TY - JOUR T1 - Perturbation-response genes reveal signaling footprints in cancer gene expression JF - bioRxiv DO - 10.1101/065672 SP - 065672 AU - Michael Schubert AU - Bertram Klinger AU - Martina Klünemann AU - Mathew J Garnett AU - Nils Blüthgen AU - Julio Saez-Rodriguez Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/08/28/065672.abstract N2 - 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. ER -