{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T04:54:25Z","timestamp":1776574465567,"version":"3.51.2"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Israel Academy of Sciences","award":["# 2479\/20"],"award-info":[{"award-number":["# 2479\/20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Correctly identifying the true driver mutations in a patient\u2019s tumor is a major challenge in precision oncology. Most efforts address frequent mutations, leaving medium- and low-frequency variants mostly unaddressed. For TP53, this identification is crucial for both somatic and germline mutations, with the latter associated with the Li-Fraumeni syndrome (LFS), a multiorgan cancer predisposition. We present TP53_PROF (prediction of functionality), a gene specific machine learning model to predict the functional consequences of every possible missense mutation in TP53, integrating human cell- and yeast-based functional assays scores along with computational scores. Variants were labeled for the training set using well-defined criteria of prevalence in four cancer genomics databases. The model\u2019s predictions provided accuracy of 96.5%. They were validated experimentally, and were compared to population data, LFS datasets, ClinVar annotations and to TCGA survival data. Very high accuracy was shown through all methods of validation. TP53_PROF allows accurate classification of TP53 missense mutations applicable for clinical practice. Our gene specific approach integrated machine learning, highly reliable features and biological knowledge, to create an unprecedented, thoroughly validated and clinically oriented classification model. This approach currently addresses TP53 mutations and will be applied in the future to other important cancer genes.<\/jats:p>","DOI":"10.1093\/bib\/bbab524","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T20:14:15Z","timestamp":1637007255000},"source":"Crossref","is-referenced-by-count":21,"title":["TP53_PROF: a machine learning model to predict impact of missense mutations in <i>TP53<\/i>"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8857-6124","authenticated-orcid":false,"given":"Gil","family":"Ben-Cohen","sequence":"first","affiliation":[{"name":"Gaffin Center for Neuro-Oncology, Sharett Institute for Oncology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel"},{"name":"The Wohl Institute for Translational Medicine, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora","family":"Doffe","sequence":"additional","affiliation":[{"name":"INSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris-Sud, Universit\u00e9 Paris-Saclay, 94805 Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Devir","sequence":"additional","affiliation":[{"name":"Gaffin Center for Neuro-Oncology, Sharett Institute for Oncology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel"},{"name":"The Wohl Institute for Translational Medicine, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Leroy","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UPMC Univ Paris 06, F- 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Soussi","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UPMC Univ Paris 06, F- 75005 Paris, France"},{"name":"INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France"},{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shai","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Gaffin Center for Neuro-Oncology, Sharett Institute for Oncology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel"},{"name":"The Wohl Institute for Translational Medicine, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"issue":"10","key":"2022031506230728800_ref1","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/ng.2762","article-title":"Emerging landscape of oncogenic signatures across human cancers","volume":"45","author":"Ciriello","year":"2013","journal-title":"Nat Genet"},{"key":"2022031506230728800_ref2","doi-asserted-by":"crossref","first-page":"10086","DOI":"10.1038\/ncomms10086","article-title":"Patterns and functional implications of rare germline variants across 12 cancer types","volume":"6","author":"Lu","year":"2015","journal-title":"Nat Commun"},{"issue":"6","key":"2022031506230728800_ref3","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nm.3559","article-title":"Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine","volume":"20","author":"Van Allen","year":"2014","journal-title":"Nat Med"},{"issue":"8","key":"2022031506230728800_ref4","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1056\/NEJMoa1112302","article-title":"Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib","volume":"366","author":"Sosman","year":"2012","journal-title":"N Engl J Med"},{"issue":"10","key":"2022031506230728800_ref5","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMe0905763","article-title":"Personalized medicine and inhibition of EGFR signaling in lung cancer","volume":"361","author":"Gazdar","year":"2009","journal-title":"N Engl J Med"},{"issue":"32","key":"2022031506230728800_ref6","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1200\/JCO.2015.61.5997","article-title":"Impact of precision medicine in diverse cancers: a meta-analysis of phase II clinical trials","volume":"33","author":"Schwaederle","year":"2015","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"issue":"6","key":"2022031506230728800_ref7","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm.4333","article-title":"Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients","volume":"23","author":"Zehir","year":"2017","journal-title":"Nat