Abstract:
Systems and methods provide a comprehensive high-throughput approach toward the sequential identification, prioritization, verification, and validation of etiologic factors in neuropsychiatric disorders, some of which can also be utilized as biomarkers for these illnesses. The systems and methods determine patterns of gene expression in various tissues from various samples under various experimental and non-experimental conditions, and uses the differences and similarities between the gene expression profiles observed under these conditions to delineate distinct gene expression profiles of risk and treatment of neuropsychiatric disorders.

Description:
RELATED APPLICATION 
     This application is a U.S. National Stage filing under 35 U.S.C. 371 from International Application No. PCT/2006/005533 filed 15 Feb. 2006, published in English as WO 2006/089062 A2 on 24 Aug. 2006, which claims the benefit of U.S. Provisional Application Ser. No. 60/653,217 filed 15 Feb. 2005, which applications and publication are incorporated herein by reference. 
    
    
     FIELD 
     The embodiments of the present invention relate to detection of biomarkers and the use of biomarkers. More specifically, the embodiments relate to systems and methods for detecting biomarkers for neuropsychiatric disorders and the use of selenium binding protein 1 (SELENBP1) as a biomarker. 
     BACKGROUND 
     Neuropsychiatric disorders may be etiologically complex and heterogeneous thereby making it difficult to identify risk factors for a particular neuropsychiatric disorder. Microarray techniques hold great promise for identifying risk factors for neuropsychiatric disorders such as schizophrenia (SZ) but have not yet generated widely reproducible results due to methodological differences between studies and the high risk of type I inferential errors. 
     Schizophrenia has a substantial genetic basis, but its biological underpinnings remain largely unknown. Early attempts to profile the expression of specific neurochemicals in blood and postmortem brain tissue detected several promising candidate risk factors for SZ that ultimately could not be substantiated. Subsequent progress in mapping the human genome increased the viability of candidate gene association studies. Most candidate genes have been targeted based on their expression within systems widely implicated in the disorder (e.g., dopamine and glutamate neurotransmitter systems), and this approach may be used for clarifying the nature of dysfunction within these recognized candidate pathways; however, it may not be optimal for identifying additional novel risk factors outside of these systems. 
     The advent of microarrays that can survey the entire expressed human genome has made it possible to simultaneously investigate the roles of several thousand genes in a disorder. Relative to traditional candidate gene studies predicated on existing disease models, microarray analysis is a less-constrained strategy that may foster the discovery of novel risk genes that otherwise would not come under study. Because gene expression can reflect both genetic and environmental influences, it may be particularly useful for identifying risk factors for a complex disorder such as SZ, which is thought to have a multifactorial polygenic etiology in which many genes and environmental factors interact. However, the simultaneous consideration of thousands of dependent variables also increases the likelihood of false-positive results. In short, microarrays hold great promise for identifying etiologic factors for SZ but run the risk of being too liberal and failing to provide replicable results. 
     Several groups have characterized gene expression profiles of SZ in postmortem tissue from the dorsolateral prefrontal cortex (DLPFC) of the brain, which has been consistently identified as dysfunctional in the illness. These studies have noted variable patterns of dysregulated gene expression in several domains, including G protein signaling, metabolism, mitochondrial function, myelination, and neuronal development. However, not all of these studies have reported significant alterations in each domain. Methodological differences, including ethnic and demographic disparities, alternative microarray platforms, and diverse methods of data analysis, as well as the high risk of false positives, have been cited as factors possibly contributing to this variability. 
     As a result, the gene expression profiles generated by existing methods are prone to the identification of false-positive results or risk factors that have little utility for diagnostic and predictive purposes. 
     SUMMARY 
     The embodiments of the present invention include systems and methods providing a comprehensive high-throughput approach toward the sequential identification, prioritization, verification, and validation of etiologic factors in neuropsychiatric disorders, some of which can also be utilized as biomarkers for these illnesses. The systems and methods determine patterns of gene expression in various tissues from various samples under various experimental and non-experimental conditions, and uses the differences and similarities between the gene expression profiles observed under these conditions to delineate distinct gene expression profiles of risk and treatment of neuropsychiatric disorders. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates the major components of a system for detecting biomarkers for neuropsychiatric disorders according to embodiments of the invention. 
         FIG. 2  is a flowchart illustrating an exemplary method for detecting biomarkers for neuropsychiatric disorders according to embodiments of the invention. 
         FIGS. 3A and 3B  illustrate the expression of SELENBP1 protein in DLPFC of a control subject and a patient diagnosed with schizophrenia. 
         FIGS. 4A and 4B  are graphs illustrating relationships between ontology terms identified by embodiments of the invention as overrepresented among genes differentially expressed in DLFPC in SZ. 
     
    
    
