Network-Based Coverage of Mutational Profiles Reveals Cancer Genes.

TitleNetwork-Based Coverage of Mutational Profiles Reveals Cancer Genes.
Publication TypeJournal Article
Year of Publication2017
AuthorsHristov, BH, Singh, M
JournalCell Syst
Date Published2017 09 27
KeywordsAlgorithms, Computational Biology, Computer Simulation, Disease Progression, Gene Regulatory Networks, Genomics, Humans, Mutation, Mutation Rate, Neoplasms, Oncogenes, Protein Interaction Maps

<p>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.</p>

Alternate JournalCell Syst
PubMed ID28957656
PubMed Central IDPMC5997485
Grant ListR01 CA208148 / CA / NCI NIH HHS / United States