{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:25:42Z","timestamp":1772519142987,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012902","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014008","name":"Ovarian Cancer Research Alliance","doi-asserted-by":"crossref","award":["Ann Schreiber Mentored Investigator Award [650687]"],"award-info":[{"award-number":["Ann Schreiber Mentored Investigator Award [650687]"]}],"id":[{"id":"10.13039\/100014008","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["Ruth L. Kirschstein National Research Service Award for Predoctoral Fellows [F31-CA271673]"],"award-info":[{"award-number":["Ruth L. Kirschstein National Research Service Award for Predoctoral Fellows [F31-CA271673]"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["Computational Biology Summer Program at Memorial Sloan Kettering Cancer Center [5R25CA233208-04]"],"award-info":[{"award-number":["Computational Biology Summer Program at Memorial Sloan Kettering Cancer Center [5R25CA233208-04]"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"\n Cancer development is characterized by chromosomal instability, manifesting in frequent occurrences of different genomic alteration mechanisms ranging in extent and impact. Mathematical modeling can help evaluate the role of each mutational process during tumor progression, however existing frameworks can only capture certain aspects of chromosomal instability (CIN). We present CINner, a mathematical framework for modeling genomic diversity and selection during tumor evolution. The main advantage of CINner is its flexibility to incorporate many genomic events that directly impact cellular fitness, from driver gene mutations to copy number alterations (CNAs), including focal amplifications and deletions, missegregations and whole-genome duplication (WGD). We apply CINner to find chromosome-arm selection parameters that drive tumorigenesis in the absence of WGD in chromosomally stable cancer types from the Pan-Cancer Analysis of Whole Genomes (PCAWG,\n \n \n \n \n \n n<\/mml:mi>\n =<\/mml:mo>\n 718<\/mml:mn>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n ). We found that the selection parameters predict WGD prevalence among different chromosomally unstable tumors, hinting that the selective advantage of WGD cells hinges on their tolerance for aneuploidy and escape from nullisomy. Analysis of inference results using CINner across cancer types in The Cancer Genome Atlas (\n \n \n \n \n \n n<\/mml:mi>\n =<\/mml:mo>\n 8207<\/mml:mn>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n ) further reveals that the inferred selection parameters reflect the bias between tumor suppressor genes and oncogenes on specific genomic regions. Direct application of CINner to model the WGD proportion and fraction of genome altered (FGA) in PCAWG uncovers the increase in CNA probabilities associated with WGD in each cancer type. CINner can also be utilized to study chromosomally stable cancer types, by applying a selection model based on driver gene mutations and focal amplifications or deletions (chronic lymphocytic leukemia in PCAWG,\n \n \n \n \n \n n<\/mml:mi>\n =<\/mml:mo>\n 95<\/mml:mn>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n ). Finally, we used CINner to analyze the impact of CNA probabilities, chromosome selection parameters, tumor growth dynamics and population size on cancer fitness and heterogeneity. We expect that CINner will provide a powerful modeling tool for the oncology community to quantify the impact of newly uncovered genomic alteration mechanisms on shaping tumor progression and adaptation.\n <\/jats:p>","DOI":"10.1371\/journal.pcbi.1012902","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T15:36:34Z","timestamp":1743694594000},"page":"e1012902","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["CINner: Modeling and simulation of chromosomal instability in cancer at single-cell resolution"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0010-4251","authenticated-orcid":true,"given":"Khanh N.","family":"Dinh","sequence":"first","affiliation":[]},{"given":"Ignacio","family":"V\u00e1zquez-Garc\u00eda","sequence":"additional","affiliation":[]},{"given":"Andrew","family":"Chan","sequence":"additional","affiliation":[]},{"given":"Rhea","family":"Malhotra","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-3606","authenticated-orcid":true,"given":"Adam","family":"Weiner","sequence":"additional","affiliation":[]},{"given":"Andrew