{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T15:22:04Z","timestamp":1776698524379,"version":"3.51.2"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010677","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000}}],"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>As a cancer develops, its cells accrue new mutations, resulting in a heterogeneous, complex genomic profile. We make use of this heterogeneity to derive simple, analytic estimates of parameters driving carcinogenesis and reconstruct the timeline of selective events following initiation of an individual cancer, where two longitudinal samples are available for sequencing. Using stochastic computer simulations of cancer growth, we show that we can accurately estimate mutation rate, time before and after a driver event occurred, and growth rates of both initiated cancer cells and subsequently appearing subclones. We demonstrate that in order to obtain accurate estimates of mutation rate and timing of events, observed mutation counts should be corrected to account for clonal mutations that occurred after the founding of the tumor, as well as sequencing coverage. Chronic lymphocytic leukemia (CLL), which often does not require treatment for years after diagnosis, presents an optimal system to study the untreated, natural evolution of cancer cell populations. When we apply our methodology to reconstruct the individual evolutionary histories of CLL patients, we find that the parental leukemic clone typically appears within the first fifteen years of life.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010677","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T17:36:33Z","timestamp":1667583393000},"page":"e1010677","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Inferring parameters of cancer evolution in chronic lymphocytic leukemia"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8761-0829","authenticated-orcid":true,"given":"Nathan D.","family":"Lee","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2761-825X","authenticated-orcid":true,"given":"Ivana","family":"Bozic","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"issue":"4260","key":"pcbi.1010677.ref001","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1126\/science.959840","article-title":"The Clonal Evolution of Tumor Cell Populations","volume":"194","author":"PC Nowell","year":"1976","journal-title":"Science"},{"issue":"7239","key":"pcbi.1010677.ref002","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nature07943","article-title":"The cancer genome","volume":"458","author":"MR Stratton","year":"2009","journal-title":"Nature"},{"issue":"5","key":"pcbi.1010677.ref003","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":"2","key":"pcbi.1010677.ref004","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.cell.2018.02.060","article-title":"Comprehensive Characterization of Cancer Driver Genes and Mutations","volume":"173","author":"MH Bailey","year":"2018","journal-title":"Cell"},{"issue":"3","key":"pcbi.1010677.ref005","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/ng.3489","article-title":"Identification of neutral tumor evolution across cancer types","volume":"48","author":"MJ Williams","year":"2016","journal-title":"Nature Genetics"},{"issue":"5129","key":"pcbi.1010677.ref006","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/217624a0","article-title":"Evolutionary Rate at the Molecular Level","volume":"217","author":"M Kimura","year":"1968","journal-title":"Nature"},{"issue":"3","key":"pcbi.1010677.ref007","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1017\/S0016672300011459","article-title":"Genetic variability maintained in a finite population due to mutational production of neutral and nearly neutral isoalleles*","volume":"11","author":"M Kimura","year":"1968","journal-title":"Genetics Research"},{"issue":"1","key":"pcbi.1010677.ref008","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1017\/S0016672300014634","article-title":"The hitch-hiking effect of a favourable gene","volume":"23","author":"JM Smith","year":"1974","journal-title":"Genetics Research"},{"issue":"7","key":"pcbi.1010677.ref009","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41576-019-0114-6","article-title":"Resolving genetic heterogeneity in cancer","volume":"20","author":"S Turajlic","year":"2019","journal-title":"Nature Reviews Genetics"},{"issue":"6127","key":"pcbi.1010677.ref010","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1126\/science.1235122","article-title":"Cancer Genome Landscapes","volume":"339","author":"B Vogelstein","year":"2013","journal-title":"Science"},{"issue":"7457","key":"pcbi.1010677.ref011","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature12213","article-title":"Mutational heterogeneity in cancer and the search for new cancer-associated genes","volume":"499","author":"MS Lawrence","year":"2013","journal-title":"Nature"},{"issue":"12","key":"pcbi.1010677.ref012","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/nrc2013","article-title":"Cancer as an evolutionary and ecological process","volume":"6","author":"LMF Merlo","year":"2006","journal-title":"Nature Reviews Cancer"},{"issue":"1","key":"pcbi.1010677.ref013","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1752-4571.2008.00063.x","article-title":"SYNTHESIS: Cancer research meets evolutionary biology","volume":"2","author":"JW Pepper","year":"2009","journal-title":"Evolutionary Applications"},{"issue":"3","key":"pcbi.1010677.ref014","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1073\/pnas.97.3.1236","article-title":"Genetic reconstruction of individual colorectal tumor histories","volume":"97","author":"JL Tsao","year":"2000","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"11","key":"pcbi.1010677.ref015","doi-asserted-by":"crossref","first-page":"4283","DOI":"10.1073\/pnas.0712345105","article-title":"Comparative lesion sequencing provides insights into tumor evolution","volume":"105","author":"S Jones","year":"2008","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"7319","key":"pcbi.1010677.ref016","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/nature09515","article-title":"Distant metastasis occurs late during the genetic evolution of pancreatic cancer","volume":"467","author":"S Yachida","year":"2010","journal-title":"Nature"},{"issue":"18","key":"pcbi.1010677.ref017","doi-asserted-by":"crossref","first-page":"E1889","DOI":"10.1073\/pnas.1400179111","article-title":"Hypermutable DNA chronicles the evolution of human colon cancer","volume":"111","author":"K Naxerova","year":"2014","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"283","key":"pcbi.1010677.ref018","doi-asserted-by":"crossref","first-page":"283ra54","DOI":"10.1126\/scitranslmed.aaa1408","article-title":"Clonal status of actionable driver events and the timing of mutational processes in cancer evolution","volume":"7","author":"N McGranahan","year":"2015","journal-title":"Science Translational Medicine"},{"issue":"3","key":"pcbi.1010677.ref019","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.cell.2018.02.020","article-title":"Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal","volume":"173","author":"TJ Mitchell","year":"2018","journal-title":"Cell"},{"issue":"7793","key":"pcbi.1010677.ref020","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":"PCAWG Evolution & Heterogeneity Working Group, PCAWG Consortium","year":"2020","journal-title":"Nature"},{"issue":"1","key":"pcbi.1010677.ref021","doi-asserted-by":"crossref","first-page":"e1008400","DOI":"10.1371\/journal.pcbi.1008400","article-title":"Reconstructing tumor evolutionary histories and clone trees in polynomial-time with SubMARine","volume":"17","author":"LK Sundermann","year":"2021","journal-title":"PLOS Computational Biology"},{"issue":"1","key":"pcbi.1010677.ref022","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41467-020-14352-7","article-title":"Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig","volume":"11","author":"PCAWG Evolution and Heterogeneity Working Group, PCAWG Consortium","year":"2020","journal-title":"Nature Communications"},{"issue":"2","key":"pcbi.1010677.ref023","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.scr.2015.01.005","article-title":"The (not so) immortal strand hypothesis","volume":"14","author":"C Tomasetti","year":"2015","journal-title":"Stem Cell Research"},{"issue":"1","key":"pcbi.1010677.ref024","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-14844-6","article-title":"Measuring single cell divisions in human tissues from multi-region sequencing data","volume":"11","author":"B Werner","year":"2020","journal-title":"Nature Communications"},{"issue":"43","key":"pcbi.1010677.ref025","doi-asserted-by":"crossref","first-page":"18545","DOI":"10.1073\/pnas.1010978107","article-title":"Accumulation of driver and passenger mutations during tumor progression","volume":"107","author":"I Bozic","year":"2010","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"7","key":"pcbi.1010677.ref026","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/ng.3891","article-title":"Between-region genetic divergence reflects the mode and tempo of tumor evolution","volume":"49","author":"R Sun","year":"2017","journal-title":"Nature Genetics"},{"issue":"7762","key":"pcbi.1010677.ref027","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"},{"issue":"1","key":"pcbi.1010677.ref028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-14407-9","article-title":"Estimating growth patterns and driver effects in tumor evolution from individual samples","volume":"11","author":"L Salichos","year":"2020","journal-title":"Nature Communications"},{"key":"pcbi.1010677.ref029","article-title":"Spatial structure governs the mode of tumour evolution","author":"R Noble","year":"2021","journal-title":"Nature Ecology & Evolution"},{"issue":"7","key":"pcbi.1010677.ref030","doi-asserted-by":"crossref","first-page":"e1007243","DOI":"10.1371\/journal.pcbi.1007243","article-title":"Spatially constrained tumour growth affects the patterns of clonal selection and neutral drift in cancer genomic data","volume":"15","author":"K Chkhaidze","year":"2019","journal-title":"PLOS Computational Biology"},{"key":"pcbi.1010677.ref031","article-title":"Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study","author":"X Fu","year":"2021","journal-title":"Nature Ecology & Evolution"},{"issue":"6","key":"pcbi.1010677.ref032","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s41588-018-0128-6","article-title":"Quantification of subclonal selection in cancer from bulk sequencing data","volume":"50","author":"MJ Williams","year":"2018","journal-title":"Nature Genetics"},{"issue":"50","key":"pcbi.1010677.ref033","doi-asserted-by":"crossref","first-page":"eabc4308","DOI":"10.1126\/sciadv.abc4308","article-title":"A mathematical model of ctDNA shedding predicts tumor detection