{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:09:23Z","timestamp":1772172563109,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1006981","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T00:00:00Z","timestamp":1556496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000092","name":"U.S. National Library of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31701136"],"award-info":[{"award-number":["31701136"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20170335"],"award-info":[{"award-number":["BK20170335"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1006981","type":"journal-article","created":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T13:36:46Z","timestamp":1556545006000},"page":"e1006981","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":85,"title":["Finding driver mutations in cancer: Elucidating the role of background mutational processes"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1493-208X","authenticated-orcid":true,"given":"Anna-Leigh","family":"Brown","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2056-1249","authenticated-orcid":true,"given":"Minghui","family":"Li","sequence":"additional","affiliation":[]},{"given":"Alexander","family":"Goncearenco","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-1131","authenticated-orcid":true,"given":"Anna R.","family":"Panchenko","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2019,4,29]]},"reference":[{"issue":"3","key":"ref1","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":"M. Lynch","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7132","key":"ref2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nature05610","article-title":"Patterns of somatic mutation in human cancer genomes","volume":"446","author":"C Greenman","year":"2007","journal-title":"Nature"},{"issue":"13","key":"ref3","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1158\/0008-5472.CAN-12-1052","article-title":"The continuum model of selection in human tumors: general paradigm or niche product?","volume":"72","author":"S Leedham","year":"2012","journal-title":"Cancer research"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.sbi.2015.01.004","article-title":"&apos;Latent drivers&apos; expand the cancer mutational landscape","volume":"32","author":"R Nussinov","year":"2015","journal-title":"Curr Opin Struct Biol"},{"issue":"2","key":"ref5","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrclinonc.2017.166","article-title":"Tumour heterogeneity and resistance to cancer therapies","volume":"15","author":"I Dagogo-Jack","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"issue":"8","key":"ref6","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1186\/s13059-014-0453-8","article-title":"Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine","volume":"15","author":"C Hiley","year":"2014","journal-title":"Genome Biol"},{"issue":"5","key":"ref7","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":"S Nik-Zainal","year":"2012","journal-title":"Cell"},{"issue":"7463","key":"ref8","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"LB Alexandrov","year":"2013","journal-title":"Nature"},{"key":"ref9","article-title":"Mutational signatures and mutable motifs in cancer genomes","author":"IB Rogozin","year":"2017","journal-title":"Briefings in bioinformatics"},{"issue":"7","key":"ref10","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1016\/j.cell.2012.11.019","article-title":"Whole-genome sequencing in autism identifies hot spots for de novo germline mutation","volume":"151","author":"JJ Michaelson","year":"2012","journal-title":"Cell"},{"issue":"11","key":"ref11","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/nrg3098","article-title":"Variation in the mutation rate across mammalian genomes","volume":"12","author":"A Hodgkinson","year":"2011","journal-title":"Nature reviews Genetics"},{"issue":"11","key":"ref12","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nrg.2016.104","article-title":"Genetic drift, selection and the evolution of the mutation rate","volume":"17","author":"M Lynch","year":"2016","journal-title":"Nature reviews Genetics"},{"issue":"6024","key":"ref13","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1126\/science.1204040","article-title":"Exploring the genomes of cancer cells: progress and promise","volume":"331","author":"MR Stratton","year":"2011","journal-title":"Science"},{"issue":"7539","key":"ref14","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nature14221","article-title":"Cell-of-origin chromatin organization shapes the mutational landscape of cancer","volume":"518","author":"P Polak","year":"2015","journal-title":"Nature"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0167-4781(92)90134-L","article-title":"Somatic hypermutagenesis in immunoglobulin genes. II. Influence of neighbouring base sequences on mutagenesis","volume":"1171","author":"IB Rogozin","year":"1992","journal-title":"Biochimica et biophysica acta"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1534\/genetics.117.1114","article-title":"Contrasting Determinants of Mutation Rates in Germline and Soma","volume":"207","author":"C Chen","year":"2017","journal-title":"Genetics"},{"issue":"21","key":"ref17","doi-asserted-by":"crossref","first-page":"e169","DOI":"10.1093\/nar\/gks743","article-title":"Functional