W.","family":"McPherson","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-4952","authenticated-orcid":true,"given":"Simon","family":"Tavar\u00e9","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"issue":"6","key":"pcbi.1012902.ref001","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.cell.2018.08.027","article-title":"The multifaceted role of chromosomal instability in cancer and its microenvironment","volume":"174","author":"SF Bakhoum","year":"2018","journal-title":"Cell"},{"issue":"3","key":"pcbi.1012902.ref002","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrclinonc.2017.198","article-title":"Determinants and clinical implications of chromosomal instability in cancer","volume":"15","author":"L Sansregret","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"issue":"37","key":"pcbi.1012902.ref003","doi-asserted-by":"crossref","first-page":"60218","DOI":"10.18632\/oncotarget.11130","article-title":"DNA aneuploidy and breast cancer: a meta-analysis of 141,163 cases","volume":"7","author":"J Xu","year":"2016","journal-title":"Oncotarget"},{"issue":"9","key":"pcbi.1012902.ref004","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.neo.2021.06.003","article-title":"Genomic landscape and evolution of arm aneuploidy in lung adenocarcinoma","volume":"23","author":"B Gao","year":"2021","journal-title":"Neoplasia"},{"issue":"1","key":"pcbi.1012902.ref005","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3390\/biom13010092","article-title":"Ploidy status of ovarian cancer cell lines and their association with gene expression profiles","volume":"13","author":"M Du","year":"2023","journal-title":"Biomolecules"},{"issue":"2","key":"pcbi.1012902.ref006","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/MOH.0000000000000567","article-title":"Driver mutations in acute myeloid leukemia","volume":"27","author":"A Kishtagari","year":"2020","journal-title":"Curr Opin Hematol"},{"issue":"10","key":"pcbi.1012902.ref007","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.3390\/jcm8101675","article-title":"Mapping driver mutations to histopathological subtypes in papillary thyroid carcinoma: applying a deep convolutional neural network","volume":"8","author":"P Tsou","year":"2019","journal-title":"J Clin Med"},{"issue":"4","key":"pcbi.1012902.ref008","first-page":"2707","article-title":"Integrative analysis of cancer driver genes in prostate adenocarcinoma","volume":"19","author":"X Zhao","year":"2019","journal-title":"Mol Med Rep"},{"issue":"10","key":"pcbi.1012902.ref009","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":"G Ciriello","year":"2013","journal-title":"Nat Genet"},{"issue":"7762","key":"pcbi.1012902.ref010","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41586-019-1252-x","article-title":"Growth dynamics in naturally progressing chronic lymphocytic leukaemia","volume":"570","author":"M Gruber","year":"2019","journal-title":"Nature"},{"key":"pcbi.1012902.ref011","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-31641-3","volume-title":"Branching processes and their applications","author":"IM del Puerto","year":"2016"},{"issue":"1","key":"pcbi.1012902.ref012","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.mbs.2005.05.005","article-title":"A comprehensive continuous-time model for the appearance of CGH signal due to chromosomal missegregations during mitosis","volume":"197","author":"R Desper","year":"2005","journal-title":"Math Biosci"},{"issue":"15","key":"pcbi.1012902.ref013","doi-asserted-by":"crossref","first-page":"e2211687120","DOI":"10.1073\/pnas.2211687120","article-title":"A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains","volume":"120","author":"S Pompei","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pcbi.1012902.ref014","doi-asserted-by":"crossref","first-page":"11289","DOI":"10.1038\/s41598-022-14202-0","article-title":"Counting generations in birth and death processes with competing Erlang and exponential waiting times","volume":"12","author":"G Belluccini","year":"2022","journal-title":"Sci Rep"},{"issue":"25","key":"pcbi.1012902.ref015","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1021\/j100540a008","article-title":"Exact stochastic simulation of coupled chemical reactions","volume":"81","author":"DT Gillespie","year":"1977","journal-title":"J Phys Chem"},{"issue":"1","key":"pcbi.1012902.ref016","doi-asserted-by":"crossref","first-page":"e1-25","DOI":"10.1093\/sysbio\/syu081","article-title":"Cancer