Print Email Facebook Twitter A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence Title A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence Author Canisius, Sander (Netherlands Cancer Institute) Wessels, L.F.A. (TU Delft Pattern Recognition and Bioinformatics; Netherlands Cancer Institute) Martens, John W. M. (Erasmus MC) Date 2016 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. Subject Mutual exclusivityCo-occurrenceComputational biology To reference this document use: http://resolver.tudelft.nl/uuid:fdbd4f89-050e-4502-9718-70771d467bd5 DOI https://doi.org/10.1186/s13059-016-1114-x ISSN 1474-760X Source Genome Biology (Online), 17 (261), 1-17 Part of collection Institutional Repository Document type journal article Rights © 2016 Sander Canisius, L.F.A. Wessels, John W. M. Martens Files PDF art_3A10.1186_2Fs13059_01 ... 1114_x.pdf 1.28 MB Close viewer /islandora/object/uuid:fdbd4f89-050e-4502-9718-70771d467bd5/datastream/OBJ/view