impact bias reveals cancer drivers","volume":"40","author":"A Gonzalez-Perez","year":"2012","journal-title":"Nucleic acids research"},{"issue":"5","key":"ref18","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.cell.2017.09.042","article-title":"Universal Patterns of Selection in Cancer and Somatic Tissues","volume":"171","author":"I Martincorena","year":"2017","journal-title":"Cell"},{"issue":"2","key":"ref19","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/ng.3471","article-title":"Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations","volume":"48","author":"CL Araya","year":"2016","journal-title":"Nature genetics"},{"issue":"4","key":"ref20","doi-asserted-by":"crossref","first-page":"e1005428","DOI":"10.1371\/journal.pcbi.1005428","article-title":"Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples.","volume":"13","author":"TA Peterson","year":"2017","journal-title":"PLoS computational biology"},{"issue":"2","key":"ref21","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":"MT Chang","year":"2016","journal-title":"Nature biotechnology"},{"issue":"8","key":"ref22","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/nmeth.4364","article-title":"Comparison of algorithms for the detection of cancer drivers at subgene resolution","volume":"14","author":"E Porta-Pardo","year":"2017","journal-title":"Nature methods"},{"issue":"15","key":"ref23","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1093\/bioinformatics\/btr357","article-title":"CHASM and SNVBox: toolkit for detecting biologically important single nucleotide mutations in cancer","volume":"27","author":"WC Wong","year":"2011","journal-title":"Bioinformatics"},{"issue":"3","key":"ref24","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":"M Li","year":"2016","journal-title":"Cancer research"},{"issue":"5","key":"ref25","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.cell.2017.09.048","article-title":"Comprehensive Analysis of Hypermutation in Human Cancer","volume":"171","author":"BB Campbell","year":"2017","journal-title":"Cell"},{"issue":"2","key":"ref26","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.cell.2018.02.060","article-title":"Comprehensive Characterization of Cancer Driver Genes and Mutations","volume":"173","author":"MH Bailey","year":"2018","journal-title":"Cell"},{"issue":"3","key":"ref27","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/humu.22493","article-title":"Activating mutations cluster in the &quot;molecular brake&quot; regions of protein kinases and do not associate with conserved or catalytic residues","volume":"35","author":"MA Molina-Vila","year":"2014","journal-title":"Hum Mutat"},{"issue":"7","key":"ref28","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1002\/humu.23236","article-title":"Large differences in proportions of harmful and benign amino acid substitutions between proteins and diseases","volume":"38","author":"GCP Schaafsma","year":"2017","journal-title":"Hum Mutat"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1476-4598-10-54","article-title":"The structural impact of cancer-associated missense mutations in oncogenes and tumor suppressors","volume":"10","author":"H Stehr","year":"2011","journal-title":"Mol Cancer"},{"issue":"2","key":"ref30","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1158\/2159-8290.CD-17-0321","article-title":"Accelerating Discovery of Functional Mutant Alleles in Cancer.","volume":"8","author":"MT Chang","year":"2018","journal-title":"Cancer Discov"},{"issue":"16","key":"ref31","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":"H Carter","year":"2009","journal-title":"Cancer research"},{"key":"ref32","article-title":"CHASMplus reveals the scope of somatic missense mutations driving human cancers","author":"C Tokheim","year":"2019","journal-title":"CHASMplus reveals the scope of somatic missense mutations driving human cancers"},{"issue":"1","key":"ref33","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/humu.22911","article-title":"Assessing the Pathogenicity of Insertion and Deletion Variants with the Variant Effect Scoring Tool (VEST-Indel).","volume":"37","author":"C Douville","year":"2016","journal-title":"Hum Mutat"},{"issue":"4","key":"ref34","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ajhg.2016.08.016","article-title":"REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants","volume":"99","author":"NM Ioannidis","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"10","key":"ref35","doi-asserted-by":"crossref","first-page":"e77945","DOI":"10.1371\/journal.pone.0077945","article-title":"CanDrA: cancer-specific driver missense mutation annotation with optimized features","volume":"8","author":"Y Mao","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"ref36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/humu.22225","article-title":"Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models","volume":"34","author":"HA Shihab","year":"2013","journal-title":"Hum Mutat"},{"issue":"7457","key":"ref37","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":"MS Lawrence","year":"2013","journal-title":"Nature"},{"issue":"W1","key":"ref38","doi-asserted-by":"crossref","first-page":"W514","DOI":"10.1093\/nar\/gkx367","article-title":"Exploring background mutational processes to decipher cancer