{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:08:59Z","timestamp":1771463339696,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"W1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,3]]},"DOI":"10.1093\/nar\/gkx367","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T07:37:59Z","timestamp":1493019479000},"page":"W514-W522","source":"Crossref","is-referenced-by-count":76,"title":["Exploring background mutational processes to decipher cancer genetic heterogeneity"],"prefix":"10.1093","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-7146","authenticated-orcid":false,"given":"Alexander","family":"Goncearenco","sequence":"first","affiliation":[]},{"given":"Stephanie L.","family":"Rager","sequence":"additional","affiliation":[]},{"given":"Minghui","family":"Li","sequence":"additional","affiliation":[]},{"given":"Qing-Xiang","family":"Sang","sequence":"additional","affiliation":[]},{"given":"Igor B.","family":"Rogozin","sequence":"additional","affiliation":[]},{"given":"Anna R.","family":"Panchenko","sequence":"additional","affiliation":[]}],"member":"286","published-online":{"date-parts":[[2017,5,4]]},"reference":[{"key":"key\n\t\t\t\t20180201083710_B1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature12213","article-title":"Mutational heterogeneity in cancer and the search for new cancer-associated genes","volume":"499","author":"Lawrence","year":"2013","journal-title":"Nature"},{"key":"key\n\t\t\t\t20180201083710_B2","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.1158\/0008-5472.CAN-12-2217","article-title":"Intratumor heterogeneity: evolution through space and time","volume":"72","author":"Swanton","year":"2012","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20180201083710_B3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nm.3984","article-title":"Pan-cancer analysis of the extent and consequences of intratumor heterogeneity","volume":"22","author":"Andor","year":"2016","journal-title":"Nat. Med."},{"key":"key\n\t\t\t\t20180201083710_B4","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/ng.3292","article-title":"Genome-wide patterns and properties of de novo mutations in humans","volume":"47","author":"Francioli","year":"2015","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20180201083710_B5","doi-asserted-by":"crossref","first-page":"e1002419","DOI":"10.1371\/journal.pbio.1002419","article-title":"Low genetic quality alters key dimensions of the mutational spectrum","volume":"14","author":"Sharp","year":"2016","journal-title":"PLoS Biol."},{"key":"key\n\t\t\t\t20180201083710_B6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0027-5107(03)00013-7","article-title":"On the origin of G\u2192T transversions in lung cancer","volume":"526","author":"Pfeifer","year":"2003","journal-title":"Mutat. Res."},{"key":"key\n\t\t\t\t20180201083710_B7","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/ng.3315","article-title":"Spatial genomic heterogeneity within localized, multifocal prostate cancer","volume":"47","author":"Boutros","year":"2015","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20180201083710_B8","doi-asserted-by":"crossref","first-page":"8683","DOI":"10.1038\/ncomms9683","article-title":"A mutational signature in gastric cancer suggests therapeutic strategies","volume":"6","author":"Alexandrov","year":"2015","journal-title":"Nat. Commun."},{"key":"key\n\t\t\t\t20180201083710_B9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature12634","article-title":"Mutational landscape and significance across 12 major cancer types","volume":"502","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"key\n\t\t\t\t20180201083710_B10","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.cell.2012.04.024","article-title":"Mutational processes molding the genomes of 21 breast cancers","volume":"149","author":"Nik-Zainal","year":"2012","journal-title":"Cell"},{"key":"key\n\t\t\t\t20180201083710_B11","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/ng.3252","article-title":"Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets","volume":"47","author":"Schulze","year":"2015","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20180201083710_B12","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/php.12377","article-title":"UV signature mutations","volume":"91","author":"Brash","year":"2015","journal-title":"Photochem. Photobiol."},{"key":"key\n\t\t\t\t20180201083710_B13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13073-015-0161-3","article-title":"Mutation signatures implicate aristolochic acid in bladder cancer development","volume":"7","author":"Poon","year":"2015","journal-title":"Genome Med."},{"key":"key\n\t\t\t\t20180201083710_B14","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1093\/carcin\/bgv031","article-title":"Causes of genome instability: the effect of low dose chemical exposures in modern society","volume":"36","author":"Langie","year":"2015","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20180201083710_B15","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/ng.2702","article-title":"An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers","volume":"45","author":"Roberts","year":"2013","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20180201083710_B16","doi-asserted-by":"crossref","first-page":"5691","DOI":"10.1158\/0008-5472.CAN-06-4314","article-title":"Background mutation frequency in microsatellite-unstable colorectal cancer","volume":"67","author":"Sammalkorpi","year":"2007","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20180201083710_B17","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1093\/molbev\/msv055","article-title":"Asymmetric context-dependent mutation patterns revealed through mutation-accumulation experiments","volume":"32","author":"Sung","year":"2015","journal-title":"Mol. Biol. Evol."