Perturbation-response genes reveal signaling footprints in cancer gene expression

Michael Schubert1, Bertram Klinger2,3, Martina Klünemann2,3

  • 1European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, CB10 1SD, UK.

Nature Communications
|January 4, 2018
PubMed

Insights

PROGENy infers pathway activity from gene expression, overcoming limitations of current methods. This novel approach aids in understanding cancer, identifying drug targets, and predicting patient survival by analyzing pathway responsive genes.

Area of Science:

  • Molecular Biology
  • Systems Biology
  • Bioinformatics

Background:

  • Aberrant cell signaling drives cancer and diseases, making it a key drug research target.
  • Current methods infer pathway activity from gene expression but ignore post-translational modifications and specific experimental conditions.

Purpose of the Study:

  • To introduce PROGENy, a novel method for inferring pathway activity from gene expression.
  • To overcome limitations of existing pathway inference methods, specifically post-translational modifications and condition-specific signatures.

Main Methods:

  • PROGENy leverages a large compendium of perturbation experiments.
  • It identifies a common core of Pathway RespOnsive GENes (PROGENy).
  • The method analyzes gene expression data to infer pathway activity.

Main Results:

  • PROGENy recovers the effects of known driver mutations.
  • It provides or improves markers for drug indications.
  • The method distinguishes between oncogenic and tumor suppressor pathways for patient survival prediction.

Conclusions:

  • PROGENy accurately infers pathway activity across diverse conditions.
  • This method offers a more robust approach to understanding cell signaling in disease.
  • PROGENy has significant implications for cancer research and therapeutic development.

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