     DETAILED DESCRIPTION 
     In the following detailed description, reference is made to the accompanying drawings that form a part hereof, and in which is shown by way of illustration, specific embodiments in which the inventive subject matter may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice them, and it is to be understood that other embodiments may be utilized and that structural, logical, and electrical changes may be made without departing from the scope of the inventive subject matter. Such embodiments of the inventive subject matter may be referred to, individually and/or collectively, herein by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept if more than one is in fact disclosed. 
     The following description is, therefore, not to be taken in a limited sense, and the scope of the inventive subject matter is defined by the appended claims. 
     In the Figures, the same reference number is used throughout to refer to an identical component which appears in multiple Figures. Signals and connections may be referred to by the same reference number or label, and the actual meaning will be clear from its use in the context of the description. 
     The functions or algorithms described herein are implemented in hardware, and/or software in embodiments. The software comprises computer executable instructions stored on computer readable media such as memory or other types of storage devices. The term “computer readable media” is also used to represent software-transmitted carrier waves. Further, such functions correspond to modules, which are software, hardware, firmware, or any combination thereof. Multiple functions are performed in one or more modules as desired, and the embodiments described are merely examples. A digital signal processor, ASIC, microprocessor, or any other type of processor operating on a system, such as a personal computer, server, a router, or any other device capable of processing data including network interconnection devices executes the software. 
     Some embodiments implement the functions in two or more specific interconnected hardware modules or devices with related control and data signals communicated between and through the modules, or as portions of an application-specific integrated circuit. Thus, the example process flow is applicable to software, firmware, and hardware implementations. 
     Specific ranges, values, and embodiments provided below are for illustration purposes only and do not otherwise limit the scope of the invention, as defined by the claims. 
     As used herein, “selenium binding protein” includes polypeptides having at least 80%, e.g., at least 85%, 90%, 95%, or more amino acid sequence identity to sequences having NCBI Accession Nos. CAG33133, CAH70328, AAH32997, Q13228, P17563, AAH11202, NP003935, NP 033176, AAH74008, NP956864, NP543168, AAX43635, AAX31965, AAH56590, or AAH09084, and nucleic acid sequence encoding those polypeptides. In one embodiment, the selenium binding protein is selenium binding protein-1, e.g., human, rodent, for instance, rabbit, mouse, rat, mink or guinea pig, or nonhuman primate selenium binding protein-1. 
       FIG. 1  illustrates a system  100  for detecting potential biomarkers according to embodiments of the invention. In some embodiments, system  100  includes a statistical analysis system  120 , a comparator  140 , and an ontological identification system  160 . In some embodiments, statistical analysis system  120  is a computerized system that receives two input files each of which contain gene expression data, performs a statistical analysis of the two files, and generates an output file that contains gene data representing genes that are differentially expressed between the two input files. In general, one of the input files (e.g. file  102  or  112 ) contains gene expression data for a control group not having a neuropsychiatric disorder of interest and the other input file (e.g. file  104  or  114 ) contains gene expression data for a group that has been diagnosed with the neuropsychiatric disorder of interest. Further, the input files generally contain gene expression data obtained from the same source type in the control group and the sample group. For example, the gene expression data may be obtained from central nervous system tissue from the control group and the sample group or from blood samples obtained from the control group and the sample group. 
     Statistical analysis system  120  in some embodiments uses a model that assumes multiplicative rather than additive noise. Additionally, in some embodiments, statistical analysis system may be designed to eliminate statistically significant outliers. Additionally, the statistical model used in some embodiments assumes a uniform background level that is estimated from both mismatch and perfect-match probe intensities. As noted above, the output of statistical analysis system  120  is a file containing gene data for differentially expressed genes in the two input files. 
     In particular embodiments, statistical analysis system  120  is the CORGON biostatistical analysis system. Further details on the operation of the CORGON biostatistical analysis system is found in Sasik, R., Calvo, E. &amp; Corbeil, J. “Statistical Analysis of High-Density Oligonucleotide Arrays: A Multiplicative Noise Model”  Bioinformatics  18, 1633-1640 (2002), which is hereby incorporated by reference. 
     Additionally, some embodiments employ an algorithm in which identification of differentially expressed genes is based on their statistical significance beyond a threshold of P=0.05. In these embodiments, the P value of each gene is determined by two-tailed unadjusted permutation testing of 100,000 permutations of sample labels for each gene. For each permutation, the t statistic was calculated from log(expression) values, and the P value was estimated as the fraction of permutations for which the absolute value of the t statistic was greater than or equal to the absolute value of the unpermuted t statistic. In particular embodiments, an implementation of a FOCUS algorithm is used. Further details on the FOCUS algorithm may be found in Cole, S. W., Galic, Z. &amp; Zack, J. A. “Controlling false-negative errors in microarray differential expression analysis: a PRIM approach” (2003)  Bioinformatics  19, 1808-1816. 
     The application of the FOCUS algorithm in conjunction with the statistical model used in some embodiments described above may be useful in reducing the occurrence of Type I errors (false positives). 
     In operation, to determine biomarkers for a neuropsychiatric disorder of interest, statistical analysis system  120  is executed twice, once for each of two sample types, central nervous system tissue and blood. Thus in one execution, an input file  102  having gene expression data from central nervous system tissue samples obtained from a control group and a second input file  104  having gene expression data from central nervous system tissue samples obtained from individuals having the neuropsychiatric disorder are supplied to the statistical analysis system  120  to produce output file  132  having differentially expressed gene data in the brain tissue samples of the two input groups. In some embodiments, input files  102  and  112  may be cell intensity (CEL) files from the National Brain databank (NBD) web site. 
     Various forms of central nervous system tissue may be used. In some embodiments, DLPFC tissue may be used. In alternative embodiments, other tissue samples from other brain regions may be used to obtain gene expression data. In further alternative embodiments, cerebrospinal fluid may be used to obtain gene expression data. The embodiments of the invention are not limited to a particular central nervous system component. 
     In a second execution, statistical analysis system  120  receives an input file  112  having gene expression data from blood samples obtained from a control group not having the neuropsychiatric disorder and a second input file  114  having gene expression data from blood samples obtained from individuals having the neuropsychiatric disorder and produces an output file  134  having differentially expressed gene data in the blood samples of the two input groups. In some embodiments, the blood samples comprise peripheral blood cells. 
     Comparator  140  comprises software that compares two files having differentially expressed gene data and produces an output file  150  comprising a set of differentially expressed gene data that is common in both the brain tissue samples and the blood samples. In some embodiments, the comparator software may be a spreadsheet style program that sorts and orders entries in order to perform a comparison. An example of such a program is the Microsoft Excel spreadsheet program available from Microsoft Corporation of Redmond Wash. 
     Ontological identification system  160  receives the common set of differentially expressed gene data  150  and applies a bioinformatic analysis algorithm to identify the ontologies (biological processes, molecular functions, and cellular components) linked to those genes. In some embodiments, the identified genes are placed in an output  170  using standardized gene ontology (GO) terms, such as terms recognized by the GO Consortium and defined in “Gene Ontology: tool for the unification of biology. The Gene Ontology Consortium (2000) Nature Genet. 25: 25-29. In some embodiments, Ontological identification system  160  compares the list of differentially expressed genes identified by the statistical analysis system  120  and comparator  140  with the list of all genes on a microarray and determines which of the standardized GO terms are more frequently represented than would be expected by chance based on the genes represented in the entire microarray. Further, in some embodiments, ontological identification system  160  calculates conditional P values, which allows for the discovery of significant terms even if they are small in size. 
     In particular embodiments, ontological identification system  160  comprises an implementation of the MicroArray Data Characterization and Profiling (MADCAP) algorithm. Further details on the MADCAP algorithm may be found in Lozach, J., Sasik, R., Ogawa, S., Glass, C. K. “MADCAP: MicroArray Data Characterization And Profiling. A tool for profiling lists of genes with different expression patterns” (2003) in European Conference on Computational Biology (Institut National de la Recherche Agronomique, Paris), p. GE24, which is hereby incorporated by reference. 
     Further details on the operation of the system described above will be described below with reference to  FIG. 2 .  FIG. 2  illustrates flow diagrams of methods for determining biomarkers for neuropsychiatric disorders. The methods to be performed by the operating environment may include computer programs made up of computer-executable instructions. Describing the methods by reference to a flowchart enables one skilled in the art to develop such programs including such instructions to carry out the methods on suitable computers (the processor or processors of the computer executing the instructions from computer-readable media such as ROMs, RAMs, hard drives, CD-ROM, DVD-ROM, flash memory etc. The methods illustrated in  FIG. 2  are inclusive of acts that may be taken by an operating environment executing an example embodiment of the invention. In the discussion below, nonlimiting examples of the execution of the method may be provided in order to provide further description of the method. 
     The method begins by performing statistical analysis on gene expression data obtained from brain tissue from a control group and from brain tissue from a group having a neuropsychiatric disorder to obtain a first set of differentially expressed genes (block  202 ). In some embodiments, the brain tissue may be DLPFC, however the embodiments are not limited to a particular type of brain tissue. 
     In particular embodiments, gene expression data were obtained from cRNA microarrays of fresh-frozen postmortem DLPFC tissue samples (50 mg) from 19 SZ patients and 27 nonpsychiatric control subjects in the National Brain Databank (NBD) maintained by the Harvard Brain Tissue Resource Center (HBTRC). Patients and controls were closely matched on gender (68% vs. 70% male; P=0.887) and mean age (57 vs. 56 yrs; P=0.955), and DLPFC samples were very similar in laterality (58% vs. 52% right hemisphere; P=0.875), mean pH (6.4 vs. 6.4; P=0.981), and mean postmortem interval (21 vs. 20 h; P=0.739). Ascertainment and diagnosis of these subjects according to  Diagnostic and Statistical Manual of Mental Disorders  (DSM-IV) criteria, preparation of brain tissue, extraction, purification and hybridization of RNA, quantification of expression levels on cRNA microarrays, and quality-control procedures were all performed at the Harvard Brain Tissue Resource Center by standard methods. 
     At the Harvard Brain Tissue Resource Center, ≈50 mg of fresh frozen brain tissue was obtained from the DLPFC of each subject, and RNA was extracted using a Totally RNA Kit (Ambion, Austin, Tex.). RNA samples were then purified using an RNeasy Kit (Qiagen, Valencia, Calif.). RNA quality of each sample was verified before hybridization by examining the state of 28S and 18S ribosomal RNA by gel electrophoresis on an Agilent 2100 bioanalyzer (Agilent Technologies, Palo Alto, Calif.). RNA quality was very similar between samples from SZ patients and control subjects, as determined by several indices, including the mean 28S:18S RNA ratio (1.11 vs. 1.07; P=0.790) and the mean 3′:5′ ratio of the RNA transcripts of the housekeeping genes G3PDH (1.57 vs. 1.44; P=0.407) and ACTB (2.42 vs. 2.33; P=0.728). 
     Each purified and quality-assured RNA sample (8 μg) was reverse-transcribed by using a SuperScript II double-stranded cDNA synthesis kit (Invitrogen) to yield complimentary cDNAs, which were then transcribed and amplified in vitro with an Enzo-IVT kit (Affymetrix) to yield biotin-labeled cRNAs of all mRNAs present in the brain tissue sample. Samples of cRNA were then fragmented and hybridized to a GeneChip Human Genome U95A or U133A array (Affymetrix), which was stained in a GeneChip Fluidics Station 400 (Affymetrix) and scanned twice in a DNA Microarray Scanner 2500 (Agilent Technologies). Scans were then visually inspected for artifacts such as edge effects or scratches, which were detected in &lt;5% of samples. Samples affected with such artifacts were removed from the National Brain Databank (NBD) database. 
     Microarray suite 5.0 software (Affymetrix) was then used to assess the quality of the scans. For arrays with a rate of probe detection below 35%, the entire experimental procedure was repeated from the RNA extraction step forward. If the rate of probe detection was not improved above 35%, the gene expression data for that sample was not added to the NBD database. The rates of probe detection for the samples that we obtained from the NBD were essentially equivalent between the group of schizophrenia (SZ) patients and control subjects (45.8 vs. 45.9% present; P=0.913), and no sample had a rate of probe detection below 35%. 
     In some embodiments, expression levels of all genes identified as differentially expressed by the statistical analysis may then be examined in relation to antipsychotic and other medication use to determine whether the elevated frequency of such exposures among patients may account for group differences in gene expression. 
     The effects of anticonvulsant, antidepressant, and anxiolytic medications may be examined by comparing gene expression levels observed in treated and untreated groups with t tests for independent samples. Advancing beyond this scheme, antipsychotic medications may be evaluated in a more quantitative manner by converting daily dosages to a common metric (e.g., maximum effective dose) and examining correlations between this daily dose index and the expression level of each differentially expressed gene. Highly conservative family-wise corrections for multiple testing within each medication class may performed by using the Bonferroni correction 
     Additionally, a system executing the method performs statistical analysis on gene expression data obtained from blood samples from a control group and from blood samples from a group having the neuropsychiatric disorder to obtain a second set of differentially expressed genes (block  204 ). 
     In the execution of an embodiment, peripheral whole-blood samples (10 ml) were obtained from a separate set of 30 SZ patients and 24 nonpsychiatric control subjects. Patients and controls were of similar gender (40% vs. 58% male; P=0.180) but differed in mean age (34 vs. 42 yrs; P=0.014). All blood samples were collected into sterile violet-capped Vacutainer tubes (Becton Dickinson) containing K 3  EDTA, temporarily stored at 4° C., and processed within 6 h of collection. Ascertainment and diagnosis of these subjects according to  Diagnostic and Statistical Manual of Mental Disorders  (DSM-IV, ref. 12) criteria; collection and preparation of blood samples; separation and lysis of peripheral blood cells (PBCs); extraction, purification, and hybridization of RNA; quantification of expression levels on cRNA microarrays; and quality-control procedures were all performed by standard methods. 
     For some embodiments, each sample was processed by separating plasma, buffy coat, and red blood cell layers through centrifugation. Plasma was discarded, red blood cells were ruptured with lysis buffer, and each mixture was centrifuged again, yielding a pellet of white blood cells, which was briefly washed in lysis buffer. TRIzol (1 ml; Invitrogen) was then applied to extract mRNA, which was then purified and assessed for quality as described above for DLPFC samples. 
     Each purified and quality-assured RNA sample (5 μg) was prepared for microarray, hybridized to either a GeneChip Human Genome U133A or U133 Plus 2.0 array, and scanned once using an Affymetrix GeneChip Scanner and Affymetrix gcos software, Ver. 1.1.1, according to the manufacturer&#39;s published protocols (Affymetrix). 
     The gene expression data for the blood samples may then be analyzed by statistical analysis system  160  as described above an in a manner similar to that of the brain tissue samples. 
     The system also compares first and second sets of differentially expressed genes to identify a common set of differentially expressed genes (block  206 ). For example, the list of genes differentially expressed in the blood of these patients and controls may be compared with the list of genes previously identified as differentially expressed in the DLPFC of SZ patients and controls in the NBD. Medication effects on gene expression levels may be examined as outlined above for DLPFC samples, and the effect of age (which differed between patients and controls) may be evaluated by correlation as well. 
     Next, the system identifies gene ontologies from the common set of differentially expressed genes (block  208 ). In some embodiments, this may be performed by an ontological identification system  160 , including systems using the MADCAP algorithm. MADCAP compares the list of differentially expressed genes identified by statistical analysis system with the list of all genes on a microarray and determines which of the standardized GO terms are more frequently represented than would be expected by chance based on the genes represented in the entire microarray. 
     In some embodiments, genes may be classified according to the standardized ontology terms recognized by the Gene Ontology Consortium (GOC). The gene ontology (GO) classification system established and maintained by the GOC describes gene products in three domains, including Biological Process, Cellular Component, and Molecular Function. The grouping of genes based on ontological dimensions further increases the likelihood of identifying true-positive results for genes that exist within and influence the activity of a family of functionally related genes or an extended gene system that may change in synchrony in the disease state. 
     Ontological classifications and relationships of genes may be analyzed with the MicroArray Data Characterization and Profiling (MADCAP) algorithm, which is a tool for unsupervised statistical analysis of gene lists under the three separate GOs of the GOC. The algorithm finds all statistically significant ontology “terms” (of the &gt;18,000 terms recognized by the GOC) and the genes that represent them, and creates a graphical output of the ontology highlighting significant terms (e.g. see  FIGS. 4A and 4B ). The input into MADCAP consists of two lists of genes: a reference list and a selected list. The reference list typically contains all genes detected as expressed in the corgon-analyzed microarray dataset. The selected list of genes represents a smaller group of genes selected from the reference list according to some criterion, in some embodiments, the genes that were identified by the statistical analysis system as significantly differentially expressed in the DLPFC of SZ patients and control subjects. MADCAP then identifies which, if any, biological processes, cellular components, and molecular functions are significantly represented in the selected set of genes. Each gene can be linked to several ontology terms, either directly or through daughter GO terms. The reference gene list defines a reference ontology graph as determined by connections of individual genes to ontology terms and connections of terms to other terms. The selected genes define a subgraph of the reference graph. To identify the biological processes represented by the selected genes, MADCAP searches for terms linked to an unusually high number of selected genes. Specifically, starting from the root term of the subgraph and using the known structure of the graphs, we calculate the probability for each immediate daughter term (a value) that it be linked to as many or more selected genes than if the same number of genes was selected from the reference list at random. If the selected genes had been selected by a specific biological process (or processes) rather than at random, the process itself can be detected by an unusually large number of selected genes. 
     In some embodiments, the method includes verifying the set of differentially expressed gene data obtained from blood samples of the control group and the group having the neuropsychiatric disorder (block  210 ). 
     In the execution of a particular embodiment, the level of mRNA expression of the strongest candidate biomarker gene (SELENBP1, which was significantly up-regulated in both DLPFC and PBCs in SZ) was quantified in PBCs by RT-PCR. Total blood RNA isolated by the TRIzol method was reversed-transcribed into single-stranded cDNA by using a High-Capacity cDNA Archive Kit (Applied Biosystems) in a 100-μl reaction. Each sample of cDNA (2 ng) was then mixed with SYBR green master mix (Qiagen, Valencia, Calif.) and primers in a 20-μl reaction. Forward and reverse primers were designed by using PRIMERQUEST (Integrated DNA Technologies, Coralville, Iowa). PCR amplification was performed by using DNA Engine Opticon (MJ Research, Cambridge, Mass.). An automatically calculated melting point dissociation curve was examined to ensure specific PCR amplification and the lack of primer-dimer formation in each well. The comparative C t  equation (Applied Biosystems) was used to calculate relative fold changes between patient and control samples. Briefly, gene expression levels were represented as 2 t   −DΔC , where DΔC t ={[ΔC t (single sample)]−[mean ΔC t (control samples)]}, ΔC t ={[C t (target gene)]−[C t (ACTB)]}, and ACTB is the housekeeping gene coding for β actin. 
     In some embodiments, the method includes verifying the set of differentially expressed gene data obtained from the brain tissue of the control group and from the group having the neuropsychiatric disorder (block  212 ). In some embodiments, the verification include analyzing immunohistochemistry for the sample. 
     In the execution of a particular embodiment, paraffin wax-embedded DLPFC brain tissue sections (10 μm) were treated with citrate buffer, microwaved for 10 min, and exposed for 24 h at 4° C. to the mouse antiselenium binding protein monoclonal antibody (1:250 dilution; MBL International, Woburn, Mass.). Antibody was detected by using the mouse monoclonal Vectastain ABC kit and the 3,3′ diaminobenzidine substrate for peroxidase (Vector Laboratories). Sections were counterstained with hematoxylin, visualized on a Zeiss microscope, and analyzed by using IMAGE-PRO PLUS software (Media Cybernetics, Silver Spring, Md.). 
     Results of the Execution of Particular Embodiments 
     Gene Expression in DLPFC. Application of the CORGON and Focus algorithms described above to the brain gene expression data from 19 SZ patients and 27 control subjects in the NBD identified 177 genes that were differentially expressed in the DLPFC of the two groups. Of these, 111 genes were up-regulated, and 66 were down-regulated in SZ. The Affymetrix probe number, accession number, gene symbol, gene product, and chromosomal locus of each differentially expressed gene, as well as its fold-change difference in expression between SZ patients and control subjects and the corresponding P value, are provided in Table 4 below. Anticonvulsant-treated subjects showed significant down-regulation of six genes and up-regulation of one gene relative to untreated subjects, whereas anxiolytic treatment increased the expression of two genes and decreased the expression of two others. Antidepressant treatment influenced the expression of many more genes, with 10 showing significant upregulation and 7 showing significant down-regulation with treatment. Daily dosage of antipsychotic medication had a significant positive impact on the expression of 13 genes but was not significantly related to down-regulation of any genes. The significance of all of these medication effects was abolished by Bonferroni correction for multiple testing. 
     The 177 differentially expressed genes were then profiled by MicroArray Data Characterization and Profiling, and 25 were found to be linked to one or more overrepresented ontologies. Thirteen of the 25 genes represented six Biological Process GO terms.  FIG. 4A  is a graph showing the relationships between biological process ontology terms identified as overrepresented among genes differentially expressed in DLPFC in SZ. The most populated term within this ontology was Energy Pathways (P=0.007), which described the involvement of six genes shown in Table 1 below. In addition, 12 Molecular Function GO terms were represented by 18 genes.  FIG. 4B  is a graph showing the relationships between molecular function ontology terms identified as overrepresented among genes differentially expressed in DLPFC in SZ. The most populated term in this ontology was oxidoreductase activity (P=0.031), which described the function of seven genes and which are shown in Table 2 below. Three of these genes (NDUFA2, NDUFB5, and NDUFC1) were also classified as having NADH dehydrogenase activity. Genes representing terms in both the Biological Process and Molecular Function ontologies included ACOX1, COX7C, COX17, CNN3, NDUFA2, and NMT1, of which three genes (ACOX1, COX7C, and NDUFA2) had oxidoreductase activity within energy pathways. The remaining 152 differentially expressed genes were linked to GO terms that were not significantly overrepresented. 
     Gene Expression in PBCs. Application of the CORGON and Focus algorithms to the gene expression data from a separate sample of 30 SZ patients and 24 control subjects from Taiwan identified 123 genes that were differentially expressed in PBCs from the two groups. Of these, 67 genes were up-regulated and 56 down-regulated in SZ. The Affymetrix probe number, accession number, gene symbol, gene product, and chromosomal locus of each differentially expressed gene, as well as its fold-change difference in expression between SZ patients and control subjects and the corresponding P value, are provided in Table 5 below. Eight genes increased and 10 genes decreased significantly in expression level with age. Anticonvulsant-treated subjects differed from untreated subjects in the expression of only one gene, which was up-regulated; however, antidepressant treatment was associated with significant up-regulation of 15 genes and significant down-regulation of two others. The effects of age and these classes of medication did not remain significant after correction for multiple testing. Remarkably, anxiolytic treatment was associated with significant upregulation of 34 genes and down-regulation of another 40. Differential expression of 12 of these genes [including CSDA, EPB42, FBXO9, FKBP8, GSK3A HBA1 (two transcripts), HBA2, HBB (two transcripts), HLA-B, and UBB) remained significant after correcting for multiple testing. Daily dosage of antipsychotic medication was linearly related to the expression of only one gene (G0S2), which also remained statistically significant after corrections for multiple testing were applied. 
     Comparing the list of 123 genes differentially expressed in PBCs with that obtained from DLPFC identified six genes common to both. These six genes are detailed in Table 3 below. BTG1, HRNPA3, and SFRS1 were significantly up-regulated in the DLPFC in SZ but significantly down-regulated in PBCs from the other sample of SZ patients; the reverse pattern of differential expression was observed for GSK3A, which was the only one of these six genes to show a significant relationship to psychotropic medication (i.e., anticonvulsant) use. In contrast, SELENBP1 was significantly up-regulated in both tissues from the two samples of SZ patients. HLA-DRB1 was significantly downregulated in both DLPFC and PBCs in SZ; however, different probe sets (corresponding to different transcripts of the same gene) were associated with the illness in the two tissues. 
     SELENBP1 was identified as the strongest candidate biomarker among all genes differentially expressed in SZ, because it was the only gene for which identical probe sets indicated significant differential expression in a similar direction in both brain and blood in SZ. This significant up-regulation was substantiated by RT-PCR in PBCs from a randomly selected subset of the same SZ patients (n=21) and controls (n=18) that were profiled by microarray analysis. A highly significant (P=0.003) 2.2-fold increase in SELENBP1 was observed in PBCs of SZ patients by RT-PCR, which closely corresponded to the significant 2.0-fold up-regulation of the gene observed by microarray. 
     Protein Expression in DLPFC. Granular cytoplasmic staining of SELENBP1 protein was observed in a proportion of neurons and glia in DLPFC tissue from each of the four control subjects and four SZ patients. A representative example of the antibody-staining pattern observed in controls is shown in  FIG. 3A , whereas a representative example of the antibody-staining pattern observed in patients is shown in  FIG. 3B . Arrows  310  and  320  indicate antibody staining of cytoplasm in different cell types, with arrow  310  indicating glia and arrow  320  indicating neurons. Compared with control tissue, the intensity and ratio of glial/neuronal SELENBP1 antibody staining was noticeably increased in DLPFC tissue from at least three of the four SZ patients. The enhanced intraglial staining of SELENBP1 antibody in samples from SZ patients was most notable in a perinuclear rim of increased expression. No staining was observed in any cell when the primary antibody was omitted. 
     Analysis of Results 
     In some embodiments, a protocol for analysis and interpretation of gene expression microarray data includes using the CORGON and Focus algorithms to limit type I errors and MicroArray Data Characterization and Profiling to identify the ontologies represented by differentially expressed genes. Application of embodiments to gene expression data from DLPFC in SZ identified 177 genes, 6 biological processes, and 12 molecular functions that may be considered as high-priority targets for gene association analyses and hypothesis-driven functional studies. Twenty-eight of these genes also code to chromosomal loci strongly implicated in SZ by linkage analysis (Table 4) and are thus particularly attractive candidates. These include four genes (ACOX1, NDUFA2, SUCLG1, and TAPBP) that were also linked to significantly overrepresented GO terms, and SFRS1 and HLA-DRB1, which were differentially expressed in both DLPFC and PBCs in SZ. These genes provide reference points for the fine-mapping and positional cloning of putative SZ risk loci. 
     Application of embodiments of the invention resulted in GO terms overrepresented in DLPFC in the present study that were generally related to neurotransmitter systems not typically implicated in SZ (e.g., GABA receptor activity), neuronal processes not specific to a given neurotransmitter system (e.g., regulation of action potential), or biological processes not specific to the nervous system (e.g., energy pathways). More precisely, genes related to energy metabolism were predominant among those differentially expressed in DLPFC in SZ. Furthermore, at least four of the genes implicated in the results described above are involved in electron transfer, and three of these are also part of the NADH dehydrogenase complex located in the inner mitochondrial membrane. These data suggest that dysfunction within particular pathways or processes, but perhaps not necessarily in specific genes, might be important in the etiology of SZ. 
     Additionally, each of the 177 genes differentially expressed in DLPFC of SZ patients is a promising candidate risk gene. Also, the 123 genes differentially expressed in PBCs from such patients can be considered putative biomarkers for the illness. Six of the putative biomarker genes identified above in PBCs were also differentially expressed in the brain in SZ. Among these were BTG1, which regulates cell proliferation, and three genes (GSK3A, HNRPA3, and SFRS1) that regulate RNA splicing or transcription. The genes noted above may be considered secondary candidate SZ biomarkers to SELENBP1 and HLADRB1, which showed altered expression in the same direction in both DLPFC and PBCs (up- and down-regulation, respectively). Furthermore, HLA-DRB1 maps to the MHC region on chromosome 6p21.3, which is a prime candidate locus for SZ (22), and SELENBP1 maps to chromosome 1q21-22, a locus that has been strongly linked to SZ in some but not most genome-wide linkage studies. 
     Additionally, the utility of SELENBP1 as a potential peripheral biomarker was substantiated by RT-PCR verification of its up-regulation in PBCs. The altered levels of SELENBP1 transcripts measured in DLPFC and PBCs also translated into observable consequences at the functional level, because analyses suggests that expression of SELENBP1 protein was denser in glia and less dense in neurons of the DLPFC in SZ. 
     Thus various embodiments of the invention use SELENBP1 in various methods. For example, in some embodiments, a method to diagnose a neuropsychiatric disorder comprises detecting or determining the amount or level of selenium binding protein expression in cells in a physiological sample of a first mammal. An increase in the amount or level of selenium binding protein expression in the cells of the first mammal relative to the amount of level of selenium binding protein expression in cells of a mammal not having a psychotic mental disorder is indicative of a psychotic mental disorder in the first mammal. The physiological sample may be blood, including peripheral blood cells. 
     In further embodiments, a method to determine a mammal at risk of a neuropsychiatric disorder includes comparing the amount or level of selenium binding protein expression in cells in a physiological sample from a first mammal to the amount or level of selenium binding protein expression in cells from the first mammal at an earlier point in time or to the amount or level of selenium binding protein expression in cells of a mammal not having a neuropsychiatric disorder. An increase in the amount or level of selenium binding protein expression in the cells of the first mammal over time or relative to the mammal not having a neuropsychiatric disorder is indicative that the first mammal is at risk of a neuropsychiatric disorder. The physiological sample may be blood, including peripheral blood cells. 
     In still further embodiments, a method to determine the risk of progression of a neuropsychiatric disorder in a mammal includes comparing the amount or level of selenium binding protein expression in cells in a physiological sample from a mammal having a neuropsychiatric disorder to the amount or level of selenium binding protein expression in cells from the mammal at an earlier point in time. An increase in the amount or level of selenium binding protein expression over time is indicative that the mammal is at risk of progression of the neuropsychiatric disorder. The physiological sample may be blood, including peripheral blood cells. 
     In yet further embodiments, a method to determine whether an agent inhibits selenium binding protein expression in cells of a mammal includes
         a) administering an agent to a mammal; and   b) detecting or determining whether the agent inhibits selenium binding protein expression in cells in a physiological sample of the mammal.       