Med"},{"issue":"3","key":"2022031506230728800_ref8","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.ccell.2015.02.007","article-title":"In silico prescription of anticancer drugs to cohorts of 28 tumor types reveals targeting opportunities","volume":"27","author":"Rubio-Perez","year":"2015","journal-title":"Cancer Cell"},{"issue":"2","key":"2022031506230728800_ref9","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":"Chang","year":"2018","journal-title":"Cancer Discov"},{"issue":"7","key":"2022031506230728800_ref10","first-page":"787","article-title":"Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study","volume":"19","author":"Ghazani","year":"2017","journal-title":"Genet Med Off J Am College Med Genet"},{"key":"2022031506230728800_ref11","article-title":"OncoKB: a precision oncology knowledge base","volume":"2017","author":"Chakravarty","year":"2017","journal-title":"JCO Precis Oncol"},{"issue":"1","key":"2022031506230728800_ref12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13073-018-0531-8","article-title":"Cancer genome interpreter annotates the biological and clinical relevance of tumor alterations","volume":"10","author":"Tamborero","year":"2018","journal-title":"Genome Med"},{"issue":"11","key":"2022031506230728800_ref13","doi-asserted-by":"crossref","DOI":"10.1038\/s41436-021-01265-z","article-title":"Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes","volume":"23","author":"Cubuk","year":"2021","journal-title":"Genet Med"},{"issue":"16","key":"2022031506230728800_ref14","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"},{"issue":"1","key":"2022031506230728800_ref15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13059-020-01954-z","article-title":"Comprehensive assessment of computational algorithms in predicting cancer driver mutations","volume":"21","author":"Chen","year":"2020","journal-title":"Genome Biol"},{"issue":"5","key":"2022031506230728800_ref16","first-page":"405","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":"Richards","year":"2015","journal-title":"Genet Med Off J Am College Med Genet"},{"issue":"5","key":"2022031506230728800_ref17","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1016\/j.celrep.2019.07.001","article-title":"Integrated analysis of TP53 gene and pathway alterations in the Cancer Genome Atlas","volume":"28","author":"Donehower","year":"2019","journal-title":"Cell Rep"},{"issue":"4","key":"2022031506230728800_ref18","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a026187","article-title":"Inherited TP53 mutations and the Li-Fraumeni syndrome","volume":"7","author":"Guha","year":"2017","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"4","key":"2022031506230728800_ref19","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s10689-019-00140-w","article-title":"TP53 variants of uncertain significance: increasing challenges in variant interpretation and genetic counseling","volume":"18","author":"Bittar","year":"2019","journal-title":"Fam Cancer"},{"issue":"8","key":"2022031506230728800_ref20","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1002\/humu.23553","article-title":"Improved, ACMG-compliant, in silico prediction of pathogenicity for missense substitutions encoded by TP53 variants","volume":"39","author":"Fortuno","year":"2018","journal-title":"Hum Mutat"},{"key":"2022031506230728800_ref21","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1158\/0008-5472.CAN-16-2179","article-title":"Recommended guidelines for validation, quality control, and reporting of TP53 variants in clinical practice","volume":"6","author":"Leroy","year":"2017","journal-title":"Cancer Res"},{"issue":"14","key":"2022031506230728800_ref22","doi-asserted-by":"crossref","first-page":"8424","DOI":"10.1073\/pnas.1431692100","article-title":"Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis","volume":"100","author":"Kato","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"2022031506230728800_ref23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/humu.20269","article-title":"The UMD TP53 database and website: update and revisions","volume":"27","author":"Hamroun","year":"2006","journal-title":"Hum Mutat"},{"issue":"6","key":"2022031506230728800_ref24","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.cell.2017.08.028","article-title":"Putting p53 in context","volume":"170","author":"Kastenhuber","year":"2017","journal-title":"Cell"},{"issue":"10","key":"2022031506230728800_ref25","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/s41588-018-0204-y","article-title":"Mutational processes shape the landscape of TP53 mutations in human cancer","volume":"50","author":"Giacomelli","year":"2018","journal-title":"Nat Genet"},{"issue":"5","key":"2022031506230728800_ref26","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.molcel.2018.08.013","article-title":"A systematic p53 mutation library links differential functional impact to cancer mutation pattern and evolutionary conservation","volume":"71","author":"Kotler","year":"2018","journal-title":"Mol Cell"},{"issue":"11","key":"2022031506230728800_ref27","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1016\/j.celrep.2019.08.061","article-title":"Integrated analysis of TP53 gene and pathway alterations in the cancer genome atlas","volume":"28","author":"Donehower","year":"2019","journal-title":"Cell Rep"},{"issue":"Database