Network modeling of the transcriptional effects of copy number aberrations in glioblastoma

Rebecka Jörnsten, Tobias Abenius, Teresia Kling, Linna Schmidt, Erik Johansson, Torbjrn E.M. Nordling, Bodil Nordlander, Chris Sander, Peter Gennemark, Keiko Funa, Björn Nilsson, Linda Lindahl, Sven Nelander

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71 引文 斯高帕斯(Scopus)

摘要

DNA copy number aberrations (CNAs) are a hallmark of cancer genomes. However, little is known about how such changes affect global gene expression. We develop a modeling framework, EPoC (Endogenous Perturbation analysis of Cancer), to (1) detect disease-driving CNAs and their effect on target mRNA expression, and to (2) stratify cancer patients into long- and short-term survivors. Our method constructs causal network models of gene expression by combining genome-wide DNA- and RNA-level data. Prognostic scores are obtained from a singular value decomposition of the networks. By applying EPoC to glioblastoma data from The Cancer Genome Atlas consortium, we demonstrate that the resulting network models contain known disease-relevant hub genes, reveal interesting candidate hubs, and uncover predictors of patient survival. Targeted validations in four glioblastoma cell lines support selected predictions, and implicate the p53-interacting protein Necdin in suppressing glioblastoma cell growth. We conclude that large-scale network modeling of the effects of CNAs on gene expression may provide insights into the biology of human cancer. Free software in MATLAB and R is provided.

原文English
文章編號486
期刊Molecular Systems Biology
7
DOIs
出版狀態Published - 2011

All Science Journal Classification (ASJC) codes

  • 生物化學、遺傳與分子生物學 (全部)
  • 免疫學與微生物學 (全部)
  • 農業與生物科學 (全部)
  • 應用數學

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