{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T23:04:12Z","timestamp":1769641452284,"version":"3.49.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Sapere Aude","award":["12-126439"],"award-info":[{"award-number":["12-126439"]}]},{"name":"JSP"},{"DOI":"10.13039\/100012774","name":"Innovation Fund Denmark","doi-asserted-by":"crossref","award":["10-092320\/DSF"],"award-info":[{"award-number":["10-092320\/DSF"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JSP"},{"name":"Independent Research Fund Denmark","award":["7016-00379"],"award-info":[{"award-number":["7016-00379"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Understanding the mutational processes that act during cancer development is a key topic of cancer biology. Nevertheless, much remains to be learned, as a complex interplay of processes with dependencies on a range of genomic features creates highly heterogeneous cancer genomes. Accurate driver detection relies on unbiased models of the mutation rate that also capture rate variation from uncharacterized sources.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we analyse patterns of observed-to-expected mutation counts across 505 whole cancer genomes, and find that genomic features missing from our mutation-rate model likely operate on a megabase length scale. We extend our site-specific model of the mutation rate to include the additional variance from these sources, which leads to robust significance evaluation of candidate cancer drivers. We thus present ncdDetect v.2, with greatly improved cancer driver detection specificity. Finally, we show that ranking candidates by their posterior mean value of their effect sizes offers an equivalent and more computationally efficient alternative to ranking by their P-values.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>ncdDetect v.2 is implemented as an R-package and is freely available at http:\/\/github.com\/TobiasMadsen\/ncdDetect2<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty511","type":"journal-article","created":{"date-parts":[[2018,6,24]],"date-time":"2018-06-24T19:09:27Z","timestamp":1529867367000},"page":"189-199","source":"Crossref","is-referenced-by-count":7,"title":["ncdDetect2: improved models of the site-specific mutation rate in cancer and driver detection with robust significance evaluation"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-0461","authenticated-orcid":false,"given":"Malene","family":"Juul","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N, Denmark"},{"name":"Bioinformatics Research Centre, Aarhus University, C.F. Mollers Alle 8, DK-8000 Aarhus C, Denmark"}]},{"given":"Tobias","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N, Denmark"},{"name":"Bioinformatics Research Centre, Aarhus University, C.F. Mollers Alle 8, DK-8000 Aarhus C, Denmark"}]},{"given":"Qianyun","family":"Guo","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Centre, Aarhus University, C.F. Mollers Alle 8, DK-8000 Aarhus C, Denmark"}]},{"given":"Johanna","family":"Bertl","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N, Denmark"}]},{"given":"Asger","family":"Hobolth","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Centre, Aarhus University, C.F. 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