{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:37:47Z","timestamp":1791279467938,"version":"4.1.0"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1490,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: A current challenge in understanding cancer processes is to pinpoint which mutations influence the onset and progression of disease. Toward this goal, we describe a method called PARADIGM-SHIFT that can predict whether a mutational event is neutral, gain-or loss-of-function in a tumor sample. The method uses a belief-propagation algorithm to infer gene activity from gene expression and copy number data in the context of a set of pathway interactions.<\/jats:p>\n               <jats:p>Results: The method was found to be both sensitive and specific on a set of positive and negative controls for multiple cancers for which pathway information was available. Application to the Cancer Genome Atlas glioblastoma, ovarian and lung squamous cancer datasets revealed several novel mutations with predicted high impact including several genes mutated at low frequency suggesting the approach will be complementary to current approaches that rely on the prevalence of events to reach statistical significance.<\/jats:p>\n               <jats:p>Availability: All source code is available at the github repository http:github.org\/paradigmshift.<\/jats:p>\n               <jats:p>Contact: \u00a0jstuart@soe.ucsc.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts402","type":"journal-article","created":{"date-parts":[[2012,9,7]],"date-time":"2012-09-07T20:35:22Z","timestamp":1347050122000},"page":"i640-i646","source":"Crossref","is-referenced-by-count":91,"title":["PARADIGM-SHIFT predicts the function of mutations in multiple cancers using pathway impact analysis"],"prefix":"10.1093","volume":"28","author":[{"given":"Sam","family":"Ng","sequence":"first","affiliation":[{"name":"1 Department of Biomolecular Engineering and CBSE, University of California Santa Cruz, 95064 Santa Cruz"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Collisson","sequence":"additional","affiliation":[{"name":"2 School of Medicine, University of California San Francisco, San Francisco, 94143 CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Sokolov","sequence":"additional","affiliation":[{"name":"1 Department of Biomolecular Engineering and CBSE, University of California Santa Cruz, 95064 Santa Cruz"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Goldstein","sequence":"additional","affiliation":[{"name":"1 Department of Biomolecular Engineering and CBSE, University of California Santa Cruz, 95064 Santa Cruz"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"Gonzalez-Perez","sequence":"additional","affiliation":[{"name":"3 Parc de Recerca Biomedica de Barcelona, E-08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Lopez-Bigas","sequence":"additional","affiliation":[{"name":"4 Universitat Pompeu Fabra, E-08002 Barcelona, Spain"},{"name":"5 Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), E-08010 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Benz","sequence":"additional","affiliation":[{"name":"6 Buck Institute for Aging, Unit for Christopher Benz is \u201cCancer Therapeutics Program\u201d 94945 Novato"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Haussler","sequence":"additional","affiliation":[{"name":"1 Department of Biomolecular Engineering and CBSE, University of California Santa Cruz, 95064 Santa Cruz"},{"name":"7 Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, 95064 CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Stuart","sequence":"additional","affiliation":[{"name":"1 Department of Biomolecular Engineering and CBSE, University of California Santa Cruz, 95064 Santa Cruz"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,3]]},"reference":[{"key":"2023012513074518700_B1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations'","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. 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