IDM-SPS: Identifying driver module with somatic mutation, PPI network and subcellular localization

Abstract

Mutation profiles together with prior knowledge such as interactions between genes/proteins provide abundant critical information for the identification of driver modules, which is very important for analyzing mutational heterogeneity in human cancers. Due to the negative effects of inevitable false positive interactions in the PPI network, subcellular localization data are exerted to filter out them firstly, and somatic mutation profiles are used to weight the retained interactions. Five novel recombination operators are introduced basing on the vertex degrees and the edge weights in the PPI network, and a parthenogenetic algorithm is devised for solving the presented identification model which takes into account network connectivity, mutual exclusivity, coverage, and hops between genes within a module. Extensive experimental results indicate that compared with two state-of-the-art computational methods Hotnet2 and MEXCOwalk, the proposed method exhibits competitive performance in most cases in terms of recovering known cancer genes, providing modules that have satisfied coverage and mutual exclusivity, and are enriched for mutations in specific cancer types. Many identified gene sets are involved in known signaling pathways, most of the implicated genes are oncogenes or tumor suppressors previously reported in the literature. In addition, the proposed method does identify many cancer related genes missed by methods Hotnet2 and MEXCOwalk, including some recognized genes covering many types of cancers but having low mutation frequency.