     In further embodiments, a method to determine whether an agent inhibits or treats a neuropsychiatric disorder includes:
         a) administering an agent to a mammal having a neuropsychiatric disorder; and   b) detecting or determining whether the agent inhibits selenium binding protein expression in cells in a physiological sample of the mammal. A decrease in the amount or level of selenium binding protein expression in the cells is indicative of an agent useful to inhibit or treat the neuropsychiatric disorder.       

     The embodiments described above provide systems and methods for analysis of gene expression microarray data to detect potential biomarkers for a neuropsychiatric disorder and for using biomarkers detected as a result of the analysis. Application of the embodiments resulted in 177 putative SZ risk genes in DLPFC, 28 of which map to chromosomal loci linked to the disorder; delineated 6 biological processes and 12 molecular functions that may be particularly disrupted in the illness; identified 123 putative SZ biomarkers in PBCs, 6 of which had corresponding differential expression in DLPFC; verified the up-regulation of the strongest candidate SZ biomarker (SELENBP1) in PBCs; and demonstrated an altered pattern of expression of SELENBP1 protein in DLPFC in SZ. While the discussion above has focused on SZ, those of skill in the art will appreciate that the systems and methods described above may be applied to other brain regions (e.g., both implicated and nonimplicated structures, to identify ubiquitous and region-specific changes) and populations (e.g., bipolar disorder patients, to establish disease-specific changes) in order to facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for SZ and other neuropsychiatric disorders. 
     In the foregoing Detailed Description, various features are grouped together in a single embodiment for the purpose of streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed embodiments have more features than are expressly recited in each claim. Thus the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate embodiment. 
     The foregoing descriptions of specific embodiments of the present invention have been presented for purposes of illustration and description. The embodiments presented are not intended to be exhaustive or to limit the invention to the particular forms disclosed. It should be understood that one of ordinary skill in the art can recognize that the teachings of the detailed description allow for a variety of modifications and variations that are not disclosed herein but are nevertheless within the scope of the present invention. Accordingly, it is intended that the scope of the present invention be defined by the appended claims and their equivalents, rather than by the description of the embodiments. 
     The Abstract is provided to comply with 37 C.F.R. §1.72(b) to allow the reader to quickly ascertain the nature and gist of the technical disclosure. The Abstract is submitted with the understanding that it will not be used to limit the scope of the claims. 
     