},{"key":"key\n\t\t\t\t20180201083710_B18","first-page":"10083","article-title":"The current state of eukaryotic DNA base damage and repair","volume":"43","author":"Bauer","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20180201083710_B19","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1093\/molbev\/msh039","article-title":"Phylogenetic estimation of context-dependent substitution rates by maximum likelihood","volume":"21","author":"Siepel","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"key\n\t\t\t\t20180201083710_B20","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00439-009-0657-2","article-title":"Mutational spectra of human cancer","volume":"125","author":"Pfeifer","year":"2009","journal-title":"Hum. Genet."},{"key":"key\n\t\t\t\t20180201083710_B21","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"key\n\t\t\t\t20180201083710_B22","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nrg3729","article-title":"Mechanisms underlying mutational signatures in human cancers","volume":"15","author":"Helleday","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"key\n\t\t\t\t20180201083710_B23","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1093\/bib\/4.3.210","article-title":"Computational analysis of mutation spectra","volume":"4","author":"Rogozin","year":"2003","journal-title":"Brief Bioinform."},{"key":"key\n\t\t\t\t20180201083710_B24","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/carcin\/bgw055","article-title":"Understanding mutagenesis through delineation of mutational signatures in human cancer","volume":"37","author":"Petljak","year":"2016","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20180201083710_B25","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/onc.2016.192","article-title":"Base changes in tumour DNA have the power to reveal the causes and evolution of cancer","volume":"36","author":"Hollstein","year":"2016","journal-title":"Oncogene"},{"key":"key\n\t\t\t\t20180201083710_B26","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"key\n\t\t\t\t20180201083710_B27","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s12859-016-1011-z","article-title":"MutSpec: a Galaxy toolbox for streamlined analyses of somatic mutation spectra in human and mouse cancer genomes","volume":"17","author":"Ardin","year":"2016","journal-title":"BMC Bioinformatics"},{"key":"key\n\t\t\t\t20180201083710_B28","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1093\/bioinformatics\/btv408","article-title":"SomaticSignatures: inferring mutational signatures from single-nucleotide variants","volume":"31","author":"Gehring","year":"2015","journal-title":"Bioinformatics"},{"key":"key\n\t\t\t\t20180201083710_B29","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1158\/0008-5472.CAN-14-3812","article-title":"Balancing protein stability and activity in cancer: a new approach for identifying driver mutations affecting CBL ubiquitin ligase activation","volume":"76","author":"Li","year":"2016","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20180201083710_B30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/978-1-4939-6747-6_17","article-title":"Annotating mutational effects on proteins and protein interactions: designing novel and revisiting existing protocols","volume":"1550","author":"Li","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"key\n\t\t\t\t20180201083710_B31","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1073\/pnas.1213968110","article-title":"Impact of deleterious passenger mutations on cancer progression","volume":"110","author":"McFarland","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"key\n\t\t\t\t20180201083710_B32","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1073\/pnas.0912629107","article-title":"Rate, molecular spectrum, and consequences of human mutation","volume":"107","author":"Lynch","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"key\n\t\t\t\t20180201083710_B33","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nbt.3391","article-title":"Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity","volume":"34","author":"Chang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"key\n\t\t\t\t20180201083710_B34","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1158\/0008-5472.CAN-09-1133","article-title":"Cancer-specific high-throughput annotation of somatic mutations: computational prediction of driver missense mutations","volume":"69","author":"Carter","year":"2009","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20180201083710_B35","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nmeth.2562","article-title":"Computational approaches to identify functional genetic variants in cancer