CoMEt: A Statistical Approach to Identify Combinations of Mutually Exclusive Alterations in Cancer
summary
CoMEt introduces a contingency-table score and an algorithm that computes an exact tail p-value for mutual exclusivity in k-gene sets by enumerating only tail tables and using approximations when appropriate, then uses MCMC sampling to estimate co-occurrence frequencies and outputs a marginal probability graph from which high-weight exclusive modules are extracted; on TCGA glioblastoma it recovers modules covering ~90% and ~55% of samples and outperforms Multi-Dendrix and Mutex on simulations.
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chapters (10)
- 0:00Intro
- 0:14Driver mutations target pathways
- 3:12Motivation for statistical score Most frequently mutated genes can dominate the mutual exclusivity signal.
- 4:39Score a combination of k = 3 genes
- 5:21Statistical score for sets of any size k
- 5:34Computing exact test can be expensive
- 7:15Patients have alterations in multiple pathways
- 9:10COMEt results on TCGA Glioblastoma (GBM)
- 11:16COMEt analysis of subtype-specific mutations
- 12:46COMEt results on TCGA breast cancer (BRCA)
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