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Biological Process ontology terms overrepresented by genes differentially expressed in DLPFC in SZ 
               
             
          
           
               
                 Ontology Term 
                 p 
                 Gene Symbol 
                 Gene Product 
                 Gene Fold-Change (p) in SZ 
               
               
                   
               
               
                 ATP-Dependent Proteolysis 
                 0.022 
                 CRBN 
                 cereblon 
                 1.08 (0.01660) 
               
               
                 Circulation 
                 0.023 
                 LPL 
                 lipoprotein lipase 
                 1.28 (0.02680) 
               
               
                   
                   
                 RYR2 
                 ryanodine receptor 2 (cardiac) 
                 1.14 (0.01030) 
               
               
                   
                   
                 SRI 
                 sorcin 
                 1.20 (0.02480) 
               
               
                 Energy Pathways 
                 0.007 
                 ACOX1 
                 acyl-Coenzyme A oxidase 1, palmitoyl 
                 1.20 (0.00480) 
               
               
                   
                   
                 COX17 
                 COX17 homolog, cytochrome c oxidase assembly protein (yeast) 
                 1.10 (0.01780) 
               
               
                   
                   
                 COX7C 
                 cytochrome c oxidase subunit VIIc 
                 1.07 (0.04030) 
               
               
                   
                   
                 GLP1R 
                 glucagon-like peptide 1 receptor 
                 −1.09 (0.03080)  
               
               
                   
                   
                 NDUFA2 
                 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8 kDa 
                 1.09 (0.02260) 
               
               
                   
                   
                 SUCLG1 
                 succinate-CoA ligase, GDP-forming, alpha subunit 
                 1.06 (0.02870) 
               
               
                 Muscle Contraction 
                 0.041 
                 CNN3 
                 calponin 3, acidic 
                 1.37 (0.01660) 
               
               
                   
                   
                 RYR2 
                 ryanodine receptor 2 (cardiac) 
                 1.14 (0.01030) 
               
               
                   
                   
                 SRI 
                 sorcin 
                 1.20 (0.02480) 
               
               
                   
                   
                 SSPN 
                 sarcospan (Kras oncogene-associated gene) 
                 1.21 (0.04060) 
               
               
                 Protein-Lipoylation 
                 0.004 
                 NMT1 
                 N-myristoyltransferase 
                 1.09 (0.00980) 
               
               
                 Regulation of Action 
                 0.013 
                 SRI 
                 sorcin 
                 1.20 (0.02480) 
               
               
                 Potential 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Molecular Function ontology terms overrepresented by genes differentially expressed in DLPFC in SZ 
               
             
          
           
               
                   
                   
                   
                   
                 Gene Fold-Change 
               
               
                 Ontology Term 
                 p 
                 Gene Symbol 
                 Gene Product 
                 (p) in SZ 
               
               
                   
               
               
                 Beta-Catenin Binding 
                 0.041 
                 APC 
                 adenomatosis polyposis coli 
                 1.14 (0.02510) 
               
               
                 Calpain Activity 
                 0.009 
                 CAPN1 
                 calpain 1, (mu/l) large subunit 
                 −1.10 (0.02210)  
               
               
                   
                   
                 CAPNS1 
                 calpain, small subunit 1 
                 −1.10 (0.01740)  
               
               
                 Copper Ion Transporter Activity 
                 0.016 
                 COX17 
                 COX17 homolog, cytochrome c oxidase assembly protein (yeast) 
                 1.10 (0.01780) 
               
               
                 Electron Donor Activity 
                 0.027 
                 ACOX1 
                 acyl-Coenzyme A oxidase 1, palmitoyl 
                 1.20 (0.00480) 
               
               
                 GABA Receptor Activity 
                 0.012 
                 GABRA2 
                 gamma-aminobutyric acid (GABA) A receptor, alpha 2 
                 1.22 (0.01050) 
               
               
                   
                   
                 GABRB1 
                 gamma-aminobutyric acid (GABA) A receptor, beta 1 
                 1.16 (0.04360) 
               
               
                 Glycylpeptide 
                 0.048 
                 NMT1 
                 N-myristoyltransferase 
                 1.09 (0.00980) 
               
               
                 N-Tetradecanoyltransferase 
               
               
                 Activity 
               
               
                 MHC Protein Binding 
                 0.048 
                 TAPBP 
                 TAP binding protein (tapasin) 
                 −1.09 (0.02930)  
               
               
                 NADH Dehydrogenase Activity 
                 0.019 
                 NDUFA2 
                 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8 kDa 
                 1.09 (0.02260) 
               
               
                   
                   
                 NDUFB5 
                 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16 kDa 
                 1.09 (0.02910) 
               
               
                   
                   
                 NDUFC1 
                 NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 1, 6 kDa 
                 1.07 (0.00900) 
               
               
                 Oxidoreductase Activity 
                 0.031 
                 ACOX1 
                 acyl-Coenzyme A oxidase 1, palmitoyl 
                 1.20 (0.00480) 
               
               
                   
                   
                 COX7C 
                 cytochrome c oxidase subunit VIIc 
                 1.07 (0.04030) 
               
               
                   
                   
                 HSD17B12 
                 hydroxysteroid (17-beta) dehydrogenase 12 
                 1.11 (0.03900) 
               
               
                   
                   
                 NDUFA2 
                 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8 kDa 
                 1.09 (0.02260) 
               
               
                   
                   
                 NDUFB5 
                 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16 kDa 
                 1.09 (0.02910) 
               
               
                   
                   
                 NDUFC1 
                 NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 1, 6 kDa 
                 1.07 (0.00900) 
               
               
                   
                   
                 P4HA1 
                 procollagen-proline, 2-oxoglutarate 4-dioxygenase, alpha polypeptide I 
                 1.12 (0.03640) 
               
               
                 Peroxisome Targeting Signal 
                 0.031 
                 PEX5 
                 peroxisomal biogenesis factor 5 
                 −1.12 (0.00890)  
               
               
                 Receptor Activity 
               
               
                 Phosphoserine Phosphatase 
                 0.009 
                 PSPHL 
                 phosphoserine phosphatase-like 
                 −2.14 (0.04420)  
               
               
                 Activity 
               
               
                 Troponin C Binding 
                 0.030 
                 CNN3 
                 calponin 3, acidic 
                 1.37 (0.01660) 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Six genes differentially expressed in both DLPFC and PBCs in SZ 
               
             
          
           
               
                 Affymetrix 
                 Accession 
                 Gene 
                 Gene 
                 Chromosomal 
                 Fold-Change (p) in SZ 
               
             
          
           
               
                 Probe Number 
                 Number 
                 Symbol 
                 Product 
                 Locus 
                 DLPFC 
                 PBCs 
               
               
                   
               
               
                 200920_s_at 
                 AL535380 
                 BTG1 
                 B-cell translocation gene 1, anti-proliferative 
                 12q22 
                 1.14 (0.04020) 
                 −1.36 (0.00008) 
               
               
                 202210_x_at 
                 NM_019884 
                 GSK3A 
                 glycogen synthase kinase 3 alpha 
                 19q13.2 
                 −1.09 (0.02490)   
                   1.59 (0.00044) 
               
               
                 209728_at 
                 BC005312 
                 HLA-DRB1 
                 major histocompatibility complex, class II, 
                 6p21.3 
                 −1.17 (0.04220)   
                 NS* 
               
               
                   
                   
                   
                 DR beta 1 
               
               
                 209312_x_at 
                 U65585 
                 ″ 
                 major histocompatibility complex, class II, 
                 ″ 
                 NS* 
                 −1.27 (0.00007) 
               
               
                   
                   
                   
                 DR beta 1 
               
               
                 215193_x_at 
                 AJ297586 
                 ″ 
                 major histocompatibility complex, class II, 
                 ″ 
                 NS* 
                 −1.33 (0.00006) 
               
               
                   
                   
                   
                 DR beta 1 
               
               
                 211929_at 
                 AA527502 
                 HNRPA3 
                 heterogeneous nuclear ribonucleoprotein A3 
                 2q31.2 
                 1.15 (0.01410) 
                 −2.12 (0.00004) 
               
               
                 214433_s_at 
                 NM_003944 
                 SELENBP1 
                 selenium binding protein 1 
                 1q21-q22 
                 1.16 (0.04510) 
                   1.95 (0.00093) 
               
               
                 211784_s_at 
                 BC006181 
                 SFRS1 
                 splicing factor, arginine/serine-rich 1 
                 17q21.3-q22 
                 1.12 (0.02460) 
                 −1.71 (0.00005) 
               
               
                   
                   
                   
                 (splicing factor 2, alternate splicing factor) 
               
               
                   
               
               
                 *NS probe was not differentially expressed on the microarray used to profile the indicated tissue 
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Genes differentially expressed in DLPFC in SZ 
               
             
          
           
               
                   
                   
                   
                   
                   
                 Fold- 
                   
               
               
                 Affymetrix 
                 Accession 
                 Gene 
                 Gene 
                 Chromosomal 
                 Change 
               
               
                 Probe Number 
                 Number 
                 Symbol 
                 Product 
                 Locus* 
                 in SZ 
                 p 
               
               
                   
               
             
          
           
               
                 210764_s_at 
                 AF003114 
                 CYR61 
                 cysteine-rich, angiogenic inducer, 61 
                 1p31-p22 
                 1.39 
                 0.02990 
               
               
                 201445_at 
                 NM_001839 
                 CNN3 
                 calponin 3, acidic 
                 1p22-p21 
                 1.37 
                 0.01660 
               
               
                 208859_s_at 
                 AI650257 
                 ATRX 
                 alpha thalassemia/mental retardation syndrome X-linked 
                 Xq13.1-q21.1 
                 1.36 
                 0.00980 
               
               
                   
                   
                   
                 (RAD54 homolog,  S. cerevisiae ) 
               
               
                 215338_s_at 
                 AI688640 
                 NKTR 
                 natural killer-tumor recognition sequence 
                 3p23-p21 
                 1.33 
                 0.00280 
               
               
                 216563_at 
                 X80821 
                 ANKRD12 
                 ankyrin repeat domain 12 
                 18p11.22 
                 1.32 
                 0.01470 
               
               
                 216609_at 
                 AF065241 
                 TXN 
                 thioredoxin 
                 9q31 
                 1.32 
                 0.01980 
               
               
                 208993_s_at 
                 AW340788 
                 PPIG 
                 peptidyl-prolyl isomerase G (cyclophilin G) 
                 2q31.1 
                 1.30 
                 0.03260 
               
               
                 209655_s_at 
                 AI803181 
                 TM4SF10 
                 transmembrane 4 superfamily member 10 
                 Xp11.4 
                 1.30 
                 0.01260 
               
               
                 203548_s_at 
                 BF672975 
                 LPL 
                 lipoprotein lipase 
                 8p22* 
                 1.28 
                 0.02680 
               
               
                 217820_s_at 
                 NM_018212 
                 ENAH 
                 enabled homolog ( Drosophila ) 
                 1q42.12 
                 1.28 
                 0.00620 
               
               
                 211997_x_at 
                 NM_005324 
                 H3F3B 
                 H3 histone, family 3B (H3.3B) 
                 17q25 
                 1.26 
                 0.00280 
               
               
                 214212_x_at 
                 AI928241 
                 PLEKHC1 
                 pleckstrin homology domain containing, family C 
                 14q22.1 
                 1.26 
                 0.04640 
               
               
                   
                   
                   
                 (with FERM domain) member 1 
               
               
                 218930_s_at 
                 NM_018374 
                 FLJ11273 
                 hypothetical protein FLJ11273 
                 7p21.3 
                 1.26 
                 0.01520 
               
               
                 202619_s_at 
                 AI754404 
                 PLOD2 
                 procollagen-lysine, 2-oxoglutarate 5-dioxygenase 
                 3q23-q24 
                 1.25 
                 0.02280 
               
               
                   
                   
                   
                 (lysine hydroxylase) 2 
               
               
                 202412_s_at 
                 AW499935 
                 USP1 
                 ubiquitin specific protease 1 
                 1p32.1-p31.3 
                 1.23 
                 0.04030 
               
               
                 209069_s_at 
                 BC001124 
                 H3F3B 
                 H3 histone, family 3B (H3.3B) 
                 17q25 
                 1.23 
                 0.00480 
               
               
                 207014_at 
                 NM_000807 
                 GABRA2 
                 gamma-aminobutyric acid (GABA) A receptor, alpha 2 
                 4p12 
                 1.22 
                 0.01050 
               
               
                 204964_s_at 
                 NM_005086 
                 SSPN 
                 sarcospan (Kras oncogene-associated gene) 
                 12p11.2 
                 1.21 
                 0.04060 
               
               
                 212649_at 
                 AL079292 
                 DHX29 
                 DEAH (Asp-Glu-Ala-His) box polypeptide 29 
                 5q11.2 
                 1.21 
                 0.04200 
               
               
                 215450_at 
                 W87901 
                 SNRPE 
                 small nuclear ribonucleoprotein polypeptide E 
                 1q32 
                 1.21 
                 0.03350 
               
               
                 217936_at 
                 AW044631 
                 ARHGAP5 
                 rho GTPase activating protein 5 
                 14q12* 
                 1.21 
                 0.03890 
               
               
                 208920_at 
                 AV752215 
                 SRI 
                 sorcin 
                 7q21.1 
                 1.20 
                 0.02480 
               
               
                 209024_s_at 
                 AI472757 
                 SYNCRIP 
                 synaptotagmin binding, cytoplasmic RNA interacting protein 
                 6q14-q15 
                 1.20 
                 0.01850 
               
               
                 209600_s_at 
                 S69189 
                 ACOX1 
                 acyl-Coenzyme A oxidase 1, palmitoyl 
                 17q24-q25* 
                 1.20 
                 0.00480 
               
               
                 212044_s_at 
                 BE737027 
                 RPL27A 
                 hypothetical protein MGC10850 
                 11p15 
                 1.20 
                 0.02780 
               
               
                 218490_s_at 
                 NM_018443 
                 ZNF302 
                 zinc finger protein 302 
                 19q13.11 
                 1.20 
                 0.03440 
               
               
                 200943_at 
                 NM_004965 
                 HMGN1 
                 high-mobility group nucleosome binding domain 1 
                 21q22.3 
                 1.19 
                 0.00920 
               
               
                 222035_s_at 
                 AI984479 
                 PAPOLA 
                 poly(A) polymerase alpha 
                 14q32.31 
                 1.19 
                 0.02600 
               
               
                 203202_at 
                 AI950314 
                 HRB2 
                 HIV-1 rev binding protein 2 
                 12q21.1 
                 1.18 
                 0.02550 
               