genomes","volume":"10","author":"Gonzalez-Perez","year":"2013","journal-title":"Nat. Methods"},{"key":"key\n\t\t\t\t20180201083710_B36","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","article-title":"The Cancer Genome Atlas Pan-cancer analysis project","volume":"45","author":"Cancer Genome Atlas Research, N.","year":"2013","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20180201083710_B37","doi-asserted-by":"crossref","first-page":"D805","DOI":"10.1093\/nar\/gku1075","article-title":"COSMIC: exploring the world's knowledge of somatic mutations in human cancer","volume":"43","author":"Forbes","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20180201083710_B38","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1093\/nar\/gkw086","article-title":"The landscape of somatic mutations in protein coding genes in apparently benign human tissues carries signatures of relaxed purifying selection","volume":"44","author":"Yadav","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20180201083710_B39","doi-asserted-by":"crossref","first-page":"D7","DOI":"10.1093\/nar\/gkt1146","article-title":"Database resources of the National Center for Biotechnology Information","volume":"42","author":"Coordinators","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20180201083710_B40","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.celrep.2012.12.008","article-title":"Deciphering signatures of mutational processes operative in human cancer","volume":"3","author":"Alexandrov","year":"2013","journal-title":"Cell Rep."},{"key":"key\n\t\t\t\t20180201083710_B41","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13059-016-0893-4","article-title":"DeconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution","volume":"17","author":"Rosenthal","year":"2016","journal-title":"Genome Biol."},{"key":"key\n\t\t\t\t20180201083710_B42","doi-asserted-by":"crossref","first-page":"4164","DOI":"10.1073\/pnas.0308531101","article-title":"Metagenes and molecular pattern discovery using matrix factorization","volume":"101","author":"Brunet","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"key\n\t\t\t\t20180201083710_B43","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1109\/TPAMI.2006.60","article-title":"Nonsmooth nonnegative matrix factorization (nsNMF)","volume":"28","author":"Pascual-Montano","year":"2006","journal-title":"IEEE Trans Pattern Anal. Mach. Intell."},{"key":"key\n\t\t\t\t20180201083710_B44","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.1260825","article-title":"Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions","volume":"347","author":"Tomasetti","year":"2015","journal-title":"Science"},{"key":"key\n\t\t\t\t20180201083710_B45","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1383-5742(03)00032-2","article-title":"Theoretical analysis of mutation hotspots and their DNA sequence context specificity","volume":"544","author":"Rogozin","year":"2003","journal-title":"Mutat. Res."},{"key":"key\n\t\t\t\t20180201083710_B46","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/molbev\/msl156","article-title":"Methylation-dependent transition rates are dependent on local sequence lengths and genomic regions","volume":"24","author":"Zhao","year":"2007","journal-title":"Mol. Biol. Evol."},{"key":"key\n\t\t\t\t20180201083710_B47","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/humu.20495","article-title":"Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database","volume":"28","author":"Petitjean","year":"2007","journal-title":"Hum. Mutat."},{"key":"key\n\t\t\t\t20180201083710_B48","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1038\/sj.onc.1210302","article-title":"TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes","volume":"26","author":"Petitjean","year":"2007","journal-title":"Oncogene"},{"key":"key\n\t\t\t\t20180201083710_B49","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.gde.2013.11.014","article-title":"Mutational signatures: the patterns of somatic mutations hidden in cancer genomes","volume":"24","author":"Alexandrov","year":"2014","journal-title":"Curr. Opin. Genet. Dev."},{"key":"key\n\t\t\t\t20180201083710_B50","doi-asserted-by":"crossref","first-page":"38133","DOI":"10.1038\/srep38133","article-title":"Activation induced deaminase mutational signature overlaps with CpG methylation sites in follicular lymphoma and other cancers","volume":"6","author":"Rogozin","year":"2016","journal-title":"Sci. Rep."},{"key":"key\n\t\t\t\t20180201083710_B51","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1158\/2159-8290.CD-15-0439","article-title":"Evolutionary determinants of cancer","volume":"5","author":"Greaves","year":"2015","journal-title":"Cancer Discov."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/45\/W1\/W514\/23741053\/gkx367.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T07:24:45Z","timestamp":1692775485000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/45\/W1\/W514\/3796332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,4]]},"references-count":51,"journal-issue":{"issue":"W1","published-online":{"date-parts":[[2017,5,4]]},"published-print":{"date-parts":[[2017,7,3]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkx367","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,7,3]]},"published":{"date-parts":[[2017,5,4]]}}}