A new correlation clustering method for cancer mutation analysis

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.