI) 
               
               
                   
                 (ALDH-E2). 
               
               
                 Ssc.15739.1.S1_at 
                 Cytokine receptor 
                 −1.12 
                 9.42 
                 1.90 
                 −1.28 
                 IL2RG 
                 aldesleukin, denileukin diftitox 
               
               
                   
                 common gamma chain 
               
               
                   
                 (Interleukin-2 
               
               
                   
                 receptor gamma 
               
               
                   
                 chain) (IL-2R gamma 
               
               
                   
                 chain) (CD132 
               
               
                   
                 antigen). 
               
               
                 Ssc.15822.1.S1_at 
                 Coagulation factor V 
                 1.92 
                 3.76 
                 1.89 
                 −1.75 
                 F5 
                 drotrecogin alfa 
               
               
                   
                 precursor (Activated 
               
               
                   
                 protein C cofactor). 
               
               
                 Ssc.4756.1.A1_at 
                 Adenosine A3 
                 2.15 
                 2.10 
                 1.88 
                 −1.81 
                 ADORA3 
                 adenosine, dyphylline, aminophylline, 
               
               
                   
                 receptor. 
                   
                   
                   
                   
                   
                 clofarabine, theophylline, caffeine 
               
               
                 Ssc.12791.1.A1_at 
                 3-hydroxy-3- 
                 3.27 
                 2.77 
                 1.77 
                 −2.56 
                 HMGCR 
                 aspirin/pravastatin, lovastatin/niacin, 
               
               
                   
                 methylglutaryl- 
                   
                   
                   
                   
                   
                 ezetimibe/simvastatin, 
               
               
                   
                 coenzyme A reductase 
                   
                   
                   
                   
                   
                 amlodipine/atorvastatin, fluvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cerivastatin, atorvastatin, pravastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 simvastatin, lovastatin, rosuvastatin 
               
               
                 Ssc.818.1.S1_at 
                 RAF proto-oncogene 
                 −1.40 
                 2.56 
                 1.58 
                 1.98 
                 RAF1 
                 sorafenib 
               
               
                   
                 serine/threonine- 
               
               
                   
                 protein kinase 
               
               
                 Ssc.16823.1.S1_at 
                 P2Y purinoceptor 12 
                 1.38 
                 1.19 
                 1.41 
                 1.11 
                 P2RY12 
                 prasugrel, AZD 6140 (Ticagrelor), 
               
               
                   
                 (P2Y12) (P2Y12 
                   
                   
                   
                   
                   
                 clopidogrel 
               
               
                   
                 platelet ADP 
               
               
                   
                 receptor) 
               
               
                 Ssc.9565.1.S1_at 
                 Interferon-gamma 
                 2.92 
                 1.63 
                 1.41 
                 −1.23 
                 IFNGR1 
                 interferon gamma-1b 
               
               
                   
                 receptor alpha chain 
               
               
                   
                 (CD119 antigen) 
               
               
                 Ssc.1498.1.S1_at 
                 Proteasome subunit 
                 −1.81 
                 1.19 
                 1.38 
                 5.94 
                 PSMB5 
                 bortezomib 
               
               
                   
                 beta type 5 
               
               
                 Ssc.7111.1.A1_at 
                 Ribonucleoside- 
                 −13.13 
                 4.08 
                 1.37 
                 1.67 
                 RRM2 
                 gemcitabine, triapine, hydroxyurea, 
               
               
                   
                 diphosphate 
                   
                   
                   
                   
                   
                 fludarabine phosphate 
               
               
                   
                 reductase M2 chain 
               
               
                 Ssc.19700.1.S1_at 
                 Serine/threonine 
                 1.11 
                 1.13 
                 1.34 
                 1.09 
                 PPP3CB 
                 ISAtx-247, tacrolimus, pimecrolimus, 
               
               
                   
                 protein phosphatase 
                   
                   
                   
                   
                   
                 cyclosporin A 
               
               
                   
                 2B catalytic 
               
               
                   
                 subunit, beta 
               
               
                 Ssc.14258.1.S1_at 
                 Amyloid beta A4 
                 1.87 
                 3.33 
                 1.34 
                 −1.02 
                 APP 
                 AAB-001 (Bapineuzumab) 
               
               
                   
                 protein 
               
               
                 Ssc.6418.1.S1_at 
                 Farnesyl-diphosphate 
                 −1.25 
                 2.31 
                 1.33 
                 1.08 
                 FDFT1 
                 TAK-475, zoledronic acid 
               
               
                   
                 farnesyltransferase 
               
               
                 Ssc.5569.1.S1_at 
                 Thyroid hormone 
                 −10.22 
                 1.26 
                 1.26 
                 6.49 
                 THRA 
                 3,5-diiodothyropropionic acid, 
               
               
                   
                 receptor alpha (C- 
                   
                   
                   
                   
                   
                 amiodarone, thyroxine, L-triiodothyronine 
               
               
                   
                 erbA-alpha) (c-erbA- 
               
               
                   
                 1) 
               
               
                 Ssc.23234.1.S1_at 
                 collagen, type XXIV, 
                 −1.43 
                 1.66 
                 1.16 
                 1.76 
                 COL24A1 
                 collagenase 
               
               
                   
                 alpha 1 
               
               
                 Ssc.10142.1.A1_at 
                 Dihydropyrimidine 
                 2.06 
                 2.17 
                 1.13 
                 −2.68 
                 DPYD 
                 eniluracil 
               
               
                   
                 dehydrogenase 
               
               
                   
                 [NADP+] 
               
               
                 Ssc.3607.1.S1_at 
                 Interferon- 
                 2.28 
                 4.65 
                 1.11 
                 −1.56 
                 IFNAR2 
                 interferon beta-1a, interferon alfa-2b, 
               
               
                   
                 alpha/beta receptor 
                   
                   
                   
                   
                   
                 interferon alfacon-1, PEG-interferon alfa- 
               
               
                   
                 beta chain 
                   
                   
                   
                   
                   
                 2a, interferon alfa-2a/ribavirin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegintron, interferon beta-1b, IFNA2A 
               
               
                 Ssc.23505.1.S1_at 
                 Amine oxidase 
                 −1.86 
                 2.17 
                 1.08 
                 1.20 
                 MAOA 
                 ladostigil, 1-ethylphenoxathiin 10,10- 
               
               
                   
                 [flavin-containing] A 
                   
                   
                   
                   
                   
                 dioxide, dextroamphetamine, procainamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tranylcypromine, phenelzine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isocarboxazid, benzphetamine, N-(2- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 indanyl)glycinamide 
               