evolution: mathematical models and computational inference","volume":"64","author":"N Beerenwinkel","year":"2015","journal-title":"Syst Biol"},{"issue":"9","key":"pcbi.1012902.ref017","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/s41588-020-0675-5","article-title":"Subclonal reconstruction of tumors by using machine learning and population genetics","volume":"52","author":"G Caravagna","year":"2020","journal-title":"Nat Genet"},{"key":"pcbi.1012902.ref018","doi-asserted-by":"crossref","first-page":"e69799","DOI":"10.7554\/eLife.69799","article-title":"Quantifying chromosomal instability from intratumoral karyotype diversity using agent-based modeling and Bayesian inference","volume":"11","author":"AR Lynch","year":"2022","journal-title":"Elife"},{"issue":"9","key":"pcbi.1012902.ref019","doi-asserted-by":"crossref","first-page":"e1006447","DOI":"10.1371\/journal.pcbi.1006447","article-title":"A Markov chain for numerical chromosomal instability in clonally expanding populations","volume":"14","author":"S Elizalde","year":"2018","journal-title":"PLoS Comput Biol"},{"issue":"8","key":"pcbi.1012902.ref020","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/j.cell.2021.03.009","article-title":"Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes","volume":"184","author":"SC Dentro","year":"2021","journal-title":"Cell"},{"key":"pcbi.1012902.ref021","doi-asserted-by":"crossref","DOI":"10.1101\/2023.02.14.528596","article-title":"Predicting CIN rates from single-cell whole genome sequencing data using anin silicomodel","author":"B Bakker","year":"2023"},{"issue":"4","key":"pcbi.1012902.ref022","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.cell.2013.10.011","article-title":"Cumulative haploinsufficiency and triplosensitivity drive aneuploidy patterns and shape the cancer genome","volume":"155","author":"T Davoli","year":"2013","journal-title":"Cell"},{"issue":"7359","key":"pcbi.1012902.ref023","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":"7793","key":"pcbi.1012902.ref024","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41586-019-1907-7","article-title":"The evolutionary history of 2,658 cancers","volume":"578","author":"M Gerstung","year":"2020","journal-title":"Nature"},{"key":"pcbi.1012902.ref025","first-page":"2024.07.11.602772","article-title":"Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer","author":"A McPherson","year":"2024","journal-title":"bioRxiv"},{"issue":"9","key":"pcbi.1012902.ref026","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1158\/0008-5472.CAN-21-2065","article-title":"Whole-genome duplication shapes the aneuploidy landscape of human cancers","volume":"82","author":"K Prasad","year":"2022","journal-title":"Cancer Res"},{"issue":"7904","key":"pcbi.1012902.ref027","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41586-022-04578-4","article-title":"Genetic instability from a single S phase after whole-genome duplication","volume":"604","author":"S Gemble","year":"2022","journal-title":"Nature"},{"issue":"7543","key":"pcbi.1012902.ref028","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nature14187","article-title":"Polyploidy can drive rapid adaptation in yeast","volume":"519","author":"AM Selmecki","year":"2015","journal-title":"Nature"},{"issue":"4","key":"pcbi.1012902.ref029","doi-asserted-by":"crossref","first-page":"044109","DOI":"10.1063\/1.2159468","article-title":"Efficient step size selection for the tau-leaping simulation method","volume":"124","author":"Y Cao","year":"2006","journal-title":"J Chem Phys"},{"key":"pcbi.1012902.ref030","first-page":"208","article-title":"Ancestral inference for branching processes.","volume-title":"Branching processes in biology: variation, growth, extinction","author":"S. Tavar\u00e9","year":"2005"},{"issue":"1","key":"pcbi.1012902.ref031","article-title":"Statistical inference for the evolutionary history of cancer genomes","volume":"35","author":"KN Dinh","year":"2020","journal-title":"Statist Sci"},{"issue":"10","key":"pcbi.1012902.ref032","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1093\/bioinformatics\/bty867","article-title":"ABC random forests for Bayesian parameter inference","volume":"35","author":"L Raynal","year":"2019","journal-title":"Bioinformatics"},{"issue":"1","key":"pcbi.1012902.ref033","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1158\/2767-9764.CRC-22-0302","article-title":"Misaligned