{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:20:35Z","timestamp":1772209235782,"version":"3.50.1"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17K07193"],"award-info":[{"award-number":["JP17K07193"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19H03795"],"award-info":[{"award-number":["JP19H03795"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17K11265"],"award-info":[{"award-number":["JP17K11265"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The National Cancer Center Research and Development Fund","award":["29-A-3"],"award-info":[{"award-number":["29-A-3"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ck0106319"],"award-info":[{"award-number":["JP19ck0106319"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Identification of the population frequencies of definitely pathogenic germline variants in two major hereditary breast and ovarian cancer syndrome (HBOC) genes,\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    , is essential to estimate the number of HBOC patients. In addition, the identification of moderately penetrant HBOC gene variants that contribute to increasing the risk of breast and ovarian cancers in a population is critical to establish personalized health care. A prospective cohort subjected to genome analysis can provide both sets of information. Computational scoring and prospective cohort studies may help to identify such likely pathogenic variants in the general population. We annotated the variants in the\n                    <jats:italic>BRCA1<\/jats:italic>\n                    and\n                    <jats:italic>BRCA2<\/jats:italic>\n                    genes from a dataset of 3,552 whole-genome sequences obtained from members of a prospective cohorts with genome data in the Tohoku Medical Megabank Project (TMM) with InterVar software. Computational impact scores (CADD_phred and Eigen_raw) and minor allele frequencies (MAFs) of pathogenic (P) and likely pathogenic (LP) variants in ClinVar were used for filtration criteria. Familial predispositions to cancers among the 35,000 TMM genome cohort participants were analyzed to verify the identified pathogenicity. Seven potentially pathogenic variants were newly identified. The sisters of carriers of these moderately deleterious variants and definite P and LP variants among members of the TMM prospective cohort showed a statistically significant preponderance for cancer onset, from the self-reported cancer history. Filtering by computational scoring and MAF is useful to identify potentially pathogenic variants in\n                    <jats:italic>BRCA<\/jats:italic>\n                    genes in the Japanese population. These results should help to follow up the carriers of variants of uncertain significance in the HBOC genes in the longitudinal prospective cohort study.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0236907","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T22:46:11Z","timestamp":1610405171000},"page":"e0236907","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes from a dataset of 3,552 Japanese whole genomes (3.5KJPNv2)"],"prefix":"10.1371","volume":"16","author":[{"given":"Hideki","family":"Tokunaga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Iida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Hozawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soichi","family":"Ogishima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoh","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shogo","family":"Shigeta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muneaki","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumi","family":"Yamaguchi-Kabata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8256-0735","authenticated-orcid":true,"given":"Shu","family":"Tadaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-7887","authenticated-orcid":true,"given":"Fumiki","family":"Katsuoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Kumada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Hamanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuo","family":"Fuse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kengo","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuo","family":"Yaegashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3887-6871","authenticated-orcid":true,"given":"Jun","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"issue":"9","key":"pone.0236907.ref001","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1056\/NEJMp1500523","article-title":"A new initiative on precision medicine","volume":"372","author":"FS Collins","year":"2015","journal-title":"The New England journal of medicine"},{"issue":"3","key":"pone.0236907.ref002","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s10689-016-9878-4","article-title":"Mullerian intra-abdominal carcinomatosis in hereditary breast ovarian cancer syndrome: implications for risk-reducing surgery","volume":"15","author":"MJ Casey","year":"2016","journal-title":"Fam Cancer"},{"key":"pone.0236907.ref003","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fonc.2016.00108","article-title":"Ovarian Cancer: The Fallopian Tube as the Site of Origin and Opportunities for Prevention","volume":"6","author":"SH George","year":"2016","journal-title":"Front Oncol"},{"issue":"9","key":"pone.0236907.ref004","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1093\/jjco\/hyy095","article-title":"Clinicopathologic features and BRCA mutations in primary fallopian tube cancer in Japanese women","volume":"48","author":"S Sakurada","year":"2018","journal-title":"Jpn J Clin Oncol"},{"issue":"6","key":"pone.0236907.ref005","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1136\/ijgc-2019-000384","article-title":"The first Japanese nationwide multicenter study of BRCA mutation testing in ovarian cancer: CHARacterizing the cross-sectionaL approach to Ovarian cancer geneTic TEsting of BRCA (CHARLOTTE)","volume":"29","author":"T Enomoto","year":"2019","journal-title":"Int J Gynecol Cancer"},{"issue":"2","key":"pone.0236907.ref006","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41416-018-0127-5","article-title":"BRCA1\/2 testing: therapeutic implications for breast cancer