               
                 Ssc.28329.1.S1_at 
                 DNA polymerase 
                 1.14 
                 1.19 
                 1.07 
                 5.25 
                 POLB 
                 nelarabine, clofarabine, stavudine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trifluridine, vidarabine, zalcitabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 entecavir 
               
               
                 Ssc.25040.1.S1_at 
                 Serine/threonine- 
                 −3.75 
                 1.11 
                 1.06 
                 −2.45 
                 CHEK1 
                 UCN-01 (7-hydroxystaurosporine) 
               
               
                   
                 protein kinase Chk1 
               
               
                 Ssc.26379.1.S1_at 
                 Glutamate [NMDA] 
                 −1.32 
                 1.37 
                 1.03 
                 −2.59 
                 GRIN2C 
                 dextromethorphan/guaifenesin, 
               
               
                   
                 receptor subunit 
                   
                   
                   
                   
                   
                 morphine/dextromethorphan, neramexane, 
               
               
                   
                 epsilon 3 
                   
                   
                   
                   
                   
                 SPM 927, bicifadine, delucemine, CR 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2249, besonprodil, UK-240455, ketamine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 felbamate, memantine, orphenadrine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 cycloserine, N-(2-indanyl)glycinamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dextromethorphan, brompheniramine/ 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dextromethorphan/pseudoephedrine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 chlorpheniramine/dextromethorphan/ 
               
               
                   
                   
                   
                   
                   
                   
                   
                 phenylephrine, carbinoxamine/ 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dextromethorphan/pseudoephedrine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dextromethorphan/promethazine, 1- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aminocyclopropane-1-carboxylic acid 
               
               
                 Ssc.14488.1.S1_at 
                 Glutamate 
                 −1.04 
                 1.10 
                 1.02 
                 1.69 
                 FOLH1 
                 capromab pendetide 
               
               
                   
                 carboxypeptidase II 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 Upregulated gene targets at Days 21, 60 and 180 (relative to baseline) of PAH progression with available drugs 
               
             
          
           
               
                   
                   
                 Fold 
                 Fold 
                 Fold 
                 Fold 
                   
                   
               
               
                   
                   
                 Change 
                 Change 
                 Change 
                 Change 
               
               
                   
                   
                 D 7/ 
                 D 21/ 
                 D 60/ 
                 D 180/ 
                 Gene 
               
               
                 Probe ID 
                 Name 
                 Base 
                 Base 
                 Base 
                 Base 
                 Symbol 
                 Drugs 
               
               
                   
               
             
          
           
               
                 Ssc.23793.1.S1_at 
                 T-cell surface 
                 −3.27 
                 79.25 
                 93.34 
                 5.20 
                 CD2 
                 alefacept, siplizumab 
               
               
                   
                 antigen CD2 
               
               
                 SscAffx.20.1.S1_at 
                 T-cell surface 
                 −2.19 
                 14.07 
                 10.96 
                 3.62 
                 CD3G 
                 visilizumab, MT103 
               
               
                   
                 glycoprotein CD3 
               
               
                   
                 gamma chain 
               
               
                 Ssc.19532.1.S1_at 
                 Guanylate cyclase 
                 −4.28 
                 12.74 
                 3.04 
                 2.13 
                 GUCY1B3 
                 nitroglycerin, isosorbide-5-mononitrate, 
               
               
                   
                 soluble, beta-1 
                   
                   
                   
                   
                   
                 isosorbide dinitrate, nitroprusside, 
               
               
                   
                 chain 
                   
                   
                   
                   
                   
                 isosorbide dinitrate/hydralazine 
               
               
                 Ssc.7176.1.A1_at 
                 C-X-C chemokine 
                 3.74 
                 10.91 
                 8.15 
                 1.68 
                 CXCR4 
                 JM 3100 (1,1′-(1,4- 
               
               
                   
                 receptor type 4 
                   
                   
                   
                   
                   
                 phenylenebis(methylene))bis(1,4,8,11- 
               
               
                   
                 (CXC-R4) (CXCR-4) 
                   
                   
                   
                   
                   
                 tetraazacyclotetradecane)octahydrochloride 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dihydrate) 
               
               
                 Ssc.2714.1.S1_a_at 
                 Proto-oncogene 
                 −4.26 
                 9.56 
                 12.54 
                 3.93 
                 FYN 
                 dasatinib 
               
               
                   
                 tyrosine-protein 
               
               
                   
                 kinase FYN 
               
               
                 Ssc.10256.1.A1_at 
                 cAMP-specific 
                 −1.89 
                 6.74 
                 2.20 
                 2.44 
                 PDE4B 
                 dyphylline, nitroglycerin, arofylline, 
               
               
                   
                 3′,5′-cyclic 
                   
                   
                   
                   
                   
                 tetomilast, L 869298, aminophylline, 
               
               
                   
                 phosphodiesterase 
                   
                   
                   
                   
                   
                 anagrelide, cilomilast, milrinone, 
               
               
                   
                 4B 
                   
                   
                   
                   
                   
                 rolipram, dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, theophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline, caffeine 
               
               
                 Ssc.12937.1.S1_at 
                 Presenilin 1 (PS-1) 
                 −14.09 
                 6.21 
                 2.48 
                 3.79 
                 PSEN1 
                 (R)-flurbiprofen 
               
               
                   
                 (S182 protein). 
               
               
                 Ssc.15932.1.S1_at 
                 Integrin alpha-V 
                 −6.15 
                 5.79 
                 2.94 
                 3.14 
                 ITGAV 
                 abciximab, CNTO 95, EMD121974 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (Cilengitide) 
               
               
                 Ssc.26328.1.S1_at 
                 C-C chemokine 
                 −2.53 
                 5.61 
                 3.25 
                 1.29 
                 CCR5 
                 maraviroc, vicriviroc, SCH 351125 
               
               
                   
                 receptor type 5 
               
               
                   
                 (CCR5) 
               
               
                 Ssc.12845.1.S1_at 
                 Cell division 
                 −6.56 
                 5.40 
                 4.77 
                 5.13 
                 CDK6 
                 PD-0332991, flavopiridol 
               
               
                   
                 protein kinase 6 
               
               
                 Ssc.24528.1.S1_at 
                 Angiotensin- 
                 −1.61 
                 5.01 
                 2.33 
                 4.76 
                 ACE 
                 pentopril, perindoprilat, 
               
               
                   
                 converting enzyme 
                   
                   
                   
