A new correlation clustering method for cancer mutation analysis.

Abstract

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. 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. 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.