RT Journal Article SR Electronic T1 Methods for detecting co-mutated pathways in cancer samples to inform treatment selection JF bioRxiv FD Cold Spring Harbor Laboratory SP 082552 DO 10.1101/082552 A1 Tingting Jiang A1 Uri Shaham A1 Fabio Parisi A1 Ruth Halaban A1 Anton Safonov A1 Harriet Kluger A1 Sherman Weissman A1 Joseph Chang A1 Yuval Kluger YR 2016 UL http://biorxiv.org/content/early/2016/10/22/082552.abstract AB Tumor genomes evolve through a selection of mutations. These mutations may complement each other to promote tumorigenesis. To better understand the functional interactions of different processes in cancer, we studied mutation data of a set of tumors and identified significantly co-mutated pathways. Fisher’s exact test is a standard approach that can be used to assess the significance of the joint dysregulation of pathways pairs across a patient population. We developed a robust test to identify co-occurrence using DNA mutations, which overcomes deficiencies of the Fisher’s exact test by taking into account the large variability in overall mutation load and sequencing depth. Applying our method to a study of six common cancer types, we identify enrichment of co-mutated signal transduction pathways such as IP3 synthesis and PI3K and pairs of co-mutated pathways involving other processes such as immunity and development. We observed enrichment of clonal co-mutation of the proteasome and apoptosis pathways in colorectal cancer, which suggests potential mechanisms for immune evasion.