RT Journal Article SR Electronic T1 Causal interactions from proteomic profiles: molecular data meets pathway knowledge JF bioRxiv FD Cold Spring Harbor Laboratory SP 258855 DO 10.1101/258855 A1 Babur, Özgün A1 Luna, Augustin A1 Korkut, Anil A1 Durupinar, Funda A1 Siper, Metin Can A1 Dogrusoz, Ugur A1 Aslan, Joseph E. A1 Sander, Chris A1 Demir, Emek YR 2018 UL http://biorxiv.org/content/early/2018/05/21/258855.abstract AB Measurement of changes in protein levels and in post-translational modifications, such as phosphorylation, can be highly informative about the phenotypic consequences of genetic differences or about the dynamics of cellular processes. Typically, such proteomic profiles are interpreted intuitively or by simple correlation analysis. Here, we present a computational method to generate causal explanations for proteomic profiles using prior mechanistic knowledge in the literature, as recorded in cellular pathway maps. To demonstrate its potential, we use this method to analyze the cascading events after EGF stimulation of a cell line, to discover new pathways in platelet activation, to identify influential regulators of oncoproteins in breast cancer, to describe signaling characteristics in predefined subtypes of ovarian and breast cancers, and to highlight which pathway relations are most frequently activated across 32 cancer types. Causal pathway analysis, that combines molecular profiles with prior biological knowledge captured in computational form, may become a powerful discovery tool as the amount and quality of cellular profiling rapidly expands. The method is freely available at http://causalpath.org.