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A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence

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 Ob...

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Autores principales: Canisius, Sander, Martens, John W. M., Wessels, Lodewyk F. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5162102/
https://www.ncbi.nlm.nih.gov/pubmed/27986087
http://dx.doi.org/10.1186/s13059-016-1114-x
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author Canisius, Sander
Martens, John W. M.
Wessels, Lodewyk F. A.
author_facet Canisius, Sander
Martens, John W. M.
Wessels, Lodewyk F. A.
author_sort Canisius, Sander
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1114-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-51621022016-12-23 A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence Canisius, Sander Martens, John W. M. Wessels, Lodewyk F. A. Genome Biol Method 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1114-x) contains supplementary material, which is available to authorized users. BioMed Central 2016-12-16 /pmc/articles/PMC5162102/ /pubmed/27986087 http://dx.doi.org/10.1186/s13059-016-1114-x Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Method
Canisius, Sander
Martens, John W. M.
Wessels, Lodewyk F. A.
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
title_full A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence
title_fullStr A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence
title_full_unstemmed A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence
title_short A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence
title_sort novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5162102/
https://www.ncbi.nlm.nih.gov/pubmed/27986087
http://dx.doi.org/10.1186/s13059-016-1114-x
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