                   
                   
                 amlodipine/benazepril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 lisinopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benazepril, enalapril, perindopril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 captopril, enalapril/felodipine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/moexipril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 benazepril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 hydrochlorothiazide/quinapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fosinopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 captopril/hydrochlorothiazide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalapril/hydrochlorothiazide, ramipril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 moexipril, quinapril, lisinopril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 enalaprilat, trandolapril, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trandolapril/verapamil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 diltiazem/enalapril, fosinopril 
               
               
                 Ssc.7130.1.S1_at 
                 Phenylalanine-4- 
                 4.70 
                 4.71 
                 11.30 
                 1.48 
                 PAH 
                 (6R)-tetrahydrobiopterin 
               
               
                   
                 hydroxylase 
               
               
                 Ssc.7111.1.A1_at 
                 Ribonucleoside- 
                 −13.13 
                 4.08 
                 1.37 
                 1.67 
                 RRM2 
                 gemcitabine, triapine, hydroxyurea, 
               
               
                   
                 diphosphate 
                   
                   
                   
                   
                   
                 fludarabine phosphate 
               
               
                   
                 reductase M2 chain 
               
               
                   
                 (Ribonucleotide 
               
               
                   
                 reductase small 
               
               
                   
                 chain). 
               
               
                 Ssc.9272.1.S1_at 
                 Tumor-associated 
                 1.81 
                 3.94 
                 176.50 
                 2.07 
                 TACSTD1 
                 tucotuzumab celmoleukin 
               
               
                   
                 calcium signal 
               
               
                   
                 transducer 1 (EPCAM 
               
               
                   
                 antigen) 
               
               
                 Ssc.15886.1.S1_at 
                 Apopain (Caspase- 
                 −3.02 
                 3.64 
                 2.31 
                 2.29 
                 CASP3 
                 IDN-6556 
               
               
                   
                 3) (CASP-3) 
               
               
                 Ssc.21108.1.S1_at 
                 Complement C5 
                 −17.35 
                 3.21 
                 618.80 
                 9.28 
                 C5 
                 eculizumab 
               
               
                 Ssc.3040.1.S1_at 
                 Histone deacetylase 
                 −3.24 
                 2.79 
                 4.94 
                 4.72 
                 HDAC2 
                 tributyrin, PXD101, pyroxamide, 
               
               
                   
                 2 (HD2). 
                   
                   
                   
                   
                   
                 vorinostat, FR 901228 
               
               
                 Ssc.20685.1.S1_at 
                 Apoptosis regulator 
                 −2.22 
                 2.77 
                 2.58 
                 3.25 
                 BCL2 
                 oblimersen, (−)-gossypol 
               
               
                   
                 Bcl-2 
               
               
                 Ssc.818.1.S1_at 
                 RAF proto-oncogene 
                 −1.40 
                 2.56 
                 1.58 
                 1.98 
                 RAF1 
                 sorafenib 
               
               
                   
                 serine/threonine- 
               
               
                   
                 protein kinase 
               
               
                 Ssc.13186.1.S1_at 
                 Cell division 
                 −1.08 
                 2.38 
                 4.34 
                 1.24 
                 CDK7 
                 BMS-387032, flavopiridol 
               
               
                   
                 protein kinase 7 
               
               
                 Ssc.6418.1.S1_at 
                 Farnesyl- 
                 −1.25 
                 2.31 
                 1.33 
                 1.08 
                 FDFT1 
                 TAK-475, zoledronic acid 
               
               
                   
                 diphaosphate 
               
               
                   
                 farnesyltransferase 
               
               
                 Ssc.23505.1.S1_at 
                 Amine oxidase 
                 −1.86 
                 2.17 
                 1.08 
                 1.20 
                 MAOA 
                 ladostigil, 1-ethylphenoxathiin 10,10- 
               
               
                   
                 [flavin-containing] 
                   
                   
                   
                   
                   
                 dioxide, dextroamphetamine, procainamide, 
               
               
                   
                 A (Monoamine 
                   
                   
                   
                   
                   
                 tranylcypromine, phenelzine, 
               
               
                   
                 oxidase) (MAO-A). 
                   
                   
                   
                   
                   
                 isocarboxazid, benzphetamine, N-(2- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 indanyl)glycinamide 
               
               
                 Ssc.11302.1.S1_at 
                 Collagen alpha 
                 −1.80 
                 2.02 
                 2.06 
                 1.26 
                 COL3A1 
                 collagenase 
               
               
                   
                 1(III) chain 
               
               
                   
                 precursor. 
               
               
                 Ssc.18051.1.S1_at 
                 cGMP-inhibited 
                 −3.16 
                 1.96 
                 3.41 
                 2.32 
                 PDE3B 
                 dyphylline, nitroglycerin, medorinone, 
               
               
                   
                 3′,5′-cyclic 
                   
                   
                   
                   
                   
                 aminophylline, cilostazol, dipyridamole, 
               
               
                   
                 phosphodiesterase B 
                   
                   
                   
                   
                   
                 amrinone, tolbutamide, theophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pentoxifylline 
               
               
                 Ssc.23234.1.S1_at 
                 collagen, type 
                 −1.43 
                 1.66 
                 1.16 
                 1.76 
                 COL24A1 
                 collagenase 
               
               
                   
                 XXIV, alpha 1 
               
               
                 Ssc.5569.1.S1_at 
                 Thyroid hormone 
                 −10.22 
                 1.26 
                 1.26 
                 6.49 
                 THRA 
                 3,5-diiodothyropropionic acid, 
               
               
                   
                 receptor alpha 
                   
                   
                   
                   
                   
                 amiodarone, thyroxine, L-triiodothyronine 
               
               
                 Ssc.10360.1.S1_at 
                 B-Raf proto- 
                 −2.15 
                 1.26 
                 3.09 
                 1.36 
                 BRAF 
                 sorafenib 
               
               
                   
                 oncogene 
               
               
                   
                 serine/threonine- 
               
               
                   
                 protein kinase 
               
               
                 Ssc.5045.1.S1_at 
                 3-beta- 
                 −1.55 
                 1.24 
                 2.19 
                 2.08 
                 EBP 
                 SR 31747 
               
               
                   
                 hydroxysteroid- 
               
               
                   
                 delta(8),delta(7)- 
               
               
                   
                 isomerase 
               
               
                 Ssc.1498.1.S1_at 
                 Proteasome subunit 
                 −1.81 
                 1.19 
                 1.38 
                 5.94 
                 PSMB5 
                 bortezomib 
               
               
                   
                 beta type 5 
               
               
                 Ssc.28329.1.S1_at 
                 DNA polymerase beta 
                 1.14 
                 1.19 
                 1.07 
                 5.25 
                 POLB 
                 nelarabine, clofarabine, stavudine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 trifluridine, vidarabine, zalcitabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 entecavir 
               
