{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:05:16Z","timestamp":1792800316382,"version":"4.5.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:00:00Z","timestamp":1602028800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:00:00Z","timestamp":1602028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Cancer Research UK Grand Challenge","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Performing a statistical test requires a null hypothesis. In cancer genomics, a key challenge is the fast generation of accurate somatic mutational landscapes that can be used as a realistic null hypothesis for making biological discoveries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here we present SigProfilerSimulator, a powerful tool that is capable of simulating the mutational landscapes of thousands of cancer genomes at different resolutions within seconds. Applying SigProfilerSimulator to 2144 whole-genome sequenced cancers reveals: (i) that most doublet base substitutions are not due to two adjacent single base substitutions but likely occur as single genomic events; (ii) that an extended sequencing context of \u00b1\u20092\u00a0bp is required to more completely capture the patterns of substitution mutational signatures in human cancer; (iii) information on false-positive discovery rate of commonly used bioinformatics tools for detecting driver genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      SigProfilerSimulator\u2019s breadth of features allows one to construct a tailored null hypothesis and use it for evaluating the accuracy of other bioinformatics tools or for downstream statistical analysis for biological discoveries. SigProfilerSimulator is freely available at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/AlexandrovLab\/SigProfilerSimulator\">https:\/\/github.com\/AlexandrovLab\/SigProfilerSimulator<\/jats:ext-link>\n                      with an extensive documentation at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/osf.io\/usxjz\/wiki\/home\/\">https:\/\/osf.io\/usxjz\/wiki\/home\/<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12859-020-03772-3","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T05:05:57Z","timestamp":1602047157000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Generating realistic null hypothesis of cancer mutational landscapes using SigProfilerSimulator"],"prefix":"10.1186","volume":"21","author":[{"given":"Erik N.","family":"Bergstrom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u00f1igo","family":"Martincorena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-4515","authenticated-orcid":false,"given":"Ludmil B.","family":"Alexandrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,7]]},"reference":[{"issue":"2","key":"3772_CR1","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1093\/bioinformatics\/btq630","volume":"27","author":"A Youn","year":"2011","unstructured":"Youn A, Simon R. Identifying cancer driver genes in tumor genome sequencing studies. Bioinformatics. 2011;27(2):175\u201381.","journal-title":"Bioinformatics"},{"issue":"5797","key":"3772_CR2","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1126\/science.1133427","volume":"314","author":"T Sjoblom","year":"2006","unstructured":"Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, et al. The consensus coding sequences of human breast and colorectal cancers. Science. 2006;314(5797):268\u201374.","journal-title":"Science"},{"issue":"4","key":"3772_CR3","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1534\/genetics.105.044677","volume":"173","author":"C Greenman","year":"2006","unstructured":"Greenman C, Wooster R, Futreal PA, Stratton MR, Easton DF. Statistical analysis of pathogenicity of somatic mutations in cancer. 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