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Functional Categories Associated with Clusters of Genes That Are Co-Expressed across the NCI-60 Cancer Cell Lines

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  • Barry R Zeeberg
  • William Reinhold
  • René Snajder
  • Gerhard G Thallinger
  • John N Weinstein
  • Kurt W Kohn
  • Yves Pommier

Abstract

Background: The NCI-60 is a panel of 60 diverse human cancer cell lines used by the U.S. National Cancer Institute to screen compounds for anticancer activity. In the current study, gene expression levels from five platforms were integrated to yield a single composite transcriptome profile. The comprehensive and reliable nature of that dataset allows us to study gene co-expression across cancer cell lines. Methodology/Principal Findings: Hierarchical clustering revealed numerous clusters of genes in which the genes co-vary across the NCI-60. To determine functional categorization associated with each cluster, we used the Gene Ontology (GO) Consortium database and the GoMiner tool. GO maps genes to hierarchically-organized biological process categories. GoMiner can leverage GO to perform ontological analyses of gene expression studies, generating a list of significant functional categories. Conclusions/Significance: GoMiner analysis revealed many clusters of coregulated genes that are associated with functional groupings of GO biological process categories. Notably, those categories arising from coherent co-expression groupings reflect cancer-related themes such as adhesion, cell migration, RNA splicing, immune response and signal transduction. Thus, these clusters demonstrate transcriptional coregulation of functionally-related genes.

Suggested Citation

  • Barry R Zeeberg & William Reinhold & René Snajder & Gerhard G Thallinger & John N Weinstein & Kurt W Kohn & Yves Pommier, 2012. "Functional Categories Associated with Clusters of Genes That Are Co-Expressed across the NCI-60 Cancer Cell Lines," PLOS ONE, Public Library of Science, vol. 7(1), pages 1-10, January.
  • Handle: RePEc:plo:pone00:0030317
    DOI: 10.1371/journal.pone.0030317
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    1. Levi A. Garraway & Hans R. Widlund & Mark A. Rubin & Gad Getz & Aaron J. Berger & Sridhar Ramaswamy & Rameen Beroukhim & Danny A. Milner & Scott R. Granter & Jinyan Du & Charles Lee & Stephan N. Wagne, 2005. "Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma," Nature, Nature, vol. 436(7047), pages 117-122, July.
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