               
                 Ssc.16823.1.S1_at 
                 P2Y purinoceptor 12 
                 1.38 
                 1.19 
                 1.41 
                 1.11 
                 P2RY12 
                 prasugrel, AZD 6140, clopidogrel 
               
               
                   
                 (P2Y12) (P2Y12 
               
               
                   
                 platelet ADP 
               
               
                   
                 receptor) 
               
               
                   
                 (P2Y(ADP)) 
               
               
                 Ssc.19691.1.S1_at 
                 Platelet-activating 
                 1.59 
                 1.16 
                 3.01 
                 1.47 
                 PLA2G7 
                 darapladib 
               
               
                   
                 factor 
               
               
                   
                 acetylhydrolase 
               
               
                 Ssc.19700.1.S1_at 
                 Serine/threonine 
                 1.11 
                 1.13 
                 1.34 
                 1.09 
                 PPP3CB 
                 ISAtx-247, tacrolimus, pimecrolimus, 
               
               
                   
                 protein phosphatase 
                   
                   
                   
                   
                   
                 cyclosporin A 
               
               
                   
                 2B catalytic 
               
               
                   
                 subunit, beta 
               
               
                 Ssc.14488.1.S1_at 
                 Glutamate 
                 −1.04 
                 1.10 
                 1.02 
                 1.69 
                 FOLH1 
                 capromab pendetide 
               
               
                   
                 carboxypeptidase II 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 10 
               
             
             
               
                   
               
               
                 Upregulated gene targets at both Days 7 and 21 (relative to baseline) of PAH progression with available drugs 
               
             
          
           
               
                   
                   
                 Fold 
                 Fold 
                 Fold 
                 Fold 
                   
                   
               
               
                   
                   
                 Change 
                 Change 
                 Change 
                 Change 
               
               
                   
                   
                 D 7/ 
                 D 21/ 
                 D 60/ 
                 D 180/ 
                 Gene 
               
               
                 Probe ID 
                 Name 
                 Base 
                 Base 
                 Base 
                 Base 
                 Symbol 
                 Drugs 
               
               
                   
               
             
          
           
               
                 Ssc.11381.1.S1_at 
                 Interferon-alpha/beta receptor 
                 10.45 
                 8.08 
                 2.61 
                 −1.30 
                 IFNAR1 
                 interferon beta-1a, 
               
               
                   
                 alpha chain 
                   
                   
                   
                   
                   
                 interferon alfa-2b, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfacon-1, PEG- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a/ribavirin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegintron, interferon beta- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 1b, IFNA2A 
               
               
                 Ssc.16186.1.S1_at 
                 T-cell surface glycoprotein 
                 9.00 
                 3.12 
                 2.12 
                 −5.66 
                 CD3E 
                 visilizumab, MT103, 
               
               
                   
                 CD3 epsilon chain 
                   
                   
                   
                   
                   
                 muromonab-CD3 
               
               
                 Ssc.19673.1.S1_at 
                 T-cell surface glycoprotein 
                 6.40 
                 2.70 
                 2.03 
                 −11.77 
                 CD3D 
                 visilizumab, MT103 
               
               
                   
                 CD3 delta chain 
               
               
                 Ssc.17155.1.A1_at 
                 heparanase; heparanase-1 
                 4.81 
                 5.38 
                 2.98 
                 −1.83 
                 HPSE 
                 heparanase inhibitor PI-88 
               
               
                 Ssc.7130.1.S1_at 
                 Phenylalanine-4-hydroxylase 
                 4.70 
                 4.71 
                 11.30 
                 1.48 
                 PAH 
                 (6R)-tetrahydrobiopterin 
               
               
                 Ssc.26351.1.S1_at 
                 cAMP-specific 3′,5′-cyclic 
                 4.67 
                 4.99 
                 3.61 
                 −1.15 
                 PDE4D 
                 dyphylline, nitroglycerin, 
               
               
                   
                 phosphodiesterase 4D 
                   
                   
                   
                   
                   
                 arofylline, tetomilast, L 
               
               
                   
                   
                   
                   
                   
                   
                   
                 869298, aminophylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 anagrelide, cilomilast, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 milrinone, rolipram, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dipyridamole, L-826,141, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 roflumilast, tolbutamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, pentoxifylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 caffeine 
               
               
                 Ssc.7176.1.A1_at 
                 C-X-C chemokine receptor 
                 3.74 
                 10.91 
                 8.15 
                 1.68 
                 CXCR4 
                 JM 3100 
               
               
                   
                 type 4 (CXC-R4) (CXCR-4) 
               
               
                 Ssc.15801.1.A1_at 
                 Protein kinase C, beta 
                 3.36 
                 6.36 
                 3.53 
                 −4.98 
                 PRKCB1 
                 enzastaurin, ruboxistaurin 
               
               
                 Ssc.12791.1.A1_at 
                 3-hydroxy-3-methylglutaryl- 
                 3.27 
                 2.77 
                 1.77 
                 −2.56 
                 HMGCR 
                 aspirin/pravastatin, 
               
               
                   
                 coenzyme A reductase 
                   
                   
                   
                   
                   
                 lovastatin/niacin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 ezetimibe/simvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 amlodipine/atorvastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 fluvastatin, cerivastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 atorvastatin, pravastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 simvastatin, lovastatin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 rosuvastatin 
               
               
                 Ssc.11147.1.S1_at 
                 Aldehyde dehydrogenase, 
                 3.18 
                 1.13 
                 2.00 
                 −1.68 
                 ALDH2 
                 disulfiram, chlorpropamide 
               
               
                   
                 mitochondrial 
               
               
                 Ssc.9565.1.S1_at 
                 Interferon-gamma receptor 
                 2.92 
                 1.63 
                 1.41 
                 −1.23 
                 IFNGR1 
                 interferon gamma-1b 
               
               
                   
                 alpha chain 
               
               
                 Ssc.3607.1.S1_at 
                 Interferon-alpha/beta receptor 
                 2.28 
                 4.65 
                 1.11 
                 −1.56 
                 IFNAR2 
                 interferon beta-1a, 
               
               
                   
                 beta 
                   
                   
                   
                   
                   
                 interferon alfa-2b, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfacon-1, PEG- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 interferon alfa-2a/ribavirin, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 pegintron, interferon beta- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 1b, IFNA2A 
               
               
                 Ssc.4756.1.A1_at 
                 Adenosine A3 receptor. 
                 2.15 
                 2.10 
                 1.88 
                 −1.81 
                 ADORA3 
                 adenosine, dyphylline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 aminophylline, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 theophylline, caffeine 
               
