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         headline:Gene expression phenotypic models that predict the activity of oncogenic pathways
         description:High-density DNA microarrays measure expression of large numbers of genes in one assay. The ability to find underlying structure in complex gene expression data sets and rigorously test association of that structure with biological conditions is essential to developing multi-faceted views of the gene activity that defines cellular phenotype. We sought to connect features of gene expression data with biological hypotheses by integrating 'metagene' patterns from DNA microarray experiments in the characterization and prediction of oncogenic phenotypes. We applied these techniques to the analysis of regulatory pathways controlled by the genes HRAS (Harvey rat sarcoma viral oncogene homolog), MYC (myelocytomatosis viral oncogene homolog) and E2F1, E2F2 and E2F3 (encoding E2F transcription factors 1, 2 and 3, respectively). The phenotypic models accurately predict the activity of these pathways in the context of normal cell proliferation. Moreover, the metagene models trained with gene expression patterns evoked by ectopic production of Myc or Ras proteins in primary tissue culture cells properly predict the activity of in vivo tumor models that result from deregulation of the MYC or HRAS pathways. We conclude that these gene expression phenotypes have the potential to characterize the complex genetic alterations that typify the neoplastic state, whether in vitro or in vivo, in a way that truly reflects the complexity of the regulatory pathways that are affected.
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            type:Organization
            name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University
            address:
               name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
               type:PostalAddress
            type:Organization
      name:Mark Kloos
      affiliation:
            name:Duke University
            address:
               name:Department of Molecular Genetics and Microbiology, Duke University, Durham, USA
               type:PostalAddress
            type:Organization
      name:Mark D'Amico
      affiliation:
            name:Lombardi Comprehensive Cancer Center, Georgetown University
            address:
               name:Lombardi Comprehensive Cancer Center, Georgetown University, Washington, USA
               type:PostalAddress
            type:Organization
      name:Richard G Pestell
      affiliation:
            name:Lombardi Comprehensive Cancer Center, Georgetown University
            address:
               name:Lombardi Comprehensive Cancer Center, Georgetown University, Washington, USA
               type:PostalAddress
            type:Organization
      name:Mike West
      affiliation:
            name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University
            address:
               name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
               type:PostalAddress
            type:Organization
            name:Institute of Statistics and Decision Sciences, Duke University
            address:
               name:Institute of Statistics and Decision Sciences, Duke University, Durham, USA
               type:PostalAddress
            type:Organization
      name:Joseph R Nevins
      affiliation:
            name:Duke University
            address:
               name:Department of Molecular Genetics and Microbiology, Duke University, Durham, USA
               type:PostalAddress
            type:Organization
            name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University
            address:
               name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
               type:PostalAddress
            type:Organization
            name:Center for Genome Technology, Duke Institute for Genome Sciences and Policy, Duke University
            address:
               name:Center for Genome Technology, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
               type:PostalAddress
            type:Organization
            name:Howard Hughes Medical Institute, Duke University Medical Center
            address:
               name:Howard Hughes Medical Institute, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Molecular Genetics and Microbiology, Duke University, Durham, USA
      name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
      name:Department of Molecular Genetics and Microbiology, Duke University, Durham, USA
      name:Division of Pharmacology, National Institute of Health Sciences 1-18-1, Kamiyoga, Setagaya-Ku Tokyo, Japan
      name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
      name:Institute of Statistics and Decision Sciences, Duke University, Durham, USA
      name:Department of Molecular Genetics and Microbiology, Duke University, Durham, USA
      name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
      name:Center for Genome Technology, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
      name:Department of Molecular Genetics and Microbiology, Duke University, Durham, USA
      name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
      name:Department of Molecular Genetics and Microbiology, Duke University, Durham, USA
      name:Lombardi Comprehensive Cancer Center, Georgetown University, Washington, USA
      name:Lombardi Comprehensive Cancer Center, Georgetown University, Washington, USA
      name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
      name:Institute of Statistics and Decision Sciences, Duke University, Durham, USA
      name:Department of Molecular Genetics and Microbiology, Duke University, Durham, USA
      name:Computational and Applied Genomics Program, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
      name:Center for Genome Technology, Duke Institute for Genome Sciences and Policy, Duke University, Durham, USA
      name:Howard Hughes Medical Institute, Duke University Medical Center, Durham, USA
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