Gene expression phenotypic models that predict the activity of oncogenic pathways

Erich Huang, Seiichi Ishida, Jennifer L Clarke, Holly Dressman, Andrea Bild, Mark Kloos, Mark D'Amico, Richard G. Pestell, Mike West, Joseph R. Nevins

Research output: Contribution to journalArticle

199 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)226-230
Number of pages5
JournalNature Genetics
Volume34
Issue number2
DOIs
StatePublished - Jun 1 2003

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Gene Expression
Oligonucleotide Array Sequence Analysis
Phenotype
Oncogenes
E2F3 Transcription Factor
E2F2 Transcription Factor
E2F1 Transcription Factor
Genes
ras Proteins
Primary Cell Culture
Sarcoma
Cell Proliferation
Neoplasms
In Vitro Techniques
Datasets

ASJC Scopus subject areas

  • Genetics

Cite this

Huang, E., Ishida, S., Clarke, J. L., Dressman, H., Bild, A., Kloos, M., ... Nevins, J. R. (2003). Gene expression phenotypic models that predict the activity of oncogenic pathways. Nature Genetics, 34(2), 226-230. https://doi.org/10.1038/ng1167

Gene expression phenotypic models that predict the activity of oncogenic pathways. / Huang, Erich; Ishida, Seiichi; Clarke, Jennifer L; Dressman, Holly; Bild, Andrea; Kloos, Mark; D'Amico, Mark; Pestell, Richard G.; West, Mike; Nevins, Joseph R.

In: Nature Genetics, Vol. 34, No. 2, 01.06.2003, p. 226-230.

Research output: Contribution to journalArticle

Huang, E, Ishida, S, Clarke, JL, Dressman, H, Bild, A, Kloos, M, D'Amico, M, Pestell, RG, West, M & Nevins, JR 2003, 'Gene expression phenotypic models that predict the activity of oncogenic pathways', Nature Genetics, vol. 34, no. 2, pp. 226-230. https://doi.org/10.1038/ng1167
Huang, Erich ; Ishida, Seiichi ; Clarke, Jennifer L ; Dressman, Holly ; Bild, Andrea ; Kloos, Mark ; D'Amico, Mark ; Pestell, Richard G. ; West, Mike ; Nevins, Joseph R. / Gene expression phenotypic models that predict the activity of oncogenic pathways. In: Nature Genetics. 2003 ; Vol. 34, No. 2. pp. 226-230.
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