Gene pathways and subnetworks distinguish between major glioma subtypes and elucidate potential underlying biology

Stefan Wuchty, Alice Zhang, Jennifer Walling, Susie Ahn, Aiguo Li, Martha Quezado, Carl Oberholtzer, Jean Claude Zenklusen, Howard A. Fine

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Molecular diagnostic tools are increasingly being used in an attempt to classify primary human brain tumors more accurately. While methods that are based on the analysis of individual gene expression prove to be useful for diagnostic purposes, they are devoid of biological significance since tumorgenesis is a concerted deregulation of multiple pathways rather than single genes. In a proof of concept, we utilize two large clinical data sets and show that the elucidation of enriched pathways and small differentially expressed sub-networks of protein interactions allow a reliable classification of glioblastomas and oligodendrogliomas. Applying a feature selection method, we observe that an optimized subset of pathways and subnetworks significantly improves the prediction accuracy. By determining the enrichment of altered genes in pathways and subnetworks we show that optimized subsets of genes rarely seem to be a target of genomic alteration. Our results suggest that groups of genes play a decisive role for the phenotype of the underlying tumor samples that can be utilized to reliably distinguish tumor types. In the absence of enrichment of genes that are genomically altered we assume that genetic changes largely exert an indirect rather than direct regulatory influence on a number of tumor-defining regulatory networks.

Original languageEnglish (US)
Pages (from-to)945-952
Number of pages8
JournalJournal of biomedical informatics
Volume43
Issue number6
DOIs
StatePublished - Dec 2010

Keywords

  • Classification
  • Gliomas
  • Pathways
  • Subnetworks

ASJC Scopus subject areas

  • Computer Science Applications
  • Health Informatics

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    Wuchty, S., Zhang, A., Walling, J., Ahn, S., Li, A., Quezado, M., Oberholtzer, C., Zenklusen, J. C., & Fine, H. A. (2010). Gene pathways and subnetworks distinguish between major glioma subtypes and elucidate potential underlying biology. Journal of biomedical informatics, 43(6), 945-952. https://doi.org/10.1016/j.jbi.2010.08.011