               
                 Ssc.10142.1.A1_at 
                 Dihydropyrimidine 
                 2.06 
                 2.17 
                 1.13 
                 −2.68 
                 DPYD 
                 eniluracil 
               
               
                   
                 dehydrogenase [NADP+] 
               
               
                 Ssc.15822.1.S1_at 
                 Coagulation factor V 
                 1.92 
                 3.76 
                 1.89 
                 −1.75 
                 F5 
                 drotrecogin alfa 
               
               
                 Ssc.14258.1.S1_at 
                 Amyloid beta A4 protein 
                 1.87 
                 3.33 
                 1.34 
                 −1.02 
                 APP 
                 AAB-001 
               
               
                   
                 precursor (APP) (ABPP) 
               
               
                 Ssc.15878.1.S1_at 
                 Serine/threonine protein 
                 1.85 
                 3.22 
                 3.62 
                 −1.49 
                 PPP3CA 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 phosphatase 2B catalytic 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                   
                 subunit, alpha 
               
               
                 Ssc.9272.1.S1_at 
                 Tumor-associated calcium 
                 1.81 
                 3.94 
                 176.50 
                 2.07 
                 TACSTD1 
                 tucotuzumab celmoleukin 
               
               
                   
                 signal transducer 1 (EPCAM 
               
               
                   
                 antigen) 
               
               
                 Ssc.19691.1.S1_at 
                 Platelet-activating factor 
                 1.59 
                 1.16 
                 3.01 
                 1.47 
                 PLA2G7 
                 darapladib 
               
               
                   
                 acetylhydrolase 
               
               
                 Ssc.30147.1.A1_at 
                 Fibroblast growth factor 
                 1.56 
                 1.13 
                 −1.05 
                 −1.18 
                 FGFR2 
                 palifermin 
               
               
                   
                 receptor 2 
               
               
                 Ssc.16823.1.S1_at 
                 P2Y purinoceptor 12 (P2Y12) 
                 1.38 
                 1.19 
                 1.41 
                 1.11 
                 P2RY12 
                 prasugrel, AZD 6140, 
               
               
                   
                 (P2Y12 platelet ADP receptor) 
                   
                   
                   
                   
                   
                 clopidogrel 
               
               
                 Ssc.15999.1.A1_at 
                 Vascular endothelial growth 
                 1.24 
                 1.24 
                 18.52 
                 −11.02 
                 KDR 
                 AEE 788, sunitinib, AZD 
               
               
                   
                 factor receptor 2 
                   
                   
                   
                   
                   
                 2171, pazopanib, XL647, CEP 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7055, BMS-582664, KRN-951, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vatalanib, sorafenib, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vandetanib, pegaptanib 
               
               
                 Ssc.17224.1.S1_at 
                 Toll-like receptor 8 
                 1.17 
                 6.49 
                 3.13 
                 −1.52 
                 TLR6 
                 resiquimod 
               
               
                 Ssc.7297.1.S1_at 
                 Amine oxidase 
                 1.16 
                 6.42 
                 7.02 
                 −1.13 
                 MAOB 
                 safinamide, ladostigil, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 rasagiline, selegiline, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dextroamphetamine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 procainamide, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 tranylcypromine, phenelzine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 isocarboxazid, benzphetamine 
               
               
                 Ssc.28329.1.S1_at 
                 DNA polymerase beta 
                 1.14 
                 1.19 
                 1.07 
                 5.25 
                 POLB 
                 nelarabine, clofarabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 stavudine, trifluridine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 vidarabine, zalcitabine, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 entecavir 
               
               
                 Ssc.19700.1.S1_at 
                 Serine/threonine protein 
                 1.11 
                 1.13 
                 1.34 
                 1.09 
                 PPP3CB 
                 ISAtx-247, tacrolimus, 
               
               
                   
                 phosphatase 2B catalytic 
                   
                   
                   
                   
                   
                 pimecrolimus, cyclosporin A 
               
               
                   
                 subunit, beta 
               
               
                 Ssc.8726.1.A1_at 
                 Amidophosphoribosyltransferase 
                 1.03 
                 1.24 
                 4.16 
                 −1.11 
                 PPAT 
                 6-mercaptopurine, 
               
               
                   
                 precursor 
                   
                   
                   
                   
                   
                 thioguanine, azathioprine 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
             
               
               
               
               
               
             
               
             
               
               
               
               
               
             
               
             
               
               
               
               
               
             
               
             
               
               
               
               
               
             
               
             
               
               
               
               
               
             
           
               
                 TABLE 11 
               
             
             
               
                   
               
               
                 Animal number, days after post-shunt PAH creation 
               
               
                 surgery, and pulmonary arterial pressure (PAP). 
               
             
          
           
               
                   
                 Animal 
                 Day 
                 PAP 
                 PAP mean 
               
               
                   
                   
               
             
          
           
               
                 Pig 19 Timecourse 
               
             
          
           
               
                   
                 P19 
                 Day 0 
                 28/1  
                 26 
               
               
                   
                 P19 
                 Day 10 
                 22/17 
                 19 
               
               
                   
                 P19 
                 Day 24 
                 76/29 
                 47 
               
               
                   
                 P19 
                 Day 59 
                 89/50 
                 58 
               
               
                   
                 P19 
                 Day 94 
                 70/18 
                 54 
               
             
          
           
               
                 Pig 20 Timecourse 
               
             
          
           
               
                   
                 P20 
                 Day 0 
                 20/11 
                 16 
               
               
                   
                 P20 
                 Day 6 
                 19/15 
                 16 
               
               
                   
                 P20 
                 Day 21 
                 20/15 
                 17 
               
               
                   
                 P20 
                 Day 55 
                 23/15 
                 19 
               
               
                   
                 P20 
                 Day 83 
                 62/17 
                 45 
               
               
                   
                 P20 
                 Day 104 
                 116/72  
                 104 
               
               
                   
                 P20 
                 Day 140 
                 92/40 
                 81 
               
             
          
           
               
                 Normal (Normal Pressure &amp; Flow) 
               
             
          
           
               
                   
                 P19 
                 Day 0 
                 28/1  
                 26 
               
               
                   
                 P20 
                 Day 0 
                 20/11 
                 16 
               
             
          
           
               
                 HFLP (High Flow Low Pressure) 
               
             
          
           
               
                   
                 P19 
                 Day 10 
                 22/17 
                 19 
               
               
                   
                 P20 
                 Day 6 
                 19/15 
                 16 
               
               
                   
                 P20 
                 Day 21 
                 20/15 
                 17 
               
               
                   
                 P20 
                 Day 55 
                 23/15 
                 19 
               
             
          
           
               
                 HFHP (High Flow High Pressure) 
               
             
          
           
               
                   
                 P19 
                 Day 24 
                 76/29 
                 47 
               
               
                   
                 P19 
                 Day 59 
                 89/50 
                 58 
               
               
                   
                 P19 
                 Day 94 
                 70/18 
                 54 
               
               
                   
                 P20 
                 Day 83 
                 62/17 
                 45 
               
               
                   
                 P20 
                 Day 104 
                 116/72  
                 104 
               
               
                   
                 P20 
                 Day 140 
                 92/40 
                 81 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 12 
               
             
             
               
                   
               
               
                 Significantly differently expressed downregulated 
               
               
                 microRNAs HFHP (High Flow High Pressure) vs. normal. 
               
