RT Journal Article
SR Electronic
T1 Perturbation-response genes reveal signaling footprints in cancer gene expression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 065672
DO 10.1101/065672
A1 Michael Schubert
A1 Bertram Klinger
A1 Martina Klünemann
A1 Mathew J Garnett
A1 Nils Blüthgen
A1 Julio Saez-Rodriguez
YR 2016
UL http://biorxiv.org/content/early/2016/08/28/065672.abstract
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.