management","volume":"119","author":"NM Tung","year":"2018","journal-title":"Br J Cancer"},{"issue":"10","key":"pone.0236907.ref007","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.tcb.2019.07.008","article-title":"PARP Inhibitor Resistance: A Tug-of-War in BRCA-Mutated Cells","volume":"29","author":"SM Noordermeer","year":"2019","journal-title":"Trends Cell Biol"},{"issue":"20","key":"pone.0236907.ref008","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1200\/JCO.2016.71.6480","article-title":"Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer","volume":"35","author":"AW Kurian","year":"2017","journal-title":"J Clin Oncol"},{"issue":"10","key":"pone.0236907.ref009","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1111\/j.1349-7006.2008.00944.x","article-title":"Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast\/ovarian cancer","volume":"99","author":"K Sugano","year":"2008","journal-title":"Cancer Sci"},{"issue":"4","key":"pone.0236907.ref010","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s10038-017-0355-1","article-title":"Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan","volume":"63","author":"M Arai","year":"2018","journal-title":"J Hum Genet"},{"issue":"12","key":"pone.0236907.ref011","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1136\/jmedgenet-2018-105565","article-title":"Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort","volume":"55","author":"JS Lee","year":"2018","journal-title":"J Med Genet"},{"issue":"12","key":"pone.0236907.ref012","doi-asserted-by":"crossref","first-page":"e1007752","DOI":"10.1371\/journal.pgen.1007752","article-title":"BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2","volume":"14","author":"MS Cline","year":"2018","journal-title":"PLoS Genet"},{"issue":"1","key":"pone.0236907.ref013","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/humu.21628","article-title":"ENIGMA\u2014evidence-based network for the interpretation of germline mutant alleles: an international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes","volume":"33","author":"AB Spurdle","year":"2012","journal-title":"Hum Mutat"},{"issue":"1","key":"pone.0236907.ref014","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1038\/s41467-018-06581-8","article-title":"Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls","volume":"9","author":"Y Momozawa","year":"2018","journal-title":"Nat Commun"},{"issue":"9","key":"pone.0236907.ref015","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1093\/aje\/kwr453","article-title":"New models for large prospective studies: is there a better way?","volume":"175","author":"TA Manolio","year":"2012","journal-title":"Am J Epidemiol"},{"issue":"9","key":"pone.0236907.ref016","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2188\/jea.JE20150268","article-title":"The Tohoku Medical Megabank Project: Design and Mission","volume":"26","author":"S Kuriyama","year":"2016","journal-title":"J Epidemiol"},{"issue":"1","key":"pone.0236907.ref017","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1620\/tjem.248.45","article-title":"Biobank Establishment and Sample Management in the Tohoku Medical Megabank Project","volume":"248","author":"N Minegishi","year":"2019","journal-title":"Tohoku J Exp Med"},{"issue":"6","key":"pone.0236907.ref018","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/gtc.12588","article-title":"Omics research project on prospective cohort studies from the Tohoku Medical Megabank Project","volume":"23","author":"S Koshiba","year":"2018","journal-title":"Genes Cells"},{"issue":"2","key":"pone.0236907.ref019","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/jb\/mvy096","article-title":"Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare","volume":"165","author":"J Yasuda","year":"2019","journal-title":"J Biochem"},{"key":"pone.0236907.ref020","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41439-019-0059-5","article-title":"3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome","volume":"6","author":"S Tadaka","year":"2019","journal-title":"Hum Genome Var"},{"key":"pone.0236907.ref021","article-title":"Study profile of The Tohoku Medical Megabank Community-Based Cohort Study","author":"A Hozawa","year":"2020","journal-title":"J Epidemiol"},{"key":"pone.0236907.ref022","doi-asserted-by":"crossref","first-page":"8018","DOI":"10.1038\/ncomms9018","article-title":"Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals","volume":"6","author":"M Nagasaki","year":"2015","journal-title":"Nat Commun"},{"issue":"D1","key":"pone.0236907.ref023","doi-asserted-by":"crossref","first-page":"D551","DOI":"10.1093\/nar\/gkx978","article-title":"jMorp: Japanese Multi Omics Reference Panel","volume":"46","author":"S Tadaka","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pone.0236907.ref024","doi-asserted-by":"crossref","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses","volume":"54","author":"G Stelzer","year":"2016","journal-title":"Curr Protoc Bioinformatics"},{"issue":"21","key":"pone.0236907.ref025","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1093\/bioinformatics\/btr509","article-title":"A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data","volume":"27","author":"H Li","year":"2011","journal-title":"Bioinformatics"},{"issue":"16","key":"pone.0236907.ref026","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"2","key":"pone.0236907.ref027","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2017.01.004","article-title":"InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines","volume":"100","author":"Q Li","year":"2017","journal-title":"Am J Hum Genet"},{"issue":"16","key":"pone.0236907.ref028","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"K Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pone.0236907.ref029","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"issue":"Database issue","key":"pone.0236907.ref030","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":"3","key":"pone.0236907.ref031","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"M Kircher","year":"2014","journal-title":"Nat Genet"},{"issue":"5","key":"pone.0236907.ref032","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/bioinformatics\/btu703","article-title":"DANN: a deep learning approach for annotating the pathogenicity of genetic variants","volume":"31","author":"D Quang","year":"2015","journal-title":"Bioinformatics"},{"issue":"2","key":"pone.0236907.ref033","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/ng.3477","article-title":"A spectral approach integrating functional genomic annotations for coding and noncoding variants","volume":"48","author":"I Ionita-Laza","year":"2016","journal-title":"Nat Genet"},{"issue":"11","key":"pone.0236907.ref034","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/nmeth.3622","article-title":"TransVar: a multilevel variant annotator for precision genomics","volume":"12","author":"W Zhou","year":"2015","journal-title":"Nat Methods"},{"issue":"7616","key":"pone.0236907.ref035","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"M Lek","year":"2016","journal-title":"Nature"},{"issue":"269","key":"pone.0236907.ref036","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":"5","key":"pone.0236907.ref037","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"E Cerami","year":"2012","journal-title":"Cancer Discov"},{"issue":"1","key":"pone.0236907.ref038","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1038\/s41467-018-03274-0","article-title":"Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese","volume":"9","author":"Y Okada","year":"2018","journal-title":"Nat Commun"},{"issue":"2","key":"pone.0236907.ref039","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2018.03.039","article-title":"Pathogenic Germline Variants in 10,389 Adult Cancers","volume":"173","author":"KL Huang","year":"2018","journal-title":"Cell"},{"issue":"1","key":"pone.0236907.ref040","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12911-017-0494-5","article-title":"Security controls in an integrated Biobank to protect privacy in data sharing: rationale and study design","volume":"17","author":"T Takai-Igarashi","year":"2017","journal-title":"BMC Med Inform Decis Mak"},{"key":"pone.0236907.ref041","article-title":"Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): Rationale, Progress and Perspective","author":"S Kuriyama","year":"2019","journal-title":"Int J Epidemiol"},{"issue":"2","key":"pone.0236907.ref042","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s10038-017-0347-1","article-title":"Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals","volume":"63","author":"Y Yamaguchi-Kabata","year":"2018","journal-title":"J Hum Genet"},{"issue":"9","key":"pone.0236907.ref043","first-page":"696","article-title":"The BioBank Japan Project","volume":"5","author":"Y Nakamura","year":"2007","journal-title":"Clinical advances in hematology & oncology: H&O"},{"issue":"7","key":"pone.0236907.ref044","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1136\/jmg.2007.056895","article-title":"Screening BRCA1 and BRCA2 unclassified variants for splicing mutations using reverse transcription PCR on patient RNA and an ex vivo assay based on a splicing reporter minigene","volume":"45","author":"C Bonnet","year":"2008","journal-title":"J Med Genet"},{"issue":"9","key":"pone.0236907.ref045","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/jhg.2013.71","article-title":"Functional analysis of BRCA1 missense variants of uncertain significance in Japanese breast cancer families","volume":"58","author":"S Kawaku","year":"2013","journal-title":"J Hum Genet"},{"issue":"11","key":"pone.0236907.ref046","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1158\/0008-5472.CAN-16-2568","article-title":"BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer","volume":"77","author":"H Shimelis","year":"2017","journal-title":"Cancer Res"},{"issue":"6","key":"pone.0236907.ref047","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1182\/blood-2017-02-769869","article-title":"Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly","volume":"130","author":"F Zink","year":"2017","journal-title":"Blood"},{"issue":"D1","key":"pone.0236907.ref048","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"P Rentzsch","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"pone.0236907.ref049","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00439-019-01975-0","article-title":"Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data","volume":"138","author":"KY He","year":"2019","journal-title":"Hum Genet"},{"issue":"5","key":"pone.0236907.ref050","doi-asserted-by":"crossref","first-page":"e271","DOI":"10.1212\/NXG.0000000000000271","article-title":"Plasticity-related gene 3 (LPPR1) and age at diagnosis of Parkinson disease","volume":"4","author":"ZD Wallen","year":"2018","journal-title":"Neurol Genet"},{"issue":"7793","key":"pone.0236907.ref051","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41586-020-1969-6","article-title":"Pan-cancer analysis of whole genomes","volume":"578","author":"Consortium ITP-CAoWG","year":"2020","journal-title":"Nature"},{"issue":"7726","key":"pone.0236907.ref052","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41586-018-0461-z","article-title":"Accurate classification of BRCA1 variants with saturation genome editing","volume":"562","author":"GM Findlay","year":"2018","journal-title":"Nature"},{"issue":"7359","key":"pone.0236907.ref053","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nature10275","article-title":"A continuum model for tumour suppression","volume":"476","author":"AH Berger","year":"2011","journal-title":"Nature"},{"issue":"7","key":"pone.0236907.ref054","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1111\/j.1349-7006.2010.01590.x","article-title":"Genome-wide germline analyses on cancer susceptibility and GeMDBJ database: Gastric cancer as an example","volume":"101","author":"T Yoshida","year":"2010","journal-title":"Cancer Sci"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0236907","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T22:48:22Z","timestamp":1610405302000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0236907"}},"subtitle":[],"editor":[{"given":"Yonglan","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0236907","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.07.17.208454","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]}}}