Ontology highlight
ABSTRACT: Motivation
Cancer genomes exhibit a large number of different alterations that affect many genes in a diverse manner. An improved understanding of the generative mechanisms behind the mutation rules and their influence on gene community behavior is of great importance for the study of cancer.Results
To expand our capability to analyze combinatorial patterns of cancer alterations, we developed a rigorous methodology for cancer mutation pattern discovery based on a new, constrained form of correlation clustering. Our new algorithm, named C3 (Cancer Correlation Clustering), leverages mutual exclusivity of mutations, patient coverage and driver network concentration principles. To test C3, we performed a detailed analysis on TCGA breast cancer and glioblastoma data and showed that our algorithm outperforms the state-of-the-art CoMEt method in terms of discovering mutually exclusive gene modules and identifying biologically relevant driver genes. The proposed agnostic clustering method represents a unique tool for efficient and reliable identification of mutation patterns and driver pathways in large-scale cancer genomics studies, and it may also be used for other clustering problems on biological graphs.Availability and implementation
The source code for the C3 method can be found at https://github.com/jackhou2/C3 CONTACTS: jianma@cs.cmu.edu or milenkov@illinois.eduSupplementary information: Supplementary data are available at Bioinformatics online.
SUBMITTER: Hou JP
PROVIDER: S-EPMC6078169 | biostudies-literature | 2016 Dec
REPOSITORIES: biostudies-literature
Hou Jack P JP Emad Amin A Puleo Gregory J GJ Ma Jian J Milenkovic Olgica O
Bioinformatics (Oxford, England) 20160818 24
<h4>Motivation</h4>Cancer genomes exhibit a large number of different alterations that affect many genes in a diverse manner. An improved understanding of the generative mechanisms behind the mutation rules and their influence on gene community behavior is of great importance for the study of cancer.<h4>Results</h4>To expand our capability to analyze combinatorial patterns of cancer alterations, we developed a rigorous methodology for cancer mutation pattern discovery based on a new, constrained ...[more]