{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:19:29Z","timestamp":1772173169895,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010815","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R00CA215256"],"award-info":[{"award-number":["R00CA215256"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["1R37CA266727-01A1"],"award-info":[{"award-number":["1R37CA266727-01A1"]}]},{"name":"National Cancer Institute","award":["P30-CA076292"],"award-info":[{"award-number":["P30-CA076292"]}]},{"name":"Moffitt Cancer Center Evolutionary Therapy Center of Excellence","award":["CET 30-20458-03-20"],"award-info":[{"award-number":["CET 30-20458-03-20"]}]},{"name":"Richard O. Jacobson Foundation"},{"name":"William G. \u2019Bill\u2019 Bankhead Jr and David Coley Cancer Research Program","award":["20B06"],"award-info":[{"award-number":["20B06"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The phenotypic efficacy of somatic copy number alterations (SCNAs) stems from their incidence per base pair of the genome, which is orders of magnitudes greater than that of point mutations. One mitotic event stands out in its potential to significantly change a cell\u2019s SCNA burden\u2013a chromosome missegregation. A stochastic model of chromosome mis-segregations has been previously developed to describe the evolution of SCNAs of a single chromosome type. Building upon this work, we derive a general deterministic framework for modeling missegregations of multiple chromosome types. The framework offers flexibility to model intra-tumor heterogeneity in the SCNAs of all chromosomes, as well as in missegregation- and turnover rates. The model can be used to test how selection acts upon coexisting karyotypes over hundreds of generations. We use the model to calculate missegregation-induced population extinction (MIE) curves, that separate viable from non-viable populations as a function of their turnover- and missegregation rates. Turnover- and missegregation rates estimated from scRNA-seq data are then compared to theoretical predictions. We find convergence of theoretical and empirical results in both the location of MIE curves and the necessary conditions for MIE. When a dependency of missegregation rate on karyotype is introduced, karyotypes associated with low missegregation rates act as a stabilizing refuge, rendering MIE impossible unless turnover rates are exceedingly high. Intra-tumor heterogeneity, including heterogeneity in missegregation rates, increases as tumors progress, rendering MIE unlikely.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010815","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T13:36:31Z","timestamp":1674480991000},"page":"e1010815","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Intra-tumor heterogeneity, turnover rate and karyotype space shape susceptibility to missegregation-induced extinction"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9766-5399","authenticated-orcid":true,"given":"Gregory J.","family":"Kimmel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Beck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8411-9911","authenticated-orcid":true,"given":"Thomas","family":"Veith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Bakhoum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7731-3345","authenticated-orcid":true,"given":"Philipp M.","family":"Altrock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2469-5180","authenticated-orcid":true,"given":"Noemi","family":"Andor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"issue":"1","key":"pcbi.1010815.ref001","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1054\/bjoc.2001.1892","article-title":"Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data","volume":"85","author":"D Choma","year":"2001","journal-title":"British journal of cancer"},{"issue":"3","key":"pcbi.1010815.ref002","doi-asserted-by":"crossref","first-page":"506","DOI":"10.4103\/0973-1482.137927","article-title":"Breast cancer statistics and markers","volume":"10","author":"MS Donepudi","year":"2014","journal-title":"Journal of cancer research and therapeutics"},{"issue":"7","key":"pcbi.1010815.ref003","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1136\/gut.2007.135004","article-title":"Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis","volume":"57","author":"A Walther","year":"2008","journal-title":"Gut"},{"issue":"11","key":"pcbi.1010815.ref004","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1158\/1078-0432.CCR-15-0635","article-title":"The combination of DNA ploidy status and PTEN\/6q15 deletions provides strong and independent prognostic information in prostate cancer","volume":"22","author":"M Lennartz","year":"2016","journal-title":"Clinical Cancer Research"},{"issue":"2","key":"pcbi.1010815.ref005","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00401-013-1196-4","article-title":"Glioblastomas are composed of genetically divergent clones with distinct tumourigenic potential and variable stem cell-associated phenotypes","volume":"127","author":"D Stieber","year":"2014","journal-title":"Acta neuropathologica"},{"issue":"4","key":"pcbi.1010815.ref006","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":"The Journal of Cell Biology"},{"issue":"11","key":"pcbi.1010815.ref007","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1158\/2159-8290.CD-14-0403","article-title":"DNA-damage response during mitosis induces whole-chromosome missegregation","volume":"4","author":"SF Bakhoum","year":"2014","journal-title":"Cancer Discovery"},{"issue":"4","key":"pcbi.1010815.ref008","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nsmb.2245","article-title":"A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest","volume":"19","author":"MT Hayashi","year":"2012","journal-title":"Nature Structural & Molecular Biology"},{"issue":"4","key":"pcbi.1010815.ref009","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1083\/jcb.201502107","article-title":"TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells","volume":"210","author":"RT Pedersen","year":"2015","journal-title":"The Journal of Cell Biology"},{"issue":"7581","key":"pcbi.1010815.ref010","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/nature16139","article-title":"Replication stress activates DNA repair synthesis in mitosis","volume":"528","author":"S Minocherhomji","year":"2015","journal-title":"Nature"},{"issue":"3","key":"pcbi.1010815.ref011","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.trecan.2017.02.001","article-title":"Mitotic DNA Damage Response: At the Crossroads of Structural and Numerical Cancer Chromosome Instabilities","volume":"3","author":"SF Bakhoum","year":"2017","journal-title":"Trends in Cancer"},{"issue":"2","key":"pcbi.1010815.ref012","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ccell.2016.12.004","article-title":"Single-chromosome Gains Commonly Function as Tumor Suppressors","volume":"31","author":"JM Sheltzer","year":"2017","journal-title":"Cancer Cell"},{"issue":"7252","key":"pcbi.1010815.ref013","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nature08136","article-title":"A mechanism linking extra centrosomes to chromosomal instability","volume":"460","author":"NJ Ganem","year":"2009","journal-title":"Nature"},{"issue":"8","key":"pcbi.1010815.ref014","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/ncb2994","article-title":"Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells","volume":"16","author":"N Ertych","year":"2014","journal-title":"Nature Cell Biology"},{"issue":"1","key":"pcbi.1010815.ref015","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ncb1809","article-title":"Genome stability is ensured by temporal control of kinetochore-microtubule dynamics","volume":"11","author":"SF Bakhoum","year":"2009","journal-title":"Nature Cell Biology"},{"issue":"1","key":"pcbi.1010815.ref016","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ceb.2011.11.012","article-title":"Kinetochores and disease: keeping microtubule dynamics in check!","volume":"24","author":"SF Bakhoum","year":"2012","journal-title":"Current Opinion in Cell Biology"},{"issue":"2","key":"pcbi.1010815.ref017","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/bcp.13126","article-title":"Microtubule destabilising agents: far more than just antimitotic anticancer drugs","volume":"83","author":"D Bates","year":"2017","journal-title":"British Journal of Clinical Pharmacology"},{"issue":"1","key":"pcbi.1010815.ref018","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/mutage\/17.1.83","article-title":"Influence of donor age on vinblastine-induced chromosome malsegregation in cultured peripheral lymphocytes","volume":"17","author":"P Leopardi","year":"2002","journal-title":"Mutagenesis"},{"issue":"4","key":"pcbi.1010815.ref019","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1158\/0008-5472.CAN-15-1617","article-title":"Effects of Anticancer Drugs on Chromosome Instability and New Clinical Implications for Tumor-Suppressing Therapies","volume":"76","author":"HS Lee","year":"2016","journal-title":"Cancer Research"},{"key":"pcbi.1010815.ref020","doi-asserted-by":"crossref","first-page":"5990","DOI":"10.1038\/ncomms6990","article-title":"Numerical chromosomal instability mediates susceptibility to radiation treatment","volume":"6","author":"SF Bakhoum","year":"2015","journal-title":"Nature Communications"},{"issue":"5","key":"pcbi.1010815.ref021","doi-asserted-by":"crossref","first-page":"e63054","DOI":"10.1371\/journal.pone.0063054","article-title":"Tumor environmental factors glucose deprivation and lactic acidosis induce mitotic chromosomal instability-an implication in aneuploid human tumors","volume":"8","author":"C Dai","year":"2013","journal-title":"PLoS One"},{"issue":"11","key":"pcbi.1010815.ref022","doi-asserted-by":"crossref","first-page":"e80349","DOI":"10.1371\/journal.pone.0080349","article-title":"Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment","volume":"8","author":"M Kondoh","year":"2013","journal-title":"PloS one"},{"issue":"2","key":"pcbi.1010815.ref023","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 Discovery"},{"issue":"7061","key":"pcbi.1010815.ref024","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nature04217","article-title":"Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells","volume":"437","author":"T Fujiwara","year":"2005","journal-title":"Nature"},{"issue":"4","key":"pcbi.1010815.ref025","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1089\/thy.2012.0614","article-title":"Intratumor BRAFV600E heterogeneity and kinase inhibitors in the treatment of thyroid cancer: a call for participation","volume":"23","author":"M Vitale","year":"2013","journal-title":"Thyroid: official journal of the American Thyroid Association"},{"issue":"4","key":"pcbi.1010815.ref026","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1172\/JCI59954","article-title":"Chromosomal instability and cancer: a complex relationship with therapeutic potential","volume":"122","author":"SF Bakhoum","year":"2012","journal-title":"The Journal of Clinical Investigation"},{"issue":"3","key":"pcbi.1010815.ref027","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1083\/jcb.200905057","article-title":"Proliferation of aneuploid human cells is limited by a p53-dependent mechanism","volume":"188","author":"SL Thompson","year":"2010","journal-title":"The Journal of Cell Biology"},{"issue":"6","key":"pcbi.1010815.ref028","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.devcel.2017.05.022","article-title":"Chromosome mis-segregation generates cell cycle-arrested cells with complex karyotypes that are eliminated by the immune system","volume":"41","author":"S Santaguida","year":"2017","journal-title":"Developmental cell"},{"issue":"10","key":"pcbi.1010815.ref029","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1158\/1055-9965.EPI-11-0343","article-title":"Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer","volume":"20","author":"R Roylance","year":"2011","journal-title":"Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology"},{"issue":"10","key":"pcbi.1010815.ref030","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1158\/0008-5472.CAN-10-3667","article-title":"Paradoxical relationship between chromosomal instability and survival outcome in cancer","volume":"71","author":"NJ Birkbak","year":"2011","journal-title":"Cancer research"},{"issue":"1","key":"pcbi.1010815.ref031","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":"Mathematical and Computer Modelling"},{"issue":"12","key":"pcbi.1010815.ref032","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":"Mathematical and Computer Modelling"},{"issue":"9","key":"pcbi.1010815.ref033","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 computational biology"},{"issue":"5","key":"pcbi.1010815.ref034","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 Reports"},{"key":"pcbi.1010815.ref035","doi-asserted-by":"crossref","first-page":"0","DOI":"10.1093\/oso\/9780198851875.001.0001","volume-title":"The Equations of Materials","author":"B Cantor","year":"2020"},{"key":"pcbi.1010815.ref036","volume-title":"Ger\u0161gorin and his circles","author":"RS Varga","year":"2010"},{"issue":"D1","key":"pcbi.1010815.ref037","doi-asserted-by":"crossref","first-page":"D1420","DOI":"10.1093\/nar\/gkaa1020","article-title":"TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment","volume":"49","author":"D Sun","year":"2021","journal-title":"Nucleic Acids Research"},{"issue":"1","key":"pcbi.1010815.ref038","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1038\/s41467-020-17186-5","article-title":"Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy","volume":"11","author":"CP Couturier","year":"2020","journal-title":"Nature Communications"},{"key":"pcbi.1010815.ref039","first-page":"6653793","article-title":"Identification of Tumor Tissue of Origin with RNA-Seq Data and Using Gradient Boosting Strategy","volume":"2021","author":"R Li","year":"2021","journal-title":"BioMed Research International"},{"issue":"1","key":"pcbi.1010815.ref040","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41598-017-18310-0","article-title":"Radiogenomic analysis of hypoxia pathway is predictive of overall survival in Glioblastoma","volume":"8","author":"N Beig","year":"2018","journal-title":"Scientific Reports"},{"issue":"6","key":"pcbi.1010815.ref041","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/modpathol.2016.60","article-title":"Pan-cancer transcriptome analysis reveals a gene expression signature for the identification of tumor tissue origin","volume":"29","author":"Q Xu","year":"2016","journal-title":"Modern Pathology"},{"key":"pcbi.1010815.ref042","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s13059-016-1064-3","article-title":"Correlation