               
                 203628_at 
                 H05812 
                 IGF1R 
                 insulin-like growth factor 1 receptor 
                 15q26.3 
                 1.18 
                 0.03650 
               
               
                 205475_at 
                 NM_007281 
                 SCRG1 
                 scrapie responsive protein 1 
                 4q31-q32 
                 1.18 
                 0.02860 
               
               
                 218859_s_at 
                 NM_016649 
                 C20orf6 
                 chromosome 20 open reading frame 6 
                 20p12.1* 
                 1.18 
                 0.03300 
               
               
                 201965_s_at 
                 NM_015046 
                 KIAA0625 
                 senataxin 
                 9q34.13 
                 1.17 
                 0.01070 
               
               
                 203549_s_at 
                 NM_000237 
                 LPL 
                 lipoprotein lipase 
                 8p22* 
                 1.17 
                 0.04020 
               
               
                 208990_s_at 
                 AF132362 
                 HNRPH3 
                 heterogeneous nuclear ribonucleoprotein H3 (2H9) 
                 10q22 
                 1.17 
                 0.01960 
               
               
                 210970_s_at 
                 AF235049 
                 IBTK 
                 inhibitor of Bruton agammaglobulinemia tyrosine kinase 
                 6q14.1 
                 1.17 
                 0.04700 
               
               
                 212179_at 
                 AW157501 
                 C6orf111 
                 chromosome 6 open reading frame 111 
                 6q16.3* 
                 1.17 
                 0.04900 
               
               
                 212689_s_at 
                 AA524505 
                 JMJD1A 
                 jumonji domain containing 1A 
                 2p11.2* 
                 1.17 
                 0.01230 
               
               
                 214352_s_at 
                 BF673699 
                 KRAS2 
                 v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog 
                 12p12.1 
                 1.17 
                 0.00330 
               
               
                 221960_s_at 
                 AI189609 
                 RAB2 
                 RAB2, member RAS oncogene family 
                 8q12.1 
                 1.17 
                 0.02270 
               
               
                 201129_at 
                 NM_006276 
                 SFRS7 
                 splicing factor, arginine/serine-rich 7, 35 kDa 
                 2p22.1 
                 1.16 
                 0.03180 
               
               
                 201918_at 
                 AI927944 
                 FLJ10618 
                 hypothetical protein FLJ10618 
                 3q23 
                 1.16 
                 0.04000 
               
               
                 207010_at 
                 NM_000812 
                 GABRB1 
                 gamma-aminobutyric acid (GABA) A receptor, beta 1 
                 4p12 
                 1.16 
                 0.04360 
               
               
                 209763_at 
                 AL049176 
                 CHRDL1 
                 chordin-like 1 
                 Xq23 
                 1.16 
                 0.03340 
               
               
                 212368_at 
                 AA972711 
                 ZNF292 
                 zinc finger protein 292 
                 6q15* 
                 1.16 
                 0.04620 
               
               
                 213792_s_at 
                 AA485908 
                 INSR 
                 insulin receptor 
                 19p13.3-p13.2 
                 1.16 
                 0.01300 
               
               
                 214433_s_at 
                 NM_003944 
                 SELENBP1 
                 selenium binding protein 1 
                 1q21-q22 
                 1.16 
                 0.04510 
               
               
                 218183_at 
                 NM_013399 
                 C16orf5 
                 chromosome 16 open reading frame 5 
                 16p13.3 
                 1.16 
                 0.03280 
               
               
                 218595_s_at 
                 NM_018072 
                 FLJ10359 
                 hypothetical protein FLJ10359 
                 1q43 
                 1.16 
                 0.01920 
               
               
                 202258_s_at 
                 U50532 
                 PFAAP5 
                 phosphonoformate immuno-associated protein 5 
                 13q12-q13 
                 1.15 
                 0.02060 
               
               
                 211929_at 
                 AA527502 
                 HNRPA3 
                 heterogeneous nuclear ribonucleoprotein A3 
                 2q31.2 
                 1.15 
                 0.01410 
               
               
                 219819_s_at 
                 NM_014018 
                 MRPS28 
                 mitochondrial ribosomal protein S28 
                 8q21.1-q21.2 
                 1.15 
                 0.00580 
               
               
                 200616_s_at 
                 BC000371 
                 KIAA0152 
                 KIAA0152 gene product 
                 12q24.31 
                 1.14 
                 0.02490 
               
               
                 200920_s_at 
                 AL535380 
                 BTG1 
                 B-cell translocation gene 1, anti-proliferative 
                 12q22 
                 1.14 
                 0.04020 
               
               
                 201138_s_at 
                 BG532929 
                 SSB 
                 Sjogren syndrome antigen B (autoantigen La) 
                 2q31.1 
                 1.14 
                 0.00570 
               
               
                 201637_s_at 
                 NM_005087 
                 FXR1 
                 fragile X mental retardation, autosomal homolog 1 
                 3q28 
                 1.14 
                 0.04690 
               
               
                 201831_s_at 
                 BE875592 
                 VDP 
                 vesicle docking protein p115 
                 4q21.1 
                 1.14 
                 0.02890 
               
               
                 202324_s_at 
                 NM_022735 
                 ACBD3 
                 acyl-Coenzyme A binding domain containing 3 
                 1q42.12 
                 1.14 
                 0.04460 
               
               
                 203526_s_at 
                 M74088 
                 APC 
                 adenomatosis polyposis coli 
                 5q21-q22 
                 1.14 
                 0.02510 
               
               
                 207557_s_at 
                 NM_001035 
                 RYR2 
                 ryanodine receptor 2 (cardiac) 
                 1q42.1-q43 
                 1.14 
                 0.01030 
               
               
                 208663_s_at 
                 AI652848 
                 TTC3 
                 tetratricopeptide repeat domain 3 
                 21q22.2 
                 1.14 
                 0.04010 
               
               
                 209049_s_at 
                 BC001004 
                 PRKCBP1 
                 protein kinase C binding protein 1 
                 20q13.12 
                 1.14 
                 0.03340 
               
               
                 212332_at 
                 BF110947 
                 RBL2 
                 retinoblastoma-like 2 (p130) 
                 16q12.2* 
                 1.14 
                 0.04480 
               
               
                 216039_at 
                 D38503 
                 PMS2L1 
                 postmeiotic segregation increased 2-like 1 
                 7q22.1 
                 1.14 
                 0.03510 
               
               
                 217975_at 
                 NM_016303 
                 WBP5 
                 WW domain binding protein 5 
                 Xq22.2 
                 1.14 
                 0.02620 
               
               
                 200944_s_at 
                 NM_004965 
                 HMGN1 
                 high-mobility group nucleosome binding domain 1 
                 21q22.3 
                 1.13 
                 0.02050 
               
               
                 201773_at 
                 NM_015339 
                 ADNP 
                 activity-dependent neuroprotector 
                 20q13.13 
                 1.13 
                 0.01290 
               
               
                 203133_at 
                 NM_006808 
                 SEC61B 
                 Sec61 beta subunit 
                 9q22.32-q31.3 
                 1.13 
                 0.00260 
               
               
                 208921_s_at 
                 L12387 
                 SRI 
                 sorcin 
                 7q21.1 
                 1.13 
                 0.02490 
               
               
                 210588_x_at 
                 L32610 
                 HNRPH3 
                 heterogeneous nuclear ribonucleoprotein H3 (2H9) 
                 10q22 
                 1.13 
                 0.04050 
               
               
                 211930_at 
                 AW080932 
                 HNRPA3 
                 heterogeneous nuclear ribonucleoprotein A3 
                 2q31.2 
                 1.13 
                 0.02060 
               
               
                 212519_at 
                 AL518159 
                 UBE2E1 
                 ubiquitin-conjugating enzyme E2E 1 (UBC4/5 homolog, yeast) 
                 3p24.2* 
                 1.13 
                 0.03680 
               
               
                 216399_s_at 
                 AK025663 
                 ZNF291 
                 zinc finger protein 291 
                 15q24 
                 1.13 
                 0.00080 
               
               
                 218435_at 
                 NM_013238 
                 DNAJD1 
                 DnaJ (Hsp40) homolog, subfamily D, member 1 
                 13q14.1 
                 1.13 
                 0.01580 
               
               
                 55692_at 
                 W22924 
                 ELMO2 
                 engulfment and cell motility 2 (ced-12 homolog,  C. elegans ) 
                 20q13 
                 1.13 
                 0.03650 
               
               
                 202299_s_at 
                 NM_006402 
                 HBXIP 
                 hepatitis B virus x interacting protein 
                 1p13.3* 
                 1.12 
                 0.04400 
               
               
                 207543_s_at 
                 NM_000917 
                 P4HA1 
                 procollagen-proline, 2-oxoglutarate 4-dioxygenase 
                 10q21.3-q23.1 
                 1.12 
                 0.03640 
               
               
                   
                   
                   
                 (proline 4-hydroxylase), alpha polypeptide I 
               
               
                 209180_at 
                 U49245 
                 RABGGTB 
                 rab geranylgeranyltransferase, beta subunit 
                 1p31 
                 1.12 
                 0.02210 
               
               
                 211784_s_at 
                 BC006181 
                 SFRS1 
                 splicing factor, arginine/serine-rich 1 (splicing factor 2, 
                 17q21.3-q22* 
                 1.12 
                 0.02460 
               
               
                   
                   
                   
                 alternate splicing factor) 
               
               
                 211828_s_at 
                 AF172268 
                 TNIK 
                 TRAF2 and NCK interacting kinase 
                 3q26.2 
                 1.12 
                 0.04840 
               
               
                 221613_s_at 
                 AL136598 
                 ZA20D3 
                 zinc finger, A20 domain containing 3 
                 15q25.1 
                 1.12 
                 0.04060 
               
               
                 200020_at 
                 NM_007375 
                 TARDBP 
                 TAR DNA binding protein 
                 1p36.22 
                 1.11 
                 0.04070 
               
               
                 200063_s_at 
                 BC002398 
                 NPM1 
                 nucleophosmin (nucleolar phosphoprotein B23, numatrin) 
                 5q35 
                 1.11 
                 0.03260 
               
               
                 202266_at 
                 NM_016614 
                 TTRAP 
                 TRAF and TNF receptor associated protein 
                 6p22.3-p22.1* 
                 1.11 
                 0.04520 
               
               
                 202301_s_at 
                 BE396879 
                 FLJ11021 
                 similar to splicing factor, arginine/serine-rich 4 
                 12q24.31 
                 1.11 
                 0.02420 
               
               
                 209059_s_at 
                 AB002282 
                 EDF1 
                 endothelial differentiation-related factor 1 
                 9q34.3 
                 1.11 
                 0.02090 
               
               
                 214053_at 
                 AW772192 
                 ERBB4 
                 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) 
                 2q33.3-q34 
                 1.11 
                 0.04040 
               
               
                 217869_at 
                 NM_016142 
                 HSD17B12 
                 hydroxysteroid (17-beta) dehydrogenase 12 
                 11p11.2 
                 1.11 
                 0.03900 
               
               
                 222216_s_at 
                 AK026857 
                 MRPL17 
                 mitochondrial ribosomal protein L17 
                 11p15.5-p15.4 
                 1.11 
                 0.01650 
               
               
                 200977_s_at 
                 AF090891 
                 TAX1BP1 
                 tax1 (human T-cell leukemia virus type I) binding protein 1 
                 7p15 
                 1.10 
                 0.03050 
               
               
                 201812_s_at 
                 NM_019059 
                 TOMM7 
                 translocase of outer mitochondrial membrane 7 homolog (yeast) 
                 7p15.3 
                 1.10 
                 0.04140 
               
               
                 203870_at 
                 BE856374 
                 USP46 
                 ubiquitin specific protease 46 
                 4q12 
                 1.10 
                 0.04410 
               
               
                 203880_at 
                 NM_005694 
                 COX17 
                 COX17 homolog, cytochrome c oxidase assembly protein (yeast) 
                 3q13.33 
                 1.10 
                 0.01780 
               
               
                 208726_s_at 
                 BC000461 
                 EIF2S2 
                 eukaryotic translation initiation factor 2, subunit 2 beta, 38 kDa 
                 20pter-q12* 
                 1.10 
                 0.03110 
               
               
                 208895_s_at 
                 BG530850 
                 DDX18 
                 DEAD (Asp-Glu-Ala-Asp) box polypeptide 18 
                 2q14.1* 
                 1.10 
                 0.04930 
               
               
                 217724_at 
                 AF131807 
                 PAI-RBP1 
                 PAI-1 mRNA-binding protein 
                 1p31-p22 
                 1.10 
                 0.01610 
               
               
                 201157_s_at 
                 AF020500 
                 NMT1 
                 N-myristoyltransferase 1 
                 17q21.31 
                 1.09 
                 0.00980 
               
               
                 201606_s_at 
                 BE796924 
                 PWP1 
                 nuclear phosphoprotein similar to  S. cerevisiae  PWP1 
                 12q23.3 
                 1.09 
                 0.04390 
               
               
                 203621_at 
                 NM_002492 
                 NDUFB5 
                 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16 kDa 
                 3q26.33 
                 1.09 
                 0.02910 
               