               
                 Downregulated microRNA HFHP vs. Norm (p &lt; .05) 
               
             
          
           
               
                 Illumina ID 
                 Normal 
                 HFHP 
                 HFLP 
                 miRNA Symbol 
               
               
                   
               
             
          
           
               
                 ILMN_3167128 
                 32.58 
                 −2.36 
                 2.75 
                 solexa-603-1846 
               
               
                 ILMN_3167515 
                 4183.74 
                 42.62 
                 142.81 
                 hsa-miR-586 
               
               
                 ILMN_3168604 
                 31.83 
                 −2.01 
                 0.90 
                 hsa-miR-1201 
               
               
                 ILMN_3167691 
                 127.02 
                 1.76 
                 1358.98 
                 hsa-miR-33a 
               
               
                 ILMN_3167249 
                 229.25 
                 18.22 
                 511.84 
                 HS_56 
               
               
                 ILMN_3167753 
                 114.97 
                 14.32 
                 66.23 
                 hsa-miR-520d:9.1 
               
               
                 ILMN_3168215 
                 37.30 
                 8.98 
                 3110.35 
                 hsa-miR-521 
               
               
                 ILMN_3168168 
                 32.58 
                 1.72 
                 28.59 
                 hsa-miR-519a 
               
               
                 ILMN_3168054 
                 3916.21 
                 79.38 
                 14.02 
                 HS_134 
               
               
                 ILMN_3168235 
                 58.82 
                 6.34 
                 2.94 
                 HS_169 
               
               
                 ILMN_3168335 
                 15.54 
                 −2.85 
                 26.65 
                 HS_221 
               
               
                 ILMN_3167393 
                 90.38 
                 5.18 
                 5.54 
                 hsa-miR-496 
               
               
                 ILMN_3168678 
                 837.14 
                 14.23 
                 777.94 
                 hsa-miR-935 
               
               
                 ILMN_3167175 
                 8796.46 
                 1274.47 
                 88.95 
                 hsa-miR-542-5p 
               
               
                 ILMN_3168905 
                 92.30 
                 5.07 
                 33.55 
                 solexa-5620-151 
               
               
                 ILMN_3168648 
                 593.72 
                 46.29 
                 812.05 
                 hsa-miR-99a 
               
               
                 ILMN_3167761 
                 37.30 
                 16.59 
                 0.17 
                 hsa-miR-212 
               
               
                 ILMN_3168709 
                 1281.24 
                 218.10 
                 80.10 
                 hsa-let-7f-2 
               
               
                 ILMN_3168446 
                 8875.62 
                 343.70 
                 546.81 
                 hsa-miR-494 
               
               
                 ILMN_3168663 
                 31.00 
                 3.29 
                 18.23 
                 hsa-miR-1321 
               
               
                 ILMN_3168597 
                 99.25 
                 14.28 
                 43.96 
                 hsa-miR-219-2-3p 
               
               
                 ILMN_3166971 
                 1310.30 
                 311.18 
                 924.85 
                 hsa-miR-95 
               
               
                 ILMN_3167491 
                 3060.68 
                 925.46 
                 1647.50 
                 hsa-miR-128b:9.1 
               
               
                 ILMN_3168654 
                 740.78 
                 96.90 
                 957.01 
                 hsa-miR-33a 
               
               
                 ILMN_3167052 
                 370.00 
                 45.81 
                 234.11 
                 hsa-miR-495 
               
               
                 ILMN_3167337 
                 177.30 
                 43.83 
                 27.93 
                 hsa-miR-1229 
               
               
                 ILMN_3168827 
                 569.48 
                 117.37 
                 51.85 
                 hsa-miR-1205 
               
               
                 ILMN_3167328 
                 6444.52 
                 2162.76 
                 2119.65 
                 hsa-miR-524-3p 
               
               
                 ILMN_3167952 
                 8724.37 
                 2076.18 
                 926.06 
                 HS_150 
               
               
                 ILMN_3168798 
                 376.77 
                 151.44 
                 1348.57 
                 hsa-miR-135a 
               
               
                 ILMN_3168558 
                 211.48 
                 68.62 
                 28.31 
                 hsa-miR-483-5p 
               
               
                 ILMN_3168039 
                 9629.83 
                 3219.90 
                 7248.74 
                 hsa-miR-124a:9.1 
               
               
                 ILMN_3168755 
                 233.36 
                 82.45 
                 332.03 
                 hsa-miR-29b-1 
               
               
                 ILMN_3168540 
                 493.90 
                 161.33 
                 304.45 
                 hsa-miR-548c-5p 
               
               
                 ILMN_3168265 
                 11306.19 
                 5572.32 
                 6108.39 
                 hsa-miR-551a 
               
               
                 ILMN_3168481 
                 8687.78 
                 4563.60 
                 5504.04 
                 hsa-miR-377 
               
               
                 ILMN_3168882 
                 12023.57 
                 6677.06 
                 8627.69 
                 hsa-miR-1304 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 13 
               
             
             
               
                   
               
               
                 Significantly differently expressed upregulated 
               
               
                 microRNAs HFHP (High Flow High Pressure) vs. normal. 
               