chromosomes are a major source of chromosomal instability in breast cancer","volume":"3","author":"JB Tucker","year":"2023","journal-title":"Cancer Res Commun"},{"issue":"22","key":"pcbi.1012902.ref034","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1016\/j.cub.2009.09.055","article-title":"Deviant kinetochore microtubule dynamics underlie chromosomal instability","volume":"19","author":"SF Bakhoum","year":"2009","journal-title":"Curr Biol"},{"issue":"4","key":"pcbi.1012902.ref035","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1083\/jcb.200712029","article-title":"Examining the link between chromosomal instability and aneuploidy in human cells","volume":"180","author":"SL Thompson","year":"2008","journal-title":"J Cell Biol"},{"issue":"2","key":"pcbi.1012902.ref036","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1109\/89.279278","article-title":"Maximum a posteriori estimation for multivariate Gaussian mixture observations of Markov chains","volume":"2","author":"J-L Gauvain","year":"1994","journal-title":"IEEE Trans Speech Audio Process"},{"issue":"7793","key":"pcbi.1012902.ref037","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":"ICGC\/TCGA Pan-Cancer Analysis of Whole Genomes Consortium","year":"2020","journal-title":"Nature"},{"issue":"5","key":"pcbi.1012902.ref038","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00401-018-1905-0","article-title":"Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDHwt astrocytoma to glioblastoma","volume":"136","author":"D Stichel","year":"2018","journal-title":"Acta Neuropathol"},{"key":"pcbi.1012902.ref039","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40478-015-0213-3","article-title":"DNA copy number analysis of Grade II-III and Grade IV gliomas reveals differences in molecular ontogeny including chromothripsis associated with IDH mutation status","volume":"3","author":"A Cohen","year":"2015","journal-title":"Acta Neuropathol Commun"},{"issue":"9","key":"pcbi.1012902.ref040","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/s41588-018-0179-8","article-title":"Copy number signatures and mutational processes in ovarian carcinoma","volume":"50","author":"G Macintyre","year":"2018","journal-title":"Nat Genet"},{"issue":"8","key":"pcbi.1012902.ref041","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1038\/bjc.2013.141","article-title":"DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas","volume":"108","author":"MM Kamieniak","year":"2013","journal-title":"Br J Cancer"},{"issue":"1","key":"pcbi.1012902.ref042","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1186\/s12885-023-11132-6","article-title":"Pan-cancer analysis of whole-genome doubling and its association with patient prognosis","volume":"23","author":"C Kikutake","year":"2023","journal-title":"BMC Cancer"},{"issue":"1","key":"pcbi.1012902.ref043","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41576-019-0171-x","article-title":"Context is everything: aneuploidy in cancer","volume":"21","author":"U Ben-David","year":"2020","journal-title":"Nat Rev Genet"},{"issue":"4","key":"pcbi.1012902.ref044","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.3390\/ijms24043733","article-title":"Whole-genome duplication and genome instability in cancer cells: double the trouble","volume":"24","author":"TY Lau","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pcbi.1012902.ref045","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41588-020-0584-7","article-title":"Interplay between whole-genome doubling and the accumulation of deleterious alterations in cancer evolution","volume":"52","author":"S L\u00f3pez","year":"2020","journal-title":"Nat Genet"},{"issue":"8","key":"pcbi.1012902.ref046","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/s41588-018-0165-1","article-title":"Genome doubling shapes the evolution and prognosis of advanced cancers","volume":"50","author":"CM Bielski","year":"2018","journal-title":"Nat Genet"},{"issue":"12","key":"pcbi.1012902.ref047","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.tips.2019.10.003","article-title":"Why Are Some Driver Mutations Rare?","volume":"40","author":"R Nussinov","year":"2019","journal-title":"Trends Pharmacol Sci"},{"issue":"5","key":"pcbi.1012902.ref048","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/s41588-024-01665-2","article-title":"Chromosome evolution screens recapitulate tissue-specific tumor aneuploidy