Network-Based Coverage of Mutational Profiles Reveals Cancer Genes. Author Borislav Hristov, Mona Singh Publication Year 2017 Type Journal Article Abstract A central goal in cancer genomics is to identify the somatic alterations that underpin tumor initiation and progression. While commonly mutated cancer genes are readily identifiable, those that are rarely mutated across samples are difficult to distinguish from the large numbers of other infrequently mutated genes. We introduce a method, nCOP, that considers per-individual mutational profiles within the context of protein-protein interaction networks in order to identify small connected subnetworks of genes that, while not individually frequently mutated, comprise pathways that are altered across (i.e., "cover") a large fraction of individuals. By analyzing 6,038 samples across 24 different cancer types, we demonstrate that nCOP is highly effective in identifying cancer genes, including those with low mutation frequencies. Overall, our work demonstrates that combining per-individual mutational information with interaction networks is a powerful approach for tackling the mutational heterogeneity observed across cancers. Keywords Humans, Computational Biology, Mutation, Genomics, Algorithms, Computer Simulation, Protein Interaction Maps, Mutation Rate, Neoplasms, Gene Regulatory Networks, Disease Progression, Oncogenes Journal Cell Syst Volume 5 Issue 3 Pages 221-229.e4 Date Published 2017 Sep 27 ISSN Number 2405-4712 DOI 10.1016/j.cels.2017.09.003 Alternate Journal Cell Syst PMCID PMC5997485 PMID 28957656 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML