Perturbation-response genes reveal signaling footprints in cancer gene expression

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 stro