patterns","volume":"56","author":"EV Watson","year":"2024","journal-title":"Nat Genet"},{"key":"pcbi.1012902.ref049","doi-asserted-by":"crossref","first-page":"1210983","DOI":"10.3389\/fcell.2023.1210983","article-title":"The fate of extra centrosomes in newly formed tetraploid cells: should I stay, or should I go?","volume":"11","author":"M Bloomfield","year":"2023","journal-title":"Front Cell Dev Biol"},{"issue":"11","key":"pcbi.1012902.ref050","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41568-018-0060-1","article-title":"The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers","volume":"18","author":"Z Sondka","year":"2018","journal-title":"Nat Rev Cancer"},{"issue":"5","key":"pcbi.1012902.ref051","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"D Hanahan","year":"2011","journal-title":"Cell"},{"issue":"10","key":"pcbi.1012902.ref052","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41568-020-0290-x","article-title":"A compendium of mutational cancer driver genes","volume":"20","author":"F Mart\u00ednez-Jim\u00e9nez","year":"2020","journal-title":"Nat Rev Cancer"},{"issue":"7938","key":"pcbi.1012902.ref053","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41586-022-05249-0","article-title":"Single-cell genomic variation induced by mutational processes in cancer","volume":"612","author":"T Funnell","year":"2022","journal-title":"Nature"},{"issue":"2","key":"pcbi.1012902.ref054","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1158\/2159-8290.CD-13-0285","article-title":"Tolerance of whole-genome doubling propagates chromosomal instability and accelerates cancer genome evolution","volume":"4","author":"SM Dewhurst","year":"2014","journal-title":"Cancer Discov"},{"issue":"3","key":"pcbi.1012902.ref055","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/s12276-021-00583-1","article-title":"High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer","volume":"53","author":"JE Kim","year":"2021","journal-title":"Exp Mol Med"},{"issue":"11","key":"pcbi.1012902.ref056","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1038\/s41588-021-00949-1","article-title":"The context-specific role of germline pathogenicity in tumorigenesis","volume":"53","author":"P Srinivasan","year":"2021","journal-title":"Nat Genet"},{"issue":"2","key":"pcbi.1012902.ref057","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.cels.2021.10.001","article-title":"Allele-specific genomic data elucidate the role of somatic gain and copy-number neutral loss of heterozygosity in cancer","volume":"13","author":"Y Ciani","year":"2022","journal-title":"Cell Syst"},{"issue":"6660","key":"pcbi.1012902.ref058","doi-asserted-by":"crossref","first-page":"eadg4521","DOI":"10.1126\/science.adg4521","article-title":"Oncogene-like addiction to aneuploidy in human cancers","volume":"381","author":"V Girish","year":"2023","journal-title":"Science"},{"issue":"8","key":"pcbi.1012902.ref059","doi-asserted-by":"crossref","first-page":"e1008340","DOI":"10.1371\/journal.pgen.1008340","article-title":"An estimator of first coalescent time reveals selection on young variants and large heterogeneity in rare allele ages among human populations","volume":"15","author":"A Platt","year":"2019","journal-title":"PLoS Genet"},{"issue":"1\u20132","key":"pcbi.1012902.ref060","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0895-7177(00)00122-9","article-title":"A stochastic model of chromosome segregation errors with reference to cancer cells","volume":"32","author":"Y Gusev","year":"2000","journal-title":"Math Comput Model"},{"issue":"12\u201313","key":"pcbi.1012902.ref061","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/S0895-7177(00)00313-7","article-title":"Long-term dynamics of chromosomal instability in cancer: A transition probability model","volume":"33","author":"Y Gusev","year":"2001","journal-title":"Math Comput Model"},{"issue":"7853","key":"pcbi.1012902.ref062","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41586-021-03357-x","article-title":"Breast tumours maintain a reservoir of subclonal diversity during expansion","volume":"592","author":"DC Minussi","year":"2021","journal-title":"Nature"},{"issue":"7916","key":"pcbi.1012902.ref063","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1038\/s41586-022-04789-9","article-title":"A pan-cancer compendium of chromosomal instability","volume":"606","author":"RM Drews","year":"2022","journal-title":"Nature"},{"key":"pcbi.1012902.ref064","volume-title":"CIN signature genome simulation: Simulating mutational processes to benchmark feature-based copy number signatures"},{"issue":"5","key":"pcbi.1012902.ref065","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/molbev\/msaa025","article-title":"Cell coal: coalescent simulation of single-cell sequencing samples","volume":"37","author":"D Posada","year":"2020","journal-title":"Mol Biol Evol"},{"issue":"7","key":"pcbi.1012902.ref066","doi-asserted-by":"crossref","first-page":"e1008012","DOI":"10.1371\/journal.pcbi.1008012","article-title":"Assessing the performance of methods for copy number aberration detection from single-cell DNA sequencing data","volume":"16","author":"XF Mallory","year":"2020","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"pcbi.1012902.ref067","doi-asserted-by":"crossref","first-page":"e1010815","DOI":"10.1371\/journal.pcbi.1010815","article-title":"Intra-tumor heterogeneity, turnover rate and karyotype space shape susceptibility to missegregation-induced extinction","volume":"19","author":"GJ Kimmel","year":"2023","journal-title":"PLoS Comput Biol"},{"issue":"5","key":"pcbi.1012902.ref068","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.celrep.2015.06.065","article-title":"Dynamics of Tumor Heterogeneity Derived from Clonal Karyotypic Evolution","volume":"12","author":"AM Laughney","year":"2015","journal-title":"Cell Rep"},{"key":"pcbi.1012902.ref069","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1038\/srep02650","article-title":"Comprehensive identification of mutational cancer driver genes across 12 tumor types","volume":"3","author":"D Tamborero","year":"2013","journal-title":"Sci Rep"},{"issue":"7954","key":"pcbi.1012902.ref070","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/s41586-023-05794-2","article-title":"Whole-genome doubling drives oncogenic loss of chromatin segregation","volume":"615","author":"RA Lambuta","year":"2023","journal-title":"Nature"},{"issue":"5","key":"pcbi.1012902.ref071","doi-asserted-by":"crossref","first-page":"1207-1221.e22","DOI":"10.1016\/j.cell.2019.10.026","article-title":"Clonal decomposition and DNA replication states defined by scaled single-cell genome sequencing","volume":"179","author":"E Laks","year":"2019","journal-title":"Cell"},{"issue":"7868","key":"pcbi.1012902.ref072","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-021-03648-3","article-title":"Clonal fitness inferred from time-series modelling of single-cell cancer genomes","volume":"595","author":"S Salehi","year":"2021","journal-title":"Nature"},{"issue":"1","key":"pcbi.1012902.ref073","doi-asserted-by":"crossref","first-page":"17699","DOI":"10.1038\/s41598-024-67842-9","article-title":"Inference of chromosome selection parameters and missegregation rate in cancer from DNA-sequencing data","volume":"14","author":"Z Xiang","year":"2024","journal-title":"Sci Rep"},{"issue":"7848","key":"pcbi.1012902.ref074","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41586-020-03064-z","article-title":"Chromothripsis drives the evolution of gene amplification in cancer","volume":"591","author":"O Shoshani","year":"2021","journal-title":"Nature"},{"issue":"1","key":"pcbi.1012902.ref075","doi-asserted-by":"crossref","first-page":"5327","DOI":"10.1038\/s41467-020-19119-8","article-title":"Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics","volume":"11","author":"K Morita","year":"2020","journal-title":"Nat Commun"},{"issue":"7834","key":"pcbi.1012902.ref076","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41586-020-2864-x","article-title":"Single-cell mutation analysis of clonal evolution in myeloid malignancies","volume":"587","author":"LA Miles","year":"2020","journal-title":"Nature"},{"issue":"11","key":"pcbi.1012902.ref077","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":"Nat Rev Genet"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1012902","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012902","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T13:34:47Z","timestamp":1744378487000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012902"}},"subtitle":[],"editor":[{"given":"Simone","family":"Zaccaria,","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":77,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1012902","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.04.03.587939","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]}}}