Oncoprotein-specific molecular interaction maps (SigMaps) for cancer network analyses.

ABSTRACT: Tumor-specific elucidation of physical and functional oncoprotein interactions could improve tumorigenic mechanism characterization and therapeutic response prediction. Current interaction models and pathways, however, lack context specificity and are not oncoprotein specific. We introduce SigMaps as context-specific networks, comprising modulators, effectors and cognate binding-partners of a specific oncoprotein. SigMaps are reconstructed de novo by integrating diverse evidence sources-including protein structure, gene expression and mutational profiles-via the OncoSig machine learning framework. We first generated a KRAS-specific SigMap for lung adenocarcinoma, which recapitulated published KRAS biology, identified novel synthetic lethal proteins that were experimentally validated in thr

SUBMITTER: Broyde J 

PROVIDER: S-EPMC7878435 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature