Identification of driver modules in pan-cancer via coordinating coverage and exclusivity

Abstract

It is widely accepted that cancer is driven by accumulated somatic mutations during the lifetime of an individual. Cancer mutations may target relatively small number of cell functional modules. The heterogeneity in different cancer patients makes it difficult to identify driver mutations or functional modules related to cancer. It is biologically desired to be capable of identifying cancer pathway modules through coordination between coverage and exclusivity. There have been a few approaches developed for this purpose, but they all have limitations in practice due to their computational complexity and prediction accuracy. We present a network based approach, CovEx, to predict the specific patient oriented modules by 1) discovering candidate modules for each considered gene, 2) extracting significant candidates by harmonizing coverage and exclusivity and, 3) further selecting the patient oriented modules based on a set cover model. Applying CovEx to pan-cancer datasets spanning 12 cancer types collecting from public database TCGA, it demonstrates significant superiority over the current leading competitors in performance. It is published under GNU GENERAL PUBLIC LICENSE and the source code is available at: https://sourceforge.net/projects/cancer-pathway/files/.