of an epigenetic mitotic clock with cancer risk","volume":"17","author":"Z Yang","year":"2016","journal-title":"Genome Biology"},{"key":"pcbi.1010815.ref043","article-title":"Joint single cell DNA-seq and RNA-seq of gastric cancer cell lines reveals rules of in vitro evolution","author":"N Andor","year":"2020","journal-title":"NAR Genomics and Bioinformatics"},{"issue":"1","key":"pcbi.1010815.ref044","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ccr.2009.12.020","article-title":"Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1","volume":"17","author":"RGW Verhaak","year":"2010","journal-title":"Cancer cell"},{"issue":"7718","key":"pcbi.1010815.ref045","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41586-018-0409-3","article-title":"Genetic and transcriptional evolution alters cancer cell line drug response","volume":"560","author":"U Ben-David","year":"2018","journal-title":"Nature"},{"issue":"11","key":"pcbi.1010815.ref046","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1038\/ng.3967","article-title":"Patient-derived xenografts undergo mouse-specific tumor evolution","volume":"49","author":"U Ben-David","year":"2017","journal-title":"Nature Genetics"},{"issue":"1","key":"pcbi.1010815.ref047","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-Seq data","volume":"14","author":"S H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"issue":"Database issue","key":"pcbi.1010815.ref048","doi-asserted-by":"crossref","first-page":"D472","DOI":"10.1093\/nar\/gkt1102","article-title":"The Reactome pathway knowledgebase","volume":"42","author":"D Croft","year":"2014","journal-title":"Nucleic Acids Research"},{"issue":"4","key":"pcbi.1010815.ref049","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1053\/ejso.1999.0907","article-title":"Cell production rates in human tissues and tumours and their significance. Part II: clinical data","volume":"26","author":"D Rew","year":"2000","journal-title":"European Journal of Surgical Oncology (EJSO)"},{"issue":"12","key":"pcbi.1010815.ref050","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/0959-8049(94)00252-Z","article-title":"In vivo cell kinetic measurements in human oesophageal cancer: what can be learned from multiple biopsies?","volume":"30","author":"K Haustermans","year":"1994","journal-title":"European Journal of Cancer"},{"issue":"5","key":"pcbi.1010815.ref051","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1177\/0284185113475923","article-title":"Evaluation of the growth pattern of carcinoma of colon and rectum by MDCT","volume":"54","author":"SJ Choi","year":"2013","journal-title":"Acta Radiologica"},{"issue":"5","key":"pcbi.1010815.ref052","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2176\/nmc.35.289","article-title":"Growth rate of intracranial meningioma: tumor doubling time and proliferating cell nuclear antigen staining index","volume":"35","author":"M IDE","year":"1995","journal-title":"Neurologia medico-chirurgica"},{"issue":"2","key":"pcbi.1010815.ref053","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1097\/00000658-198308000-00007","article-title":"Carcinoma of the colon and rectum-growth rate","volume":"198","author":"S Bolin","year":"1983","journal-title":"Annals of surgery"},{"key":"pcbi.1010815.ref054","unstructured":"Margolese R, HG BT. Natural history and prognostic markers. Holland-Frei Cancer Medicine 6th edition ed Hamilton (ON): BC Decker. 2003;."},{"issue":"1","key":"pcbi.1010815.ref055","first-page":"21","article-title":"The rate of tumor growth and cell loss in cervical cancer","volume":"35","author":"G Zharinov","year":"1989","journal-title":"Voprosy onkologii"},{"issue":"4","key":"pcbi.1010815.ref056","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1097\/00000372-200308000-00003","article-title":"Tumor doubling time of cutaneous melanoma and its metastasis","volume":"25","author":"JA Carlson","year":"2003","journal-title":"The American journal of dermatopathology"},{"key":"pcbi.1010815.ref057","first-page":"CMO","article-title":"Small cell lung cancer doubling time and its effect on clinical presentation: a concise review","volume":"6","author":"K Harris","year":"2012","journal-title":"Clinical Medicine Insights: Oncology"},{"issue":"2","key":"pcbi.1010815.ref058","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s11538-013-9925-3","article-title":"Modelling lymphoma therapy and outcome","volume":"76","author":"K Roesch","year":"2014","journal-title":"Bulletin of mathematical biology"},{"issue":"7689","key":"pcbi.1010815.ref059","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature25432","article-title":"Chromosomal instability drives metastasis through a cytosolic DNA response","volume":"553","author":"SF Bakhoum","year":"2018","journal-title":"Nature"},{"issue":"6121","key":"pcbi.1010815.ref060","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway","volume":"339","author":"L