issue","key":"2022031506230728800_ref28","doi-asserted-by":"crossref","first-page":"D962","DOI":"10.1093\/nar\/gks1033","article-title":"The TP53 website: an integrative resource centre for the TP53 mutation database and TP53 mutant analysis","volume":"41","author":"Leroy","year":"2013","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"2022031506230728800_ref29","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.22981","article-title":"HGVS recommendations for the description of sequence variants: 2016 update","volume":"37","author":"Dunnen","year":"2016","journal-title":"Hum Mutat"},{"issue":"7616","key":"2022031506230728800_ref30","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":"Lek","year":"2016","journal-title":"Nature"},{"issue":"8","key":"2022031506230728800_ref31","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1002\/humu.21517","article-title":"dbNSFP: a lightweight database of human nonsynonymous SNPs and their functional predictions","volume":"32","author":"Liu","year":"2011","journal-title":"Hum Mutat"},{"issue":"1","key":"2022031506230728800_ref32","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/humu.20114","article-title":"Reassessment of the TP53 mutation database in human disease by data mining with a library of TP53 missense mutations","volume":"25","author":"Soussi","year":"2005","journal-title":"Hum Mutat"},{"issue":"1","key":"2022031506230728800_ref33","doi-asserted-by":"crossref","first-page":"20368","DOI":"10.1038\/s41598-020-74892-2","article-title":"Comprehensive assessment of TP53 loss of function using multiple combinatorial mutagenesis libraries","volume":"10","author":"Carbonnier","year":"2020","journal-title":"Sci Rep"},{"issue":"1","key":"2022031506230728800_ref34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13073-019-0690-2","article-title":"Recommendations for application of the functional evidence PS3\/BS3 criterion using the ACMG\/AMP sequence variant interpretation framework","volume":"12","author":"Brnich","year":"2019","journal-title":"Genome Med"},{"issue":"5","key":"2022031506230728800_ref35","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1093\/nar\/gkj518","article-title":"Computational approaches for predicting the biological effect of p53 missense mutations: a comparison of three sequence analysis based methods","volume":"34","author":"Mathe","year":"2006","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2022031506230728800_ref36","first-page":"516","article-title":"High prevalence of cancer-associated TP53 variants in the gnomAD database: a word of caution concerning the use of variant filtering","volume":"40","author":"Soussi","year":"2019","journal-title":"Hum Mutat"},{"issue":"5","key":"2022031506230728800_ref37","doi-asserted-by":"crossref","DOI":"10.1038\/s41418-020-00672-0","article-title":"Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene","volume":"28","author":"Doffe","year":"2021","journal-title":"Cell Death Differ"},{"issue":"1","key":"2022031506230728800_ref38","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/CCO.0000000000000423","article-title":"Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li-Fraumeni syndrome","volume":"30","author":"Amadou","year":"2018","journal-title":"Curr Opin Oncol"},{"issue":"8","key":"2022031506230728800_ref39","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1101\/gr.249599.119","article-title":"A pedigree-based prediction model identifies carriers of deleterious de novo mutations in families with Li-Fraumeni syndrome","volume":"30","author":"Gao","year":"2020","journal-title":"Genome Res"},{"issue":"2","key":"2022031506230728800_ref40","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1158\/0008-5472.CAN-19-0725","article-title":"Penetrance estimates over time to first and second primary cancer diagnosis in families with Li-Fraumeni syndrome: a single institution perspective","volume":"80","author":"Shin","year":"2020","journal-title":"Cancer Res"},{"issue":"23","key":"2022031506230728800_ref41","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1002\/cncr.30248","article-title":"Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort","volume":"122","author":"Mai","year":"2016","journal-title":"Cancer"},{"issue":"1","key":"2022031506230728800_ref42","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s10549-012-2375-z","article-title":"Prevalence of germline TP53 mutations in HER2+ breast cancer patients","volume":"139","author":"Rath","year":"2013","journal-title":"Breast Cancer Res Treat"},{"issue":"D1","key":"2022031506230728800_ref43","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: improving access to variant interpretations and supporting evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"15","key":"2022031506230728800_ref44","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1002\/j.1460-2075.1994.tb06656.x","article-title":"Analysis of the most representative tumour-derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation","volume":"13","author":"Ory","year":"1994","journal-title":"EMBO J"},{"issue":"7883","key":"2022031506230728800_ref45","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-021-04043-8","article-title":"Disease variant prediction with deep generative models of evolutionary data","volume":"599","author":"Frazer","year":"2021","journal-title":"Nature"},{"key":"2022031506230728800_ref46","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2021"},{"key":"2022031506230728800_ref47","first-page":"1","article-title":"Building Predictive Models in R Using the