genetic heterogeneity","volume":"45","author":"A Goncearenco","year":"2017","journal-title":"Nucleic acids research"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/1471-2164-9-292","article-title":"Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome","volume":"9","author":"IP Gorlov","year":"2008","journal-title":"BMC Genomics"},{"issue":"6","key":"ref40","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.cell.2014.01.051","article-title":"Synonymous mutations frequently act as driver mutations in human cancers","volume":"156","author":"F Supek","year":"2014","journal-title":"Cell"},{"issue":"10","key":"ref41","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/nmeth.4000","article-title":"DoCM: a database of curated mutations in cancer","volume":"13","author":"BJ Ainscough","year":"2016","journal-title":"Nat Methods"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","article-title":"ClinVar: public archive of relationships among sequence variation and human phenotype","volume":"42","author":"MJ Landrum","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"ref43","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/humu.10081","article-title":"The IARC TP53 database: new online mutation analysis and recommendations to users","volume":"19","author":"M Olivier","year":"2002","journal-title":"Hum Mutat"},{"issue":"10","key":"ref44","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1186\/s13059-014-0484-1","article-title":"Benchmarking mutation effect prediction algorithms using functionally validated cancer-related missense mutations","volume":"15","author":"LG Martelotto","year":"2014","journal-title":"Genome Biol"},{"issue":"2","key":"ref45","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1534\/genetics.115.175802","article-title":"Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.","volume":"200","author":"LM Starita","year":"2015","journal-title":"Genetics"},{"issue":"1","key":"ref46","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40246-017-0104-8","article-title":"Variant effect prediction tools assessed using independent, functional assay-based datasets: implications for discovery and diagnostics","volume":"11","author":"K Mahmood","year":"2017","journal-title":"Hum Genomics"},{"issue":"3","key":"ref47","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccell.2018.01.021","article-title":"Systematic Functional Annotation of Somatic Mutations in Cancer","volume":"33","author":"PK Ng","year":"2018","journal-title":"Cancer Cell"},{"issue":"D1","key":"ref48","doi-asserted-by":"crossref","first-page":"D777","DOI":"10.1093\/nar\/gkw1121","article-title":"COSMIC: somatic cancer genetics at high-resolution","volume":"45","author":"SA Forbes","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"269","key":"ref49","first-page":"pl1","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"J Gao","year":"2013","journal-title":"Sci Signal"},{"issue":"7391","key":"ref50","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature11003","article-title":"The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity","volume":"483","author":"J Barretina","year":"2012","journal-title":"Nature"},{"issue":"1","key":"ref51","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: the NCBI database of genetic variation","volume":"29","author":"ST Sherry","year":"2001","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"ref52","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1109\/TNB.2013.2263391","article-title":"Adjusting for background mutation frequency biases improves the identification of cancer driver genes","volume":"12","author":"P Evans","year":"2013","journal-title":"IEEE Trans Nanobioscience"},{"issue":"3","key":"ref53","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/humu.22932","article-title":"dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Nonsynonymous and Splice-Site SNVs","volume":"37","author":"X Liu","year":"2016","journal-title":"Hum Mutat"},{"issue":"5","key":"ref54","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/bioinformatics\/btt017","article-title":"CRAVAT: cancer-related analysis of variants toolkit","volume":"29","author":"C Douville","year":"2013","journal-title":"Bioinformatics"},{"issue":"2","key":"ref55","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/0005-2795(75)90109-9","article-title":"Comparison of the predicted and observed secondary structure of T4 phage lysozyme","volume":"405","author":"B. Matthews","year":"1975","journal-title":"Biochimica et biophysica acta"},{"issue":"6217","key":"ref56","first-page":"78","article-title":"Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions","volume":"347","author":"C. Tomasetti","year":"2015"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1006981","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006981","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T03:27:07Z","timestamp":1588994827000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006981"}},"subtitle":[],"editor":[{"given":"Ruth","family":"Nussinov","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2019,4,29]]},"references-count":56,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1006981","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/354506","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,29]]}}}