size","volume":"6","author":"S Avanzini","year":"2020","journal-title":"Science Advances"},{"key":"pcbi.1010677.ref034","doi-asserted-by":"crossref","first-page":"e00747","DOI":"10.7554\/eLife.00747","article-title":"Evolutionary dynamics of cancer in response to targeted combination therapy","volume":"2","author":"I Bozic","year":"2013","journal-title":"eLife"},{"issue":"1","key":"pcbi.1010677.ref035","first-page":"129","article-title":"Statistical Inference for the Evolutionary History of Cancer Genomes","volume":"35","author":"KN Dinh","year":"2020","journal-title":"Statistical Science"},{"issue":"2","key":"pcbi.1010677.ref036","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1073\/pnas.1914589117","article-title":"Revisiting the tumorigenesis timeline with a data-driven generative model","volume":"117","author":"K Lahouel","year":"2020","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"6","key":"pcbi.1010677.ref037","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s43018-020-0079-6","article-title":"Delineating the evolutionary dynamics of cancer from theory to reality","volume":"1","author":"I Bozic","year":"2020","journal-title":"Nature Cancer"},{"key":"pcbi.1010677.ref038","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-16065-8","volume-title":"Branching Process Models of Cancer. Mathematical Biosciences Institute Lecture Series","author":"R Durrett","year":"2015"},{"issue":"A","key":"pcbi.1010677.ref039","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1017\/apr.2018.84","article-title":"The linear birth-death process: an inferential retrospective","volume":"50","author":"S Tavar\u00e9","year":"2018","journal-title":"Advances in Applied Probability"},{"issue":"28","key":"pcbi.1010677.ref040","doi-asserted-by":"crossref","first-page":"14129","DOI":"10.1073\/pnas.1819408116","article-title":"Consecutive seeding and transfer of genetic diversity in metastasis","volume":"116","author":"A Heyde","year":"2019","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"3","key":"pcbi.1010677.ref041","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.cels.2015.08.015","article-title":"Optimizing Cancer Genome Sequencing and Analysis","volume":"1","author":"M Griffith","year":"2015","journal-title":"Cell Systems"},{"issue":"6","key":"pcbi.1010677.ref042","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1158\/2159-8290.CD-13-1014","article-title":"Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA","volume":"4","author":"DA Haber","year":"2014","journal-title":"Cancer Discovery"},{"key":"pcbi.1010677.ref043","article-title":"Comprehensive analysis of tumour initiation, spatial and temporal progression under multiple lines of treatment","author":"I Leshchiner","year":"2018","journal-title":"Bioinformatics"},{"issue":"6","key":"pcbi.1010677.ref044","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.cels.2019.05.010","article-title":"CALDER: Inferring Phylogenetic Trees from Longitudinal Tumor Samples","volume":"8","author":"MA Myers","year":"2019","journal-title":"Cell Systems"},{"issue":"25","key":"pcbi.1010677.ref045","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1182\/blood-2017-09-806398","article-title":"iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL","volume":"131","author":"M Hallek","year":"2018","journal-title":"Blood"},{"issue":"5","key":"pcbi.1010677.ref046","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1093\/labmed\/lmaa119","article-title":"Smudge Cells in Chronic Lymphocytic Leukemia: Pathophysiology, Laboratory Considerations, and Clinical Significance","volume":"52","author":"SM Marionneaux","year":"2021","journal-title":"Laboratory Medicine"},{"issue":"2","key":"pcbi.1010677.ref047","doi-asserted-by":"crossref","first-page":"e1004731","DOI":"10.1371\/journal.pcbi.1004731","article-title":"Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution","volume":"12","author":"I Bozic","year":"2016","journal-title":"PLOS Computational Biology"},{"issue":"1","key":"pcbi.1010677.ref048","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/s41467-019-09026-y","article-title":"The use of technical replication for detection of low-level somatic mutations in next-generation sequencing","volume":"10","author":"J Kim","year":"2019","journal-title":"Nature Communications"},{"issue":"7","key":"pcbi.1010677.ref049","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/s41551-021-00713-0","article-title":"Selective multiplexed enrichment for the detection and quantitation of low-fraction DNA variants via low-depth sequencing","volume":"5","author":"P Song","year":"2021","journal-title":"Nature Biomedical Engineering"},{"issue":"7913","key":"pcbi.1010677.ref050","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41586-022-04785-z","article-title":"The longitudinal dynamics and natural history of clonal haematopoiesis","volume":"606","author":"MA Fabre","year":"2022","journal-title":"Nature"},{"issue":"7624","key":"pcbi.1010677.ref051","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/nature19768","article-title":"Tissue-specific mutation accumulation in human adult stem cells during life","volume":"538","author":"F Blokzijl","year":"2016","journal-title":"Nature"},{"issue":"7913","key":"pcbi.1010677.ref052","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41586-022-04786-y","article-title":"Clonal dynamics of haematopoiesis across the human lifespan","volume":"606","author":"E