               
                 Upregulated microRNA HFHP vs. Norm (p &lt; .05) 
               
             
          
           
               
                 Illumina ID 
                 Normal 
                 HFHP 
                 HFLP 
                 miRNA Symbol 
               
               
                   
               
             
          
           
               
                 ILMN_3168350 
                 −6.40 
                 2772.39 
                 12.69 
                 hsa-miR-520g 
               
               
                 ILMN_3168706 
                 −3.62 
                 1700.55 
                 8.11 
                 hsa-miR-331-5p 
               
               
                 ILMN_3167244 
                 −4.11 
                 1534.57 
                 −4.19 
                 hsa-miR-410 
               
               
                 ILMN_3168710 
                 −3.08 
                 1499.40 
                 2147.63 
                 hsa-let-7d 
               
               
                 ILMN_3168167 
                 −4.14 
                 1144.02 
                 558.78 
                 hsa-miR-187 
               
               
                 ILMN_3168672 
                 −4.20 
                 941.07 
                 162.41 
                 hsa-miR-16-2 
               
               
                 ILMN_3168870 
                 −8.25 
                 912.52 
                 8.99 
                 hsa-miR-130a 
               
               
                 ILMN_3168639 
                 −4.96 
                 728.32 
                 −3.51 
                 hsa-miR-548n 
               
               
                 ILMN_3168719 
                 −1.17 
                 380.69 
                 −2.12 
                 hsa-miR-127-5p 
               
               
                 ILMN_3168890 
                 −4.11 
                 343.04 
                 530.05 
                 solexa-2580-353 
               
               
                 ILMN_3168217 
                 −5.60 
                 304.34 
                 −1.25 
                 HS_206 
               
               
                 ILMN_3167088 
                 −5.06 
                 303.57 
                 −0.34 
                 hsa-miR-663 
               
               
                 ILMN_3168911 
                 −1.32 
                 235.62 
                 61.24 
                 solexa-7534-111 
               
               
                 ILMN_3168732 
                 −0.63 
                 216.74 
                 12.96 
                 hsa-let-7g 
               
               
                 ILMN_3167993 
                 −6.45 
                 192.76 
                 237.96 
                 HS_157 
               
               
                 ILMN_3167193 
                 −7.25 
                 151.36 
                 2130.07 
                 hsa-miR-610 
               
               
                 ILMN_3167879 
                 −4.09 
                 111.71 
                 11.99 
                 HS_251.1 
               
               
                 ILMN_3168031 
                 −4.54 
                 52.02 
                 15.76 
                 hsa-miR-519e 
               
               
                 ILMN_3168818 
                 −4.09 
                 20.75 
                 −0.83 
                 hsa-miR-1237 
               
               
                 ILMN_3168241 
                 −2.10 
                 18.57 
                 649.52 
                 hsa-miR-1185 
               
               
                 ILMN_3167470 
                 −4.18 
                 12.39 
                 7.90 
                 HS_151.1 
               
               
                 ILMN_3167512 
                 −1.69 
                 11.79 
                 9.99 
                 HS_135 
               
               
                 ILMN_3168895 
                 −2.86 
                 7.81 
                 0.75 
                 solexa-3126-285 
               
               
                 ILMN_3167158 
                 −0.63 
                 3.36 
                 739.08 
                 hsa-miR-30a 
               
               
                 ILMN_3168722 
                 1.26 
                 529.41 
                 430.69 
                 hsa-miR-192 
               
               
                 ILMN_3167039 
                 17.25 
                 1036.96 
                 883.92 
                 hsa-miR-568 
               
               
                 ILMN_3168680 
                 2.62 
                 148.59 
                 54.43 
                 hsa-miR-1203 
               
               
                 ILMN_3167223 
                 381.67 
                 5756.85 
                 4105.59 
                 hsa-miR-28-5p 
               
               
                 ILMN_3167361 
                 21.39 
                 259.94 
                 255.04 
                 HS_262.1 
               
               
                 ILMN_3167684 
                 11.78 
                 80.14 
                 21.38 
                 HS_170 
               
               
                 ILMN_3168760 
                 11.78 
                 80.09 
                 26.17 
                 hsa-miR-1273 
               
               
                 ILMN_3167275 
                 39.19 
                 146.84 
                 1900.87 
                 hsa-miR-602 
               
               
                 ILMN_3168240 
                 1613.60 
                 5725.95 
                 4943.62 
                 hsa-miR-374a 
               
               
                 ILMN_3168589 
                 597.66 
                 1739.42 
                 928.77 
                 hsa-miR-29a 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 14 
               
             
             
               
                   
               
               
                 Significantly differently expressed downregulated 
               
               
                 microRNAs HFLP (High Flow Low Pressure) vs. normal. 
               
               
                 Downregulated microRNA HFLP vs. Norm (p &lt; .05) 
               
             
          
           
               
                 Illumina ID 
                 Normal 
                 HFLP 
                 HFHP 
                 Gene Symbol 
               
               
                   
               
             
          
           
               
                 ILMN_3167209 
                 27.46 
                 −3.19 
                 1350.01 
                 HS_104 
               
               
                 ILMN_3168537 
                 38.77 
                 −0.76 
                 57.24 
                 hsa-miR-548a-5p 
               
               
                 ILMN_3167655 
                 351.30 
                 0.20 
                 74.35 
                 hsa-miR-556-5p 
               
               
                 ILMN_3168235 
                 58.82 
                 2.94 
                 6.34 
                 HS_169 
               
               
                 ILMN_3167800 
                 13.08 
                 −2.83 
                 1036.31 
                 HS_140 
               
               
                 ILMN_3167175 
                 8796.46 
                 88.95 
                 1274.47 
                 hsa-miR-542-5p 
               
               
                 ILMN_3168054 
                 3916.21 
                 14.02 
                 79.38 
                 HS_134 
               
               
                 ILMN_3167761 
                 37.30 
                 0.17 
                 16.59 
                 hsa-miR-212 
               
               
                 ILMN_3167509 
                 17.25 
                 −1.53 
                 17.72 
                 hsa-miR-363 
               
               
                 ILMN_3167707 
                 130.17 
                 1.49 
                 42.39 
                 HS_59 
               
               
                 ILMN_3167515 
                 4183.74 
                 142.81 
                 42.62 
                 hsa-miR-586 
               
               
                 ILMN_3168446 
                 8875.62 
                 546.81 
                 343.70 
                 hsa-miR-494 
               
               
                 ILMN_3168827 
                 569.48 
                 51.85 
                 117.37 
                 hsa-miR-1205 
               
               
                 ILMN_3168709 
                 1281.24 
                 80.10 
                 218.10 
                 hsa-let-7f-2 
               
               
                 ILMN_3168558 
                 211.48 
                 28.31 
                 68.62 
                 hsa-miR-483-5p 
               
               
                 ILMN_3167952 
                 8724.37 
                 926.06 
                 2076.18 
                 HS_150 
               
               
                 ILMN_3167337 
                 177.30 
                 27.93 
                 43.83 
                 hsa-miR-1229 
               
               
                 ILMN_3168305 
                 31.00 
                 5.36 
                 34.52 
                 HS_156 
               
               
                 ILMN_3168490 
                 67.94 
                 18.69 
                 106.29 
                 hsa-miR-619 
               
               
                 ILMN_3168573 
                 776.09 
                 190.47 
                 805.44 
                 hsa-miR-10b 
               
               
                 ILMN_3168586 
                 887.48 
                 304.35 
                 617.25 
                 hsa-miR-371-5p 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 15 
               
             
             
               
                   
               
               
                 Significantly differently expressed upregulated 
               
               
                 microRNAs HFLP (High Flow Low Pressure) vs. normal. 
               
