A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence
Open Access
- 16 December 2016
- journal article
- method
- Published by Springer Science and Business Media LLC in Genome Biology
- Vol. 17 (1), 1-17
- https://doi.org/10.1186/s13059-016-1114-x
Abstract
In cancer, mutually exclusive or co-occurring somatic alterations across genes can suggest functional interactions. Existing tests for such patterns make the unrealistic assumption of identical gene alteration probabilities across tumors. We present Discrete Independence Statistic Controlling for Observations with Varying Event Rates (DISCOVER), a novel test that is more sensitive than other methods and controls its false positive rate. A pan-cancer analysis using DISCOVER finds no evidence for widespread co-occurrence, and most co-occurrences previously detected do not exceed expectation by chance. Many mutual exclusivities are identified involving well-known genes related to cell cycle and growth factor signaling, as well as lesser known regulators of Hedgehog signaling.Keywords
Funding Information
- Cancer Genomics Centre
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