caret Package","volume-title":"J Stat Softw","author":"Kuhn","year":"2008"},{"issue":"5","key":"2022031506230728800_ref48","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1214\/aos\/1013203451","article-title":"Greedy function approximation: a gradient boosting machine","volume":"29","author":"Friedman","year":"2001","journal-title":"Ann Stat"},{"key":"2022031506230728800_ref49","first-page":"281","article-title":"Random search for hyper-parameter optimization","volume":"13","author":"Bergstra","year":"2012","journal-title":"J Machine Learn Res"},{"issue":"6","key":"2022031506230728800_ref50","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/humu.22552","article-title":"TP53 mutations in human cancer: database reassessment and prospects for the next decade","volume":"35","author":"Leroy","year":"2014","journal-title":"Hum Mutat"},{"issue":"11","key":"2022031506230728800_ref51","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1038\/ng.3414","article-title":"Intron retention is a widespread mechanism of tumor-suppressor inactivation","volume":"47","author":"Jung","year":"2015","journal-title":"Nat Genet"},{"issue":"3","key":"2022031506230728800_ref52","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.molcel.2010.02.037","article-title":"DNA binding cooperativity of p53 modulates the decision between cell-cycle arrest and apoptosis","volume":"38","author":"Schlereth","year":"2010","journal-title":"Mol Cell"},{"issue":"5","key":"2022031506230728800_ref53","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.celrep.2013.04.008","article-title":"p53 DNA binding cooperativity is essential for apoptosis and tumor suppression in vivo","volume":"3","author":"Timofeev","year":"2013","journal-title":"Cell Rep"},{"issue":"2","key":"2022031506230728800_ref54","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10689-016-9951-z","article-title":"Recurrent TP53 missense mutation in cancer patients of Arab descent","volume":"16","author":"Zick","year":"2017","journal-title":"Fam Cancer"},{"issue":"8","key":"2022031506230728800_ref55","first-page":"5182","article-title":"p53 domains: structure, oligomerization, and transformation","volume":"14","author":"Wang","year":"1994","journal-title":"Mol Cell Biol"},{"issue":"46","key":"2022031506230728800_ref56","doi-asserted-by":"crossref","first-page":"6976","DOI":"10.1038\/sj.onc.1208839","article-title":"The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library","volume":"24","author":"Kawaguchi","year":"2005","journal-title":"Oncogene"},{"issue":"4","key":"2022031506230728800_ref57","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/(SICI)1097-4644(20000315)76:4<572::AID-JCB6>3.0.CO;2-6","article-title":"Function, oligomerization, and conformation of tumor-associated p53 proteins with mutated C-terminus","volume":"76","author":"Atz","year":"2000","journal-title":"J Cell Biochem"},{"issue":"17","key":"2022031506230728800_ref58","doi-asserted-by":"crossref","first-page":"3732","DOI":"10.1158\/0008-5472.CAN-20-1390","article-title":"A rare TP53 mutation predominant in Ashkenazi Jews confers risk of multiple cancers","volume":"80","author":"Powers","year":"2020","journal-title":"Cancer Res"},{"issue":"4","key":"2022031506230728800_ref59","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":"Ioannidis","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"1","key":"2022031506230728800_ref60","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13073-017-0403-7","article-title":"Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation","volume":"9","author":"Kobayashi","year":"2017","journal-title":"Genome Med"},{"issue":"10","key":"2022031506230728800_ref61","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1136\/jmg.2008.058958","article-title":"High frequency of de novo mutations in Li-Fraumeni syndrome","volume":"46","author":"Gonzalez","year":"2009","journal-title":"J Med Genet"},{"issue":"3","key":"2022031506230728800_ref62","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1136\/jmedgenet-2017-104976","article-title":"Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome","volume":"55","author":"Renaux-Petel","year":"2018","journal-title":"J Med Genet"},{"issue":"Database issue","key":"2022031506230728800_ref63","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":"Landrum","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2022031506230728800_ref64","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/s41375-017-0007-7","article-title":"ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia-update on methodological approaches and results interpretation","volume":"32","author":"Malcikova","year":"2018","journal-title":"Leukemia"},{"issue":"4","key":"2022031506230728800_ref65","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"Dohner","year":"2017","journal-title":"Blood"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/23\/2\/bbab524\/42805629\/bbab524.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/23\/2\/bbab524\/42805629\/bbab524.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T06:26:41Z","timestamp":1647325601000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbab524\/6510957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,18]]},"references-count":65,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,3,10]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbab524","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,3]]},"published":{"date-parts":[[2022,1,18]]},"article-number":"bbab524"}}