               
                 Upregulated microRNA HFLP vs. Norm (p &lt; .05) 
               
             
          
           
               
                 Illumina ID 
                 Normal 
                 HFLP 
                 HFHP 
                 miRNA Symbol 
               
               
                   
               
             
          
           
               
                 ILMN_3168010 
                 −9.81 
                 2363.55 
                 689.66 
                 HS_70 
               
               
                 ILMN_3168710 
                 −3.08 
                 2147.63 
                 1499.40 
                 hsa-let-7d 
               
               
                 ILMN_3168167 
                 −4.14 
                 558.78 
                 1144.02 
                 hsa-miR-187 
               
               
                 ILMN_3168890 
                 −4.11 
                 530.05 
                 343.04 
                 solexa-2580-353 
               
               
                 ILMN_3167993 
                 −6.45 
                 237.96 
                 192.76 
                 HS_157 
               
               
                 ILMN_3168911 
                 −1.32 
                 61.24 
                 235.62 
                 solexa-7534-111 
               
               
                 ILMN_3168870 
                 −8.25 
                 8.99 
                 912.52 
                 hsa-miR-130a 
               
               
                 ILMN_3167512 
                 −1.69 
                 9.99 
                 11.79 
                 HS_135 
               
               
                 ILMN_3168722 
                 1.26 
                 430.69 
                 529.41 
                 hsa-miR-192 
               
               
                 ILMN_3167720 
                 2.62 
                 145.01 
                 147.62 
                 hsa-miR-154 
               
               
                 ILMN_3167062 
                 78.98 
                 2184.01 
                 1423.21 
                 hsa-miR-151:9.1 
               
               
                 ILMN_3168680 
                 2.62 
                 54.43 
                 148.59 
                 hsa-miR-1203 
               
               
                 ILMN_3167778 
                 24.39 
                 206.06 
                 81.33 
                 hsa-miR-525-3p 
               
               
                 ILMN_3167749 
                 37.30 
                 226.26 
                 272.25 
                 HS_199 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 16 
               
             
             
               
                   
               
               
                 Significantly differently expressed 
               
               
                 upregulated microRNAs HFHP vs. HFLP. 
               
               
                 Upregulated microRNA HFHP vs. HFLP (p &lt; .05) 
               
             
          
           
               
                 Illumina ID 
                 Normal 
                 HFHP 
                 HFLP 
                 miRNA Symbol 
               
               
                   
               
             
          
           
               
                 ILMN_3167244 
                 −4.11 
                 1534.57 
                 −4.19 
                 has-miR-410 
               
               
                 ILMN_3168639 
                 −4.96 
                 728.32 
                 −3.51 
                 has-miR-548n 
               
               
                 ILMN_3168537 
                 38.77 
                 57.24 
                 −0.76 
                 has-miR-548a-5p 
               
               
                 ILMN_3168613 
                 4.53 
                 18.13 
                 −0.99 
                 has-miR-185 
               
               
                 ILMN_3168047 
                 34.59 
                 10.25 
                 −4.94 
                 HS_3 
               
               
                 ILMN_3167440 
                 71.49 
                 −0.51 
                 −4.89 
                 HS_67 
               
               
                 ILMN_3168585 
                 45.00 
                 97.09 
                 2.43 
                 has-miR-1250 
               
               
                 ILMN_3168543 
                 140.56 
                 2778.92 
                 47.17 
                 has-miR-5481 
               
               
                 ILMN_3168221 
                 52.52 
                 216.12 
                 13.76 
                 has-miR-548c-3p 
               
               
                 ILMN_3167831 
                 31.83 
                 186.98 
                 12.94 
                 has-miR-520d-5p 
               
               
                 ILMN_3167105 
                 292.19 
                 174.71 
                 25.34 
                 has-miR-208b 
               
               
                 ILMN_3167313 
                 475.92 
                 793.85 
                 135.08 
                 HS_200 
               
               
                 ILMN_3168634 
                 892.54 
                 1830.74 
                 479.17 
                 has-miR-218-1 
               
               
                 ILMN_3168247 
                 390.00 
                 300.41 
                 111.54 
                 has-miR-643 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 17 
               
             
             
               
                   
               
               
                 Significantly differently expressed 
               
               
                 downregulated microRNAs HFHP vs. HFLP. 
               
               
                 Downregulated microRNA HFHP vs. HFLP (p &lt; .05) 
               
             
          
           
               
                 Illumina ID 
                 Normal 
                 HFHP 
                 HFLP 
                 miRNA Symbol 
               
               
                   
               
             
          
           
               
                 ILMN_3167778 
                 24.39 
                 81.33 
                 206.06 
                 hsa-miR-525-3p 
               
               
                 ILMN_3167052 
                 370.00 
                 45.81 
                 234.11 
                 hsa-miR-495 
               
               
                 ILMN_3168052 
                 176.33 
                 116.43 
                 480.71 
                 HS_250 
               
               
                 ILMN_3168863 
                 9.59 
                 1.11 
                 46.30 
                 hsa-miR-933 
               
               
                 ILMN_3168848 
                 13.53 
                 8.90 
                 475.98 
                 hsa-miR-1287 
               
               
                 ILMN_3168750 
                 784.33 
                 2850.15 
                 8118.48 
                 hsa-miR-1308 
               
               
                 ILMN_3168348 
                 10.81 
                 9.66 
                 553.87 
                 hsa-miR-133b 
               
               
                 ILMN_3166995 
                 1.97 
                 1.33 
                 254.82 
                 HS_215 
               
               
                 ILMN_3167545 
                 42.85 
                 10.92 
                 23.89 
                 HS_115 
               
               
                 ILMN_3168819 
                 756.53 
                 1345.27 
                 5334.48 
                 hsa-miR-151-5p 
               
               
                 ILMN_3167249 
                 229.25 
                 18.22 
                 511.84 
                 HS_56 
               
               
                 ILMN_3168010 
                 −9.81 
                 689.66 
                 2363.55 
                 HS_70 
               
               
                 ILMN_3168215 
                 37.30 
                 8.98 
                 3110.35 
                 hsa-miR-521

Technology Category: 8