Mitchell","year":"2022","journal-title":"Nature"},{"issue":"19","key":"pcbi.1010677.ref053","doi-asserted-by":"crossref","first-page":"9501","DOI":"10.1073\/pnas.1901695116","article-title":"In silico learning of tumor evolution through mutational time series","volume":"116","author":"N Auslander","year":"2019","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"7859","key":"pcbi.1010677.ref054","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/s41586-021-03477-4","article-title":"Somatic mutation landscapes at single-molecule resolution","volume":"593","author":"F Abascal","year":"2021","journal-title":"Nature"},{"issue":"7793","key":"pcbi.1010677.ref055","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"PCAWG Mutational Signatures Working Group, PCAWG Consortium","year":"2020","journal-title":"Nature"},{"key":"pcbi.1010677.ref056","article-title":"Evolving copy number gains promote tumor expansion and bolster mutational diversification","author":"Z Wang","year":"2022","journal-title":"Genomics"},{"issue":"4","key":"pcbi.1010677.ref057","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/(SICI)1096-9098(199708)65:4<284::AID-JSO11>3.0.CO;2-2","article-title":"On the growth rates of human malignant tumors: implications for medical decision making","volume":"65","author":"S Friberg","year":"1997","journal-title":"Journal of Surgical Oncology"},{"issue":"10","key":"pcbi.1010677.ref058","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.tree.2013.05.020","article-title":"Tumor growth dynamics: insights into evolutionary processes","volume":"28","author":"IA Rodriguez-Brenes","year":"2013","journal-title":"Trends in Ecology & Evolution"},{"issue":"10","key":"pcbi.1010677.ref059","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1007\/s11538-015-0110-8","article-title":"Estimating Tumor Growth Rates In Vivo","volume":"77","author":"A Talkington","year":"2015","journal-title":"Bulletin of Mathematical Biology"},{"issue":"24 Pt 1","key":"pcbi.1010677.ref060","first-page":"7067","article-title":"A Gompertzian model of human breast cancer growth","volume":"48","author":"L Norton","year":"1988","journal-title":"Cancer Research"},{"issue":"6","key":"pcbi.1010677.ref061","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1002\/1097-0142(19930315)71:6<2013::AID-CNCR2820710615>3.0.CO;2-V","article-title":"Decelerating growth and human breast cancer","volume":"71","author":"JA Spratt","year":"1993","journal-title":"Cancer"},{"issue":"8","key":"pcbi.1010677.ref062","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1158\/0008-5472.CAN-12-4355","article-title":"The Model Muddle: In Search of Tumor Growth Laws","volume":"73","author":"P Gerlee","year":"2013","journal-title":"Cancer Research"},{"issue":"2","key":"pcbi.1010677.ref063","doi-asserted-by":"crossref","first-page":"e1007178","DOI":"10.1371\/journal.pcbi.1007178","article-title":"Population modeling of tumor growth curves and the reduced Gompertz model improve prediction of the age of experimental tumors","volume":"16","author":"C Vaghi","year":"2020","journal-title":"PLOS Computational Biology"},{"issue":"1","key":"pcbi.1010677.ref064","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/BF00391826","article-title":"Estimation of liver tumor volume using different formulas?An experimental study in rats","volume":"105","author":"G Carlsson","year":"1983","journal-title":"Journal of Cancer Research and Clinical Oncology"},{"issue":"1","key":"pcbi.1010677.ref065","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1038\/s41467-021-22123-1","article-title":"Normal tissue architecture determines the evolutionary course of cancer","volume":"12","author":"J West","year":"2021","journal-title":"Nature Communications"},{"issue":"7520","key":"pcbi.1010677.ref066","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nature13556","article-title":"Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity","volume":"514","author":"A Marusyk","year":"2014","journal-title":"Nature"},{"issue":"6","key":"pcbi.1010677.ref067","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.cell.2019.02.012","article-title":"Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis","volume":"176","author":"M Petljak","year":"2019","journal-title":"Cell"},{"issue":"25","key":"pcbi.1010677.ref068","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":"The Journal of Physical Chemistry"},{"issue":"9","key":"pcbi.1010677.ref069","doi-asserted-by":"crossref","first-page":"e1007368","DOI":"10.1371\/journal.pcbi.1007368","article-title":"On measuring selection in cancer from subclonal mutation frequencies","volume":"15","author":"I Bozic","year":"2019","journal-title":"PLOS Computational Biology"},{"key":"pcbi.1010677.ref070","volume-title":"Rodak\u2019s hematology: clinical principles and applications","author":"EM Keohane","year":"2016","edition":"5"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1010677","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1010677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T18:43:23Z","timestamp":1668624203000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1010677"}},"subtitle":[],"editor":[{"given":"Jasmine","family":"Foo","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2022,11,4]]},"references-count":70,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1010677","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1010677","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,4]]}}}