               
                 209224_s_at 
                 BC003674 
                 NDUFA2 
                 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8 kDa 
                 5q31* 
                 1.09 
                 0.02260 
               
               
                 217898_at 
                 NM_020154 
                 C15orf24 
                 chromosome 15 open reading frame 24 
                 15q14 
                 1.09 
                 0.01910 
               
               
                 217907_at 
                 NM_014161 
                 MRPL18 
                 mitochondrial ribosomal protein L18 
                 6q25.3 
                 1.09 
                 0.00370 
               
               
                 218123_at 
                 NM_017835 
                 C21orf59 
                 chromosome 21 open reading frame 59 
                 21q22.1 
                 1.09 
                 0.00130 
               
               
                 200728_at 
                 BE566290 
                 ACTR2 
                 actin-related protein 2 homolog (yeast) 
                 2p14 
                 1.08 
                 0.04030 
               
               
                 217774_s_at 
                 NM_016404 
                 HSPC152 
                 hypothetical protein HSPC152 
                 11q13.1 
                 1.08 
                 0.02850 
               
               
                 217940_s_at 
                 NM_018210 
                 FLJ10769 
                 hypothetical protein FLJ10769 
                 13q34 
                 1.08 
                 0.01660 
               
               
                 218142_s_at 
                 NM_016302 
                 CRBN 
                 cereblon 
                 3p26.2 
                 1.08 
                 0.01660 
               
               
                 201134_x_at 
                 NM_001867 
                 COX7C 
                 cytochrome c oxidase subunit Vllc 
                 5q14 
                 1.07 
                 0.04030 
               
               
                 203478_at 
                 NM_002494 
                 NDUFC1 
                 NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 
                 4q28.2-q31.1 
                 1.07 
                 0.00900 
               
               
                   
                   
                   
                 1, 6 kDa 
               
               
                 217491_x_at 
                 AF042165 
                 COX7CP1 
                 cytochrome c oxidase subunit Vllc pseudogene 1 
                 13q14-q21 
                 1.07 
                 0.03650 
               
               
                 217874_at 
                 NM_003849 
                 SUCLG1 
                 succinate-CoA ligase, GDP-forming, alpha subunit 
                 2p11.2* 
                 1.06 
                 0.02870 
               
               
                 200021_at 
                 NM_005507 
                 CFL1 
                 cofilin 1 (non-muscle) 
                 11q13 
                 −1.06 
                 0.04670 
               
               
                 203929_s_at 
                 AI056359 
                 MAPT 
                 microtubule-associated protein tau 
                 17q21.1 
                 −1.07 
                 0.04770 
               
               
                 211780_x_at 
                 BC006163 
                 DCTN1 
                 dynactin 1 (p150, glued homolog,  Drosophila ) 
                 2p13 
                 −1.07 
                 0.03780 
               
               
                 213867_x_at 
                 AA809056 
                 ARHGEF10 
                 rho guanine nucleotide exchange factor (GEF) 10 
                 8p23 
                 −1.07 
                 0.02110 
               
               
                 201864_at 
                 NM_001493 
                 GDI1 
                 GDP dissociation inhibitor 1 
                 Xq28 
                 −1.08 
                 0.02220 
               
               
                 202508_s_at 
                 NM_003081 
                 SNAP25 
                 synaptosomal-associated protein, 25 kDa 
                 20p12-p11.2* 
                 −1.08 
                 0.02980 
               
               
                 202752_x_at 
                 NM_012244 
                 SLC7A8 
                 solute carrier family 7 (cationic amino acid transporter, y+ system), 
                 14q11.2* 
                 −1.08 
                 0.01790 
               
               
                   
                   
                   
                 member 8 
               
               
                 203103_s_at 
                 NM_014502 
                 PRP19 
                 PRP19/PSO4 homolog ( S. cerevisiae ) 
                 11q12.2 
                 −1.08 
                 0.01750 
               
               
                 206213_at 
                 NM_003394 
                 WNT10B 
                 wingless-type MMTV integration site family, member 10B 
                 12q13 
                 −1.08 
                 0.04540 
               
               
                 214626_s_at 
                 AK026548 
                 GANAB 
                 glucosidase, alpha; neutral AB 
                 11q12.3 
                 −1.08 
                 0.01490 
               
               
                 221966_at 
                 AA813194 
                 RH98400 
                 chromosome 11 hypothetical protein ORF4 
                 11cen-q22.3* 
                 −1.08 
                 0.01840 
               
               
                 35265_at 
                 U31501 
                 FXR2 
                 fragile X mental retardation, autosomal homolog 2 
                 17p13.1 
                 −1.08 
                 0.00660 
               
               
                 200758_s_at 
                 AI361227 
                 NFE2L1 
                 nuclear factor (erythroid-derived 2)-like 1 
                 17q21.3 
                 −1.09 
                 0.01890 
               
               
                 202210_x_at 
                 NM_019884 
                 GSK3A 
                 glycogen synthase kinase 3 alpha 
                 19q13.2 
                 −1.09 
                 0.02490 
               
               
                 202801_at 
                 NM_002730 
                 PRKACA 
                 protein kinase, cAMP-dependent, catalytic, alpha 
                 19p13.1 
                 −1.09 
                 0.04400 
               
               
                 203906_at 
                 AI652645 
                 IQSEC1 
                 IQ motif and Sec7 domain 1 
                 3p25.2* 
                 −1.09 
                 0.04350 
               
               
                 205331_s_at 
                 NM_016606 
                 C5orf19 
                 chromosome 5 open reading frame 19 
                 5q31* 
                 −1.09 
                 0.01970 
               
               
                 207366_at 
                 NM_002251 
                 KCNS1 
                 potassium voltage-gated channel, delayed-rectifier, 
                 20q12 
                 −1.09 
                 0.04360 
               
               
                   
                   
                   
                 subfamily S, member 1 
               
               
                 208390_s_at 
                 U01104 
                 GLP1R 
                 glucagon-like peptide 1 receptor 
                 6p21* 
                 −1.09 
                 0.03080 
               
               
                 208829_at 
                 AF029750 
                 TAPBP 
                 TAP binding protein (tapasin) 
                 6p21.3* 
                 −1.09 
                 0.02930 
               
               
                 214354_x_at 
                 T91506 
                 SFTPB 
                 surfactant, pulmonary-associated protein B 
                 2p12-p11.2* 
                 −1.09 
                 0.02470 
               
               
                 219521_at 
                 NM_018644 
                 B3GAT1 
                 beta-1,3-glucuronyltransferase 1 (glucuronosyltransferase P) 
                 11q25 
                 −1.09 
                 0.04350 
               
               
                 220465_at 
                 NM_024988 
                 FLJ12355 
                 hypothetical protein FLJ12355 
                 19q13.11 
                 −1.09 
                 0.00970 
               
               
                 221560_at 
                 AB049127 
                 MARK4 
                 MAP/microtubule affinity-regulating kinase 4 
                 19q13.3 
                 −1.09 
                 0.02540 
               
               
                 200001_at 
                 NM_001749 
                 CAPNS1 
                 calpain, small subunit 1 
                 19q13.12 
                 −1.10 
                 0.01740 
               
               
                 200639_s_at 
                 NM_003406 
                 YWHAZ 
                 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase 
                 8q23.1 
                 −1.10 
                 0.03720 
               
               
                   
                   
                   
                 activation protein, zeta polypeptide 
               
               
                 200752_s_at 
                 NM_005186 
                 CAPN1 
                 calpain 1, (mu/l) large subunit 
                 11q13 
                 −1.10 
                 0.02210 
               
               
                 202676_x_at 
                 NM_006712 
                 FASTK 
                 FAST kinase 
                 7q35 
                 −1.10 
                 0.04340 
               
               
                 202806_at 
                 NM_004395 
                 DBN1 
                 drebrin 1 
                 5q35.3 
                 −1.10 
                 0.02130 
               
               
                 203618_at 
                 AB023167 
                 FAIM2 
                 Fas apoptotic inhibitory molecule 2 
                 12q13 
                 −1.10 
                 0.02870 
               
               
                 204947_at 
                 NM_005225 
                 E2F1 
                 E2F transcription factor 1 
                 20q11.2 
                 −1.10 
                 0.00300 
               
               
                 204980_at 
                 NM_004898 
                 CLOCK 
                 clock homolog (mouse) 
                 4q12 
                 −1.10 
                 0.04370 
               
               
                 209229_s_at 
                 BC002799 
                 KIAA1115 
                 KIAA1115 
                 19q13.42 
                 −1.10 
                 0.01650 
               
               
                 210975_x_at 
                 BC000377 
                 FASTK 
                 FAST kinase 
                 7q35 
                 −1.10 
                 0.03390 
               
               
                 211677_x_at 
                 AF062733 
                 IGSF4B 
                 immunoglobulin superfamily, member 4B 
                 1q21.2-q22 
                 −1.10 
                 0.02190 
               
               
                 214903_at 
                 AF070580 
                 FLJ42519 
                 CDNA FLJ42519 fis, clone BRACE3000787 
                 1q32 
                 −1.10 
                 0.03390 
               
               
                 217419_x_at 
                 AK021586 
                 AGRN 
                 agrin 
                 1p36.33 
                 −1.10 
                 0.03320 
               
               
                 219400_at 
                 NM_003632 
                 CNTNAP1 
                 contactin associated protein 1 
                 17q21 
                 −1.10 
                 0.03850 
               
               
                 221901_at 
                 BF516072 
                 KIAA1644 
                 KIAA1644 protein 
                 22q13 
                 −1.10 
                 0.03390 
               
               
                 47560_at 
                 AI525402 
                 LPHN1 
                 latrophilin 1 
                 19p13.2 
                 −1.10 
                 0.02260 
               
               
                 203151_at 
                 AW296788 
                 MAP1A 
                 microtubule-associated protein 1A 
                 15q13-qter 
                 −1.11 
                 0.02680 
               
               
                 203831_at 
                 NM_014925 
                 KIAA1002 
                 KIAA1002 protein 
                 12q13.3 
                 −1.11 
                 0.00700 
               
               
                 205325_at 
                 NM_014759 
                 PHYHIP 
                 phytanoyl-CoA hydroxylase interacting protein 
                 8p21.3* 
                 −1.11 
                 0.04680 
               
               
                 208823_s_at 
                 BE787860 
                 PCTK1 
                 PCTAIRE protein kinase 1 
                 Xp11.3-p11.23 
                 −1.11 
                 0.03640 
               
               
                 211240_x_at 
                 AB002382 
                 CTNND1 
                 catenin (cadherin-associated protein), delta 1 
                 11q11 
                 −1.11 
                 0.01540 
               
               
                 217766_s_at 
                 NM_014313 
                 SMP1 
                 small membrane protein 1 
                 1p36.11 
                 −1.11 
                 0.01340 
               
               
                 220974_x_at 
                 NM_030971 
                 BA108L7.2 
                 similar to rat tricarboxylate carrier-like protein 
                 10q24.32 
                 −1.11 
                 0.00260 
               
               
                 221535_at 
                 AL136897 
                 FLJ11301 
                 hypothetical protein FLJ11301 
                 3q29 
                 −1.11 
                 0.00450 
               
               
                 203244_at 
                 NM_000319 
                 PEX5 
                 peroxisomal biogenesis factor 5 
                 12p13.3 
                 −1.12 
                 0.00890 
               
               
                 203264_s_at 
                 NM_015185 
                 ARHGEF9 
                 Cdc42 guanine nucleotide exchange factor (GEF) 9 
                 Xq11.2 
                 −1.12 
                 0.03980 
               
               
                 207629_s_at 
                 NM_004723 
                 ARHGEF2 
                 rho/rac guanine nucleotide exchange factor (GEF) 2 
                 1q21-q22 
                 −1.12 
                 0.04820 
               
               
                 209435_s_at 
                 BC000265 
                 ARHGEF2 
                 rho/rac guanine nucleotide exchange factor (GEF) 
                 1q21-q22 
                 −1.12 
                 0.00820 
               
               
                 217637_at 
                 R25692 
                 Unknown 
                 full length insert cDNA clone ZE05A03 
                 20q13.1 
                 −1.12 
                 0.04500 
               
               
                 212252_at 
                 AA181179 
                 CAMKK2 
                 calcium/calmodulin-dependent protein kinase kinase 2, beta 
                 12q24.2 
                 −1.13 
                 0.03980 
               
               
                 212699_at 
                 BE222801 
                 SCAMP5 
                 secretory carrier membrane protein 5 
                 15q23 
                 −1.13 
                 0.04090 
               
               
                 204893_s_at 
                 NM_004799 
                 ZFYVE9 
                 zinc finger, FYVE domain containing 9 
                 1p32.3 
                 −1.14 
                 0.04400 
               
               
                 211934_x_at 
                 W87689 
                 GANAB 
                 glucosidase, alpha; neutral AB 
                 11q12.3 
                 −1.14 
                 0.01130 
               
