PT  - JOURNAL ARTICLE
AU  - Michael Schubert
AU  - Bertram Klinger
AU  - Martina Klünemann
AU  - Mathew J Garnett
AU  - Nils Blüthgen
AU  - Julio Saez-Rodriguez
TI  - Perturbation-response genes reveal signaling footprints in cancer gene expression
AID  - 10.1101/065672
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 065672
4099  - http://biorxiv.org/content/early/2016/08/28/065672.short
4100  - http://biorxiv.org/content/early/2016/08/28/065672.full
AB  - Aberrant cell signaling is known to cause cancer and many other diseases, as well as a focus of treatment. A common approach is to infer its activity on the level of pathways using 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 existing 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 more accurately infers pathway activity from gene expression than other methods.