NeST Map - Main Model

The NeST (Nested Systems in Tumors) map is a hierarchy of 395 protein systems that are recurrently mutated in one or more cancer types. It provides a resource of cancer mechanisms under selection for somatic mutations and captures canonical cancer pathways and protein complexes, along with novel protein assemblies on which mutations unexpectedly converge. NeST was assembled by creating an Integrated Protein Network combining evidence of interactions of five major data types: physical protein-protein interactions (novel and previously known), mRNA co-expression, protein co-expression, sequence similarity, and genetic co-dependence. Multiscale community detection was then applied to the network to detect protein communities (a.k.a. "systems") at different size resolutions. Communities detected at small size resolutions can overlap with one another and nest within communities at larger size resolutions, resulting in a hierarchy of systems. Finally, a statistical model called HiSig was developed to identify the systems on which cancer mutations significantly converge, yielding the NeST Systems Map of 395 systems.