               
                 212285_s_at 
                 AW008051 
                 AGRN 
                 agrin 
                 1p36.33 
                 −1.14 
                 0.00740 
               
               
                 217991_x_at 
                 NM_018070 
                 SSBP3 
                 single stranded DNA binding protein 3 
                 1p32.3 
                 −1.14 
                 0.01450 
               
               
                 218952_at 
                 NM_013271 
                 PCSK1N 
                 proprotein convertase subtilisin/kexin type 1 inhibitor 
                 Xp11.23 
                 −1.14 
                 0.03060 
               
               
                 205508_at 
                 NM_001037 
                 SCN1B 
                 sodium channel, voltage-gated, type I, beta 
                 19q13.1 
                 −1.15 
                 0.00770 
               
               
                 209728_at 
                 BC005312 
                 HLA-DRB1 
                 major histocompatibility complex, class II, DR beta 1 
                 6p21.3* 
                 −1.17 
                 0.04220 
               
               
                 219724_s_at 
                 NM_014796 
                 KIAA0748 
                 KIAA0748 gene product 
                 12q13.2 
                 −1.21 
                 0.00310 
               
               
                 203337_x_at 
                 NM_004763 
                 ITGB1BP1 
                 integrin beta 1 binding protein 1 
                 2p25.2 
                 −1.29 
                 0.01930 
               
               
                 217427_s_at 
                 X75296 
                 HIRA 
                 HIR histone cell cycle regulation defective homolog A ( S. cerevisiae ) 
                 22q11.2* 
                 −1.32 
                 0.00940 
               
               
                 205048_s_at 
                 NM_003832 
                 PSPHL 
                 phosphoserine phosphatase-like 
                 7q11.2 
                 −2.14 
                 0.04420 
               
               
                   
               
               
                 *Implicated in SZ by meta-analysis of genome-wide linkage studies (22) 
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Genes differentially expressed in PBCs in SZ 
               
             
          
           
               
                 Affymetrix 
                   
                   
                   
                   
                 Fold- 
                   
               
               
                 Probe 
                 Accession 
                 Gene 
                 Gene 
                 Chromosomal 
                 Change 
               
               
                 Number 
                 Number 
                 Symbol 
                 Product 
                 Locus 
                 in SZ 
                 p 
               
               
                   
               
             
          
           
               
                 210746_s_at 
                 M30646 
                 EPB42 
                 erythrocyte membrane protein band 4.2 
                 15q15-q21 
                 2.35 
                 0.00053 
               
               
                 211560_s_at 
                 AF130113 
                 ALAS2 
                 aminolevulinate, delta-, synthase 2 
                 Xp11.21 
                 2.34 
                 0.00111 
               
               
                   
                   
                   
                 (sideroblastic/hypochromic anemia) 
               
               
                 213524_s_at 
                 NM_015714 
                 G0S2 
                 putative lymphocyte G0/G1 switch gene 
                 1q32.2-q41 
                 2.28 
                 0.00146 
               
               
                 219672_at 
                 NM_016633 
                 ERAF 
                 erythroid associated factor 
                 16p11.2 
                 2.13 
                 0.00029 
               
               
                 209890_at 
                 AF065389 
                 TM4SF9 
                 transmembrane 4 superfamily member 9 
                 4q23 
                 2.12 
                 0.00203 
               
               
                 203691_at 
                 NM_002638 
                 PI3 
                 protease inhibitor 3, skin-derived (SKALP) 
                 20q12-q13 
                 2.05 
                 0.00001 
               
               
                 211781_x_at 
                 BC006164 
                 Unknown 
                 hypothetical protein MGC13219 
                 Unknown 
                 2.04 
                 0.00007 
               
               
                 219630_at 
                 NM_005764 
                 MAP17 
                 membrane-associated protein 17 
                 1p33 
                 2.01 
                 0.00011 
               
               
                 205950_s_at 
                 NM_001738 
                 CA1 
                 carbonic anhydrase I 
                 8q13-q22.1 
                 1.99 
                 0.00049 
               
               
                 210395_x_at 
                 AF116676 
                 MYL4 
                 myosin, light polypeptide 4, alkali; atrial, embryonic 
                 17q21-qter 
                 1.99 
                 0.00003 
               
               
                 204466_s_at 
                 BG260394 
                 SNCA 
                 synuclein, alpha (non A4 component of amyloid precursor) 
                 4q21 
                 1.95 
                 0.00119 
               
               
                 214433_s_at 
                 NM_003944 
                 SELENBP1 
                 selenium binding protein 1 
                 1q21-q22 
                 1.95 
                 0.00093 
               
               
                 201178_at 
                 NM_012179 
                 FBXO7 
                 F-box protein 7 
                 22q12-q13 
                 1.91 
                 0.00025 
               
               
                 211475_s_at 
                 AF116273 
                 BAG1 
                 BCL2-associated athanogene 
                 9p12 
                 1.89 
                 0.00175 
               
               
                 206834_at 
                 NM_000519 
                 HBD 
                 hemoglobin, delta 
                 11p15.5 
                 1.86 
                 0.00132 
               
               
                 210088_x_at 
                 M36172 
                 MYL4 
                 myosin, light polypeptide 4, alkali; atrial, embryonic 
                 17q21-qter 
                 1.84 
                 0.00004 
               
               
                 202219_at 
                 NM_005629 
                 SLC6A8 
                 solute carrier family 6 (neurotransmitter transporter, creatine), 
                 Xq28 
                 1.83 
                 0.00026 
               
               
                   
                   
                   
                 member 8 
               
               
                 218872_at 
                 NM_017899 
                 TSC 
                 hypothetical protein FLJ20607 
                 12q24.22 
                 1.83 
                 0.00019 
               
               
                 201161_s_at 
                 NM_003651 
                 CSDA 
                 cold shock domain protein A 
                 12p13.1 
                 1.81 
                 0.00240 
               
               
                 202387_at 
                 NM_004323 
                 BAG1 
                 BCL2-associated athanogene 
                 9p12 
                 1.80 
                 0.00130 
               
               
                 204419_x_at 
                 NM_000184 
                 HBG2 
                 hemoglobin, gamma G 
                 11p15.5 
                 1.80 
                 0.00501 
               
               
                 204467_s_at 
                 NM_000345 
                 SNCA 
                 synuclein, alpha (non A4 component of amyloid precursor) 
                 4q21 
                 1.80 
                 0.00256 
               
               
                 216054_x_at 
                 X58851 
                 MYL4 
                 myosin, light polypeptide 4, alkali; atrial, embryonic 
                 17q21-qter 
                 1.79 
                 0.00002 
               
               
                 204187_at 
                 NM_006877 
                 GMPR 
                 guanosine monophosphate reductase 
                 6p23 
                 1.77 
                 0.00011 
               
               
                 220757_s_at 
                 NM_025241 
                 UBXD1 
                 UBX domain containing 1 
                 19p13 
                 1.77 
                 0.00434 
               
               
                 202947_s_at 
                 NM_002101 
                 GYPC 
                 glycophorin C (Gerbich blood group) 
                 2q14-q21 
                 1.73 
                 0.00752 
               
               
                 202201_at 
                 NM_000713 
                 BLVRB 
                 biliverdin reductase B (flavin reductase (NADPH)) 
                 19q13.1-q13.2 
                 1.70 
                 0.00390 
               
               
                 204848_x_at 
                 NM_000559 
                 HBG1 
                 hemoglobin, gamma A 
                 11p15.5 
                 1.69 
                 0.00779 
               
               
                 202859_x_at 
                 NM_000584 
                 IL8 
                 interleukin 8 
                 4q13-q21 
                 1.68 
                 0.00347 
               
               
                 207827_x_at 
                 L36675 
                 SNCA 
                 synuclein, alpha (non A4 component of amyloid precursor) 
                 4q21 
                 1.68 
                 0.00061 
               
               
                 211546_x_at 
                 L36674 
                 SNCA 
                 synuclein, alpha (non A4 component of amyloid precursor) 
                 4q21 
                 1.68 
                 0.00008 
               
               
                 200844_s_at 
                 BE869583 
                 PRDX6 
                 peroxiredoxin 6 
                 1q25.1 
                 1.66 
                 0.00251 
               
               
                 202364_at 
                 NM_005962 
                 MXI1 
                 MAX interactor 1 
                 10q24-q25 
                 1.66 
                 0.00005 
               
               
                 204505_s_at 
                 NM_001978 
                 EPB49 
                 erythrocyte membrane protein band 4.9 (dematin) 
                 8p21.1 
                 1.65 
                 0.00214 
               
               
                 214273_x_at 
                 AV704353 
                 C16orf35 
                 chromosome 16 open reading frame 35 
                 16p13.3 
                 1.65 
                 0.00131 
               
               
                 217748_at 
                 NM_015999 
                 ADIPOR1 
                 adiponectin receptor 1 
                 1p36.13-q41 
                 1.65 
                 0.00138 
               
               
                 220807_at 
                 NM_005331 
                 HBQ1 
                 hemoglobin, theta 1 
                 16p13.3 
                 1.62 
                 0.00439 
               
               
                 206207_at 
                 NM_001828 
                 CLC 
                 Charcot-Leyden crystal protein 
                 19q13.1 
                 1.61 
                 0.00009 
               
               
                 210638_s_at 
                 AF176704 
                 FBXO9 
                 F-box protein 9 
                 6p12.3-p11.2 
                 1.61 
                 0.00001 
               
               
                 202074_s_at 
                 NM_021980 
                 OPTN 
                 optineurin 
                 10p13 
                 1.60 
                 0.00048 
               
               
                 202210_x_at 
                 NM_019884 
                 GSK3A 
                 glycogen synthase kinase 3 alpha 
                 19q13.2 
                 1.59 
                 0.00044 
               
               
                 205592_at 
                 X77737 
                 SLC4A1 
                 solute carrier family 4, anion exchanger, member 1 
                 17q21-q22 
                 1.59 
                 0.00400 
               
               
                   
                   
                   
                 (erythrocyte membrane protein band 3, Diego blood group) 
               
               
                 221479_s_at 
                 AF060922 
                 BNIP3L 
                 BCL2/adenovirus E1B 19 kDa interacting protein 3-like 
                 8p21 
                 1.56 
                 0.00543 
               
               
                 201052_s_at 
                 BG029917 
                 PSMF1 
                 proteasome (prosome, macropain) inhibitor subunit 1 (PI31) 
                 20p13 
                 1.55 
                 0.00652 
               
               
                 40850_at 
                 L37033 
                 FKBP8 
                 FK506 binding protein 8, 38 kDa 
                 19p12 
                 1.52 
                 0.00462 
               
               
                 217882_at 
                 NM_018447 
                 LOC55831 
                 30 kDa protein 
                 3p25.3 
                 1.51 
                 0.00863 
               
               
                 205863_at 
                 NM_005621 
                 S100A12 
                 S100 calcium binding protein A12 (calgranulin C) 
                 1q21 
                 1.50 
                 0.00018 
               
               
                 208949_a_at 
                 BC001120 
                 LGALS3 
                 lectin, galactoside-binding, soluble, 3 (galectin 3) 
                 14q21-q22 
                 1.47 
                 0.00157 
               
               
                 215499_at 
                 AA780381 
                 MAP2K3 
                 mitogen-activated protein kinase kinase 3 
                 17q11.2 
                 1.47 
                 0.00001 
               
               
                 203966_s_at 
                 NM_021003 
                 PPM1A 
                 protein phosphatase 1A (formerly 2C), magnesium-dependent, 
                 14q23.1 
                 1.46 
                 0.00013 
               
               
                   
                   
                   
                 alpha isoform 
               
               
                 210183_x_at 
                 AF112222 
                 PNN 
                 pinin, desmosome associated protein 
                 14q21.1 
                 1.45 
                 0.00028 
               
               
                 204018_x_at 
                 NM_000558 
                 HBA1 
                 hemoglobin, alpha 1 
                 16p13.3 
                 1.43 
                 0.00001 
               
               
                 211699_x_at 
                 AF349571 
                 HBA1 
                 hemoglobin, alpha 1 
                 16p13.3 
                 1.43 
                 0.00003 
               
               
                 217756_x_at 
                 NM_005770 
                 SERF2 
                 small EDRK-rich factor 2 
                 15q15.3 
                 1.43 
                 0.00132 
               
               
                 200633_at 
                 NM_018955 
                 UBB 
                 ubiquitin B 
                 17p12-p11.2 
                 1.41 
                 0.00031 
               
               
                 217414_x_at 
                 V00489 
                 HBA2 
                 hemoglobin, alpha 2 
                 16p13.3 
                 1.40 
                 0.00008 
               
               
                 201285_at 
                 NM_013446 
                 MKRN1 
                 makorin, ring finger protein, 1 
                 7q34 
                 1.39 
                 0.00044 
               
               
                 209116_x_at 
                 M25079 
                 HBB 
                 hemoglobin, beta 
                 11p15.5 
                 1.38 
                 0.00002 
               
               
                 211745_x_at 
                 BC005931 
                 HBA2 
                 hemoglobin, alpha 2 
                 16p13.3 
                 1.38 
                 0.00005 
               