Sun","year":"2013","journal-title":"Science (New York, NY)"},{"issue":"1","key":"pcbi.1010815.ref061","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.celrep.2014.08.074","article-title":"Dnase2a deficiency uncovers lysosomal clearance of damaged nuclear DNA via autophagy","volume":"9","author":"YY Lan","year":"2014","journal-title":"Cell Reports"},{"issue":"7668","key":"pcbi.1010815.ref062","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nature23449","article-title":"cGAS surveillance of micronuclei links genome instability to innate immunity","volume":"548","author":"KJ Mackenzie","year":"2017","journal-title":"Nature"},{"issue":"1","key":"pcbi.1010815.ref063","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":"Nature Reviews Genetics"},{"issue":"3","key":"pcbi.1010815.ref064","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nbt.2514","article-title":"Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples","volume":"31","author":"K Cibulskis","year":"2013","journal-title":"Nature Biotechnology"},{"issue":"23","key":"pcbi.1010815.ref065","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.1242\/jcs.039537","article-title":"The consequences of tetraploidy and aneuploidy","volume":"121","author":"Z Storchova","year":"2008","journal-title":"Journal of Cell Science"},{"issue":"1","key":"pcbi.1010815.ref066","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/s41467-020-14286-0","article-title":"Chromosome arm aneuploidies shape tumour evolution and drug response","volume":"11","author":"A Shukla","year":"2020","journal-title":"Nature Communications"},{"issue":"7868","key":"pcbi.1010815.ref067","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 S","year":"2021","journal-title":"Nature"},{"issue":"3","key":"pcbi.1010815.ref068","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.cell.2022.01.003","article-title":"Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients","volume":"185","author":"B Nguyen","year":"2022","journal-title":"Cell"},{"issue":"7655","key":"pcbi.1010815.ref069","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature22364","article-title":"Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution","volume":"545","author":"C Abbosh","year":"2017","journal-title":"Nature"},{"issue":"22","key":"pcbi.1010815.ref070","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1056\/NEJMoa1616288","article-title":"Tracking the Evolution of Non-Small-Cell Lung Cancer","volume":"376","author":"M Jamal-Hanjani","year":"2017","journal-title":"The New England Journal of Medicine"},{"key":"pcbi.1010815.ref071","article-title":"Tipping cancer cells over the edge: the context-dependent cost of high ploidy","author":"Noemi Andor","year":"2021","journal-title":"Cancer Research"},{"issue":"3","key":"pcbi.1010815.ref072","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s41559-018-0768-z","article-title":"Fibroblasts and alectinib switch the evolutionary games played by non-small cell lung cancer","volume":"3","author":"A Kaznatcheev","year":"2019","journal-title":"Nature Ecology & Evolution"},{"key":"pcbi.1010815.ref073","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":"5","key":"pcbi.1010815.ref074","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41587-020-00795-2","article-title":"Delineating copy number and clonal substructure in human tumors from single-cell transcriptomes","volume":"39","author":"R Gao","year":"2021","journal-title":"Nature Biotechnology"},{"issue":"1","key":"pcbi.1010815.ref075","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41591-020-01182-9","article-title":"The distribution of cellular turnover in the human body","volume":"27","author":"R Sender","year":"2021","journal-title":"Nature Medicine"},{"issue":"1","key":"pcbi.1010815.ref076","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1038\/s41467-017-01355-0","article-title":"Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors","volume":"8","author":"J Cheng","year":"2017","journal-title":"Nature Communications"},{"issue":"1","key":"pcbi.1010815.ref077","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13073-019-0643-9","article-title":"Associating somatic mutations to clinical outcomes: a pan-cancer study of survival time","volume":"11","author":"P Little","year":"2019","journal-title":"Genome Medicine"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1010815","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1010815","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T02:36:34Z","timestamp":1701743794000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1010815"}},"subtitle":[],"editor":[{"given":"Mohammed","family":"El-Kebir","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,23]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1010815","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.11.03.466486","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,23]]}}}