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Perturbation-response genes reveal signaling footprints in cancer gene expression

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Item Type:Article
Title:Perturbation-response genes reveal signaling footprints in cancer gene expression
Creators Name:Schubert, M., Klinger, B., Klünemann, M., Sieber, A., Uhlitz, F., Sauer, S., Garnett, M.J., Blüthgen, N. and Saez-Rodriguez, J.
Abstract:Aberrant cell signaling can cause cancer and other diseases and is a focal point of drug research. A common approach is to infer signaling activity of pathways from gene expression. However, mapping gene expression to pathway components disregards the effect of post-translational modifications, and downstream signatures represent very specific experimental conditions. Here we present PROGENy, a method that overcomes both limitations by leveraging a large compendium of publicly available perturbation experiments to yield a common core of Pathway RespOnsive GENes. Unlike pathway mapping methods, PROGENy can (i) recover the effect of known driver mutations, (ii) provide or improve strong markers for drug indications, and (iii) distinguish between oncogenic and tumor suppressor pathways for patient survival. Collectively, these results show that PROGENy accurately infers pathway activity from gene expression in a wide range of conditions.
Keywords:Cell Line, Tumor, Drug Resistance, Neoplasm, Gene Expression, Genes, Neoplasm, Genomics, HEK293 Cells, Mutation, Neoplasms
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:20
Date:2 January 2018
Official Publication:https://doi.org/10.1038/s41467-017-02391-6
PubMed:View item in PubMed

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