               
                 217232_x_at 
                 AF059180 
                 HBB 
                 hemoglobin, beta 
                 11p15.5 
                 1.36 
                 0.00005 
               
               
                 214271_x_at 
                 AA281332 
                 RPL12 
                 ribosomal protein L12 
                 9q34 
                 1.35 
                 0.00001 
               
               
                 209458_x_at 
                 AF105974 
                 HBA1 
                 hemoglobin, alpha 1 
                 16p13.3 
                 1.34 
                 0.00012 
               
               
                 221700_s_at 
                 AF348700 
                 UBA52 
                 ubiquitin A-52 residue ribosomal protein fusion product 1 
                 19p13.1-p12 
                 1.33 
                 0.00005 
               
               
                 214290_s_at 
                 AI313324 
                 H2AFO 
                 H2A histone family, member O 
                 1p36.13-q24.1 
                 1.30 
                 0.00089 
               
               
                 211696_x_at 
                 AF349114 
                 HBB 
                 hemoglobin, beta 
                 11p15.5 
                 1.29 
                 0.00002 
               
               
                 217977_at 
                 NM_016332 
                 SEPX1 
                 selenoprotein X, 1 
                 16p13.3 
                 1.29 
                 0.00265 
               
               
                 214414_x_at 
                 T50399 
                 HBA1 
                 hemoglobin, alpha 1 
                 16p13.3 
                 1.26 
                 0.00076 
               
               
                 211911_x_at 
                 L07950 
                 HLA-B 
                 major histocompatibility complex, class I, B 
                 6p21.3 
                 −1.21 
                 0.00038 
               
               
                 209619_at 
                 K01144 
                 CD74 
                 CD74 antigen (invariant polypeptide of major histocompatibility 
                 5q32 
                 −1.24 
                 0.00010 
               
               
                   
                   
                   
                 complex, class II antigen-associated) 
               
               
                 200871_s_at 
                 NM_002778 
                 PSAP 
                 prosaposin (variant Gaucher disease and variant metachromatic 
                 10q21-q22 
                 −1.27 
                 0.00003 
               
               
                   
                   
                   
                 leukodystrophy) 
               
               
                 209312_x_at 
                 U65585 
                 HLA-DRB1 
                 major histocompatibility complex, class II, DR beta 1 
                 6p21.3* 
                 −1.27 
                 0.00007 
               
               
                 200904_at 
                 X56841 
                 HLA-E 
                 major histocompatibility complex, class I, E 
                 6p21.3 
                 −1.28 
                 0.00003 
               
               
                 208980_s_at 
                 M26880 
                 UBC 
                 ubiquitin C 
                 12q24.3 
                 −1.28 
                 0.00037 
               
               
                 212363_x_at 
                 AU145192 
                 ACTG1 
                 actin, gamma 1 
                 17q25 
                 −1.30 
                 0.00045 
               
               
                 205237_at 
                 NM_002003 
                 FCN1 
                 ficolin (collagen/fibrinogen domain containing) 1 
                 9q34 
                 −1.33 
                 0.00055 
               
               
                 215193_x_at 
                 AJ297586 
                 HLA-DRB1 
                 major histocompatibility complex, class II, DR beta 1 
                 6p21.3 
                 −1.33 
                 0.00006 
               
               
                 201368_at 
                 U07802 
                 ZFP36L2 
                 zinc finger protein 36, C3H type-like 2 
                 2p22.3-p21 
                 −1.35 
                 0.00018 
               
               
                 200634_at 
                 NM_005022 
                 PFN1 
                 profilin 1 
                 17p13.3 
                 −1.36 
                 0.00001 
               
               
                 200866_s_at 
                 M32221 
                 PSAP 
                 prosaposin (variant Gaucher disease and variant metachromatic 
                 10q21-q22 
                 −1.36 
                 0.00015 
               
               
                   
                   
                   
                 leukodystrophy) 
               
               
                 200920_s_at 
                 AL535380 
                 BTG1 
                 B-cell translocation gene 1, anti-proliferative 
                 12q22 
                 −1.36 
                 0.00008 
               
               
                 200772_x_at 
                 BF686442 
                 PTMA 
                 prothymosin, alpha (gene sequence 28) 
                 2q35-q36 
                 −1.37 
                 0.00032 
               
               
                 208438_s_at 
                 NM_005248 
                 FGR 
                 Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog 
                 1p36.2-p36.1 
                 −1.38 
                 0.00001 
               
               
                 219505_at 
                 NM_017424 
                 CECR1 
                 cat eye syndrome chromosome region, candidate 1 
                 22q11.2 
                 −1.38 
                 0.00001 
               
               
                 200742_s_at 
                 BG231932 
                 CLN2 
                 ceroid-lipofuscinosis, neuronal 2, late infantile 
                 11p15 
                 −1.41 
                 0.00001 
               
               
                   
                   
                   
                 (Jansky-Bielschowsky disease) 
               
               
                 200743_s_at 
                 NM_000391 
                 CLN2 
                 ceroid-lipofuscinosis, neuronal 2, late infantile 
                 11p15 
                 −1.41 
                 0.00001 
               
               
                   
                   
                   
                 (Jansky-Bielschowsky disease) 
               
               
                 205898_at 
                 U20350 
                 CX3CR1 
                 chemokine (C-X3-C motif) receptor 1 
                 3p21 
                 −1.41 
                 0.00002 
               
               
                   
                   
                   
                 isoform, 1, cardiac muscle 
               
               
                 213738_s_at 
                 AI587323 
                 ATP5A1 
                 ATP synthase, H+ transporting, mitochondrial F1 complex, 
                 18q12-q21 
                 −1.44 
                 0.00008 
               
               
                   
                   
                   
                 alpha subunit, 
               
               
                 211991_s_at 
                 M27487 
                 HLA-DPA1 
                 major histocompatibility complex, class II, DP alpha 1 
                 6p21.3 
                 −1.48 
                 0.00002 
               
               
                 212192_at 
                 AI718937 
                 KCTD12 
                 potassium channel tetramerisation domain containing 12 
                 13q22.3 
                 −1.49 
                 0.00005 
               
               
                 207419_s_at 
                 NM_002872 
                 RAC2 
                 ras-related C3 botulinum toxin substrate 2 (rho family, small GTP 
                 22q13.1 
                 −1.51 
                 0.00092 
               
               
                   
                   
                   
                 binding protein Rac2) 
               
               
                 211921_x_at 
                 AF348514 
                 PTMA 
                 prothymosin, alpha (gene sequence 28) 
                 2q35-q36 
                 −1.52 
                 0.00002 
               
               
                 204912_at 
                 NM_001558 
                 IL10RA 
                 interleukin 10 receptor, alpha 
                 11q23 
                 −1.54 
                 0.00006 
               
               
                 208743_s_at 
                 BC001359 
                 YWHAB 
                 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase 
                 20q13.1 
                 −1.54 
                 0.00003 
               
               
                   
                   
                   
                 activation protein, beta polypeptide 
               
               
                 205292_s_at 
                 NM_002137 
                 HNRPA2B1 
                 heterogeneous nuclear ribonucleoprotein A2/B1 
                 7p15 
                 −1.59 
                 0.00001 
               
               
                 203037_s_at 
                 NM_014751 
                 MTSS1 
                 metastasis suppressor 1 
                 8p22 
                 −1.60 
                 0.00002 
               
               
                 203104_at 
                 NM_005211 
                 CSF1R 
                 colony stimulating factor 1 receptor, formerly McDonough feline 
                 5q33-q35 
                 −1.63 
                 0.00001 
               
               
                   
                   
                   
                 sarcoma viral (v-fms) oncogene homolog 
               
               
                 56256_at 
                 AA150165 
                 SIDT2 
                 SID1 transmembrane family, member 2 
                 11q23.3 
                 −1.63 
                 0.00001 
               
               
                 201393_s_at 
                 NM_000876 
                 IGF2R 
                 insulin-like growth factor 2 receptor 
                 6q26 
                 −1.66 
                 0.00015 
               
               
                 211784_s_at 
                 BC006181 
                 SFRS1 
                 splicing factor, arginine/serine-rich 1 (splicing factor 2, 
                 17q21.3-q22 
                 −1.71 
                 0.00005 
               
               
                   
                   
                   
                 altemate splicing factor) 
               
               
                 214617_at 
                 AI445650 
                 PRF1 
                 perforin 1 (pore forming protein) 
                 10q22 
                 −1.71 
                 0.00001 
               
               
                 203741_s_at 
                 NM_001114 
                 ADCY7 
                 adenylate cyclase 7 
                 16q12-q13 
                 −1.73 
                 0.00002 
               
               
                 213475_s_at 
                 AC002310 
                 ITGAL 
                 integrin, alpha L (antigen CD11A (p180), lymphocyte function- 
                 16p11.2 
                 −1.73 
                 0.00001 
               
               
                   
                   
                   
                 associated antigen 1; alpha polypeptide) 
               
               
                 208988_at 
                 BE675843 
                 FBOXL11 
                 F-box and leucine-rich repeat protein 11 
                 11q13.2 
                 −1.75 
                 0.00001 
               
               
                 213872_at 
                 BE465032 
                 C6orf62 
                 chromosome 6 open reading frame 62 
                 6p22.2 
                 −1.75 
                 0.00014 
               
               
                 218396_at 
                 NM_017684 
                 VPS13C 
                 vacuolar protein sorting 13C (yeast) 
                 15q22.2 
                 −1.79 
                 0.00002 
               
               
                 209007_s_at 
                 AF267856 
                 NPD014 
                 NPD014 protein 
                 1p36.13-p35.1 
                 −1.80 
                 0.00001 
               
               
                 201218_at 
                 N23018 
                 CTBP2 
                 C-terminal binding protein 2 
                 10q26.13 
                 −1.86 
                 0.00003 
               
               
                 203113_s_at 
                 NM_001960 
                 EEF1D 
                 eukaryotic translation elongation factor 1 delta 
                 8q24.3 
                 −1.86 
                 0.00118 
               
               
                   
                   
                   
                 (guanine nucleotide exchange protein) 
               
               
                 202663_at 
                 AI005043 
                 WASPIP 
                 Wiskott-Aldrich syndrome protein interacting protein 
                 2q31.1 
                 −1.89 
                 0.00001 
               
               
                 215646_s_at 
                 R94644 
                 CSPG2 
                 chondroitin sulfate proteoglycan 2 (versican) 
                 5q14.3 
                 −1.91 
                 0.00008 
               
               
                 202230_s_at 
                 NM_006387 
                 CHERP 
                 calcium homeostasis endoplasmic reticulum protein 
                 19p13.1 
                 −1.94 
                 0.00001 
               
               
                 201798_s_at 
                 NM_013451 
                 FER1L3 
                 fer-1-like 3, myoferlin ( C. elegans ) 
                 10q24 
                 −1.95 
                 0.00001 
               
               
                 212070_at 
                 AL554008 
                 GPR56 
                 G protein-coupled receptor 56 
                 16q13 
                 −2.02 
                 0.00001 
               
               
                 204516_at 
                 BG390306 
                 ATXN7 
                 ataxin 7 
                 3p21.1-p12 
                 −2.05 
                 0.00001 
               
               
                 214683_s_at 
                 AI251890 
                 CLK1 
                 CDC-like kinase 1 
                 2q33 
                 −2.07 
                 0.00002 
               
               
                 201088_at 
                 NM_002266 
                 KPNA2 
                 karyopherin alpha 2 (RAG cohort 1, importin alpha 1) 
                 17q23.1-q23.3 
                 −2.08 
                 0.00002 
               
               
                 208810_at 
                 AF080569 
                 DNAJB6 
                 DnaJ (Hsp40) homolog, subfamily B, member 6 
                 7q36.3 
                 −2.09 
                 0.00001 
               
               
                 211929_at 
                 AA527502 
                 HNRPA3 
                 heterogeneous nuclear ribonucleoprotein A3 
                 2q31.2 
                 −2.12 
                 0.00004 
               
               
                 213906_at 
                 AW592266 
                 MYBL1 
                 v-myb myeloblastosis viral oncogene homolog (avian)-like 1 
                 8q22 
                 −2.22 
                 0.00020 
               
               
                 203132_at 
                 NM_000321 
                 RB1 
                 retinoblastoma 1 (including osteosarcoma) 
                 13q14.2 
                 −2.46 
                 0.00005 
               
               
                 209006_s_at 
                 AF247168 
                 NPD014 
                 NPD014 protein 
                 1p36.13-p35.1 
                 −2.67 
                 0.00001 
               
               
                 221768_at 
                 AV705803 
                 SFPQ 
                 splicing factor proline/glutamine rich (polypyrimidine tract 
                 1p34.3 
                 −2.73 
                 0.00051 
               
               
                   
                   
                   
                 binding protein associated) 
               
               
                 202817_s_at 
                 NM_005637 
                 SS18 
                 synovial sarcoma translocation, chromosome 18 
                 18q11.2 
                 −7.24 
                 0.00002