{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T16:02:52Z","timestamp":1772726572151,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T00:00:00Z","timestamp":1529452800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["LM012487"],"award-info":[{"award-number":["LM012487"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["LM012758"],"award-info":[{"award-number":["LM012758"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Analyses of data generated from bulk sequencing of tumors have revealed extensive genomic heterogeneity within patients. Many computational methods have been developed to enable the inference of genotypes of tumor cell populations (clones) from bulk sequencing data. However, the relative and absolute accuracy of available computational methods in estimating clone counts and clone genotypes is not yet known.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We have assessed the performance of nine methods, including eight previously-published and one new method (CloneFinder), by analyzing computer simulated datasets. CloneFinder, LICHeE, CITUP and cloneHD inferred clone genotypes with low error (&amp;lt;5% per clone) for a majority of datasets in which the tumor samples contained evolutionarily-related clones. Computational methods did not perform well for datasets in which tumor samples contained mixtures of clones from different clonal lineages. Generally, the number of clones was underestimated by cloneHD and overestimated by PhyloWGS, and BayClone2, Canopy and Clomial required prior information regarding the number of clones. AncesTree and Canopy did not produce results for a large number of datasets. Overall, the deconvolution of clone genotypes from single nucleotide variant (SNV) frequency differences among tumor samples remains challenging, so there is a need to develop more accurate computational methods and robust software for clone genotype inference.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>CloneFinder is implemented in Python and is available from https:\/\/github.com\/gstecher\/CloneFinderAPI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty469","type":"journal-article","created":{"date-parts":[[2018,6,12]],"date-time":"2018-06-12T15:10:33Z","timestamp":1528816233000},"page":"4017-4026","source":"Crossref","is-referenced-by-count":30,"title":["Predicting clone genotypes from tumor bulk sequencing of multiple samples"],"prefix":"10.1093","volume":"34","author":[{"given":"Sayaka","family":"Miura","sequence":"first","affiliation":[{"name":"Institute for Genomics and Evolutionary Medicine"},{"name":"Department of Biology, Temple University, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Gomez","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Evolutionary Medicine"},{"name":"Department of Biology, Temple University, Philadelphia, PA, USA"},{"name":"College of Physicians and Surgeons, Columbia University, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Murillo","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Evolutionary Medicine"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise A","family":"Huuki","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Evolutionary Medicine"},{"name":"Department of Biology, Temple University, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"Vu","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Evolutionary Medicine"},{"name":"Department of Biology, Temple University, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Buturla","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Evolutionary Medicine"},{"name":"Department of Biology, Temple University, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudhir","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Evolutionary Medicine"},{"name":"Department of Biology, Temple University, Philadelphia, PA, USA"},{"name":"Center for Excellence in Genome Medicine and Research, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,6,19]]},"reference":[{"key":"2023012712312469400_bty469-B1","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.trecan.2017.06.004","article-title":"Multiregional tumor trees are not phylogenies","volume":"3","author":"Alves","year":"2017","journal-title":"Trends Cancer"},{"key":"2023012712312469400_bty469-B2","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/sysbio\/syu081","article-title":"Cancer evolution: mathematical models and computational inference","volume":"64","author":"Beerenwinkel","year":"2014","journal-title":"Syst. Biol."},{"key":"2023012712312469400_bty469-B3","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nature20805","article-title":"Integrated genomic characterization of oesophageal carcinoma","volume":"541","author":"Cancer Genome Atlas Research Network et\u00a0al.","year":"2017","journal-title":"Nature"},{"key":"2023012712312469400_bty469-B4","first-page":"151","article-title":"Tumor evolution: linear, branching, neutral or punctuated? Biochim","volume":"1867","author":"Davis","year":"2017","journal-title":"Biophys. Acta"},{"key":"2023012712312469400_bty469-B5","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1126\/science.1253462","article-title":"Spatial and temporal diversity in genomic instability processes defines lung cancer evolution","volume":"346","author":"de Bruin","year":"2014","journal-title":"Science"},{"key":"2023012712312469400_bty469-B6","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13059-015-0602-8","article-title":"PhyloWGS: reconstructing subclonal composition and evolution from whole-genome sequencing of tumors","volume":"16","author":"Deshwar","year":"2015","journal-title":"Genome Biol."},{"key":"2023012712312469400_bty469-B7","doi-asserted-by":"crossref","first-page":"i62","DOI":"10.1093\/bioinformatics\/btv261","article-title":"Reconstruction of clonal trees and tumor composition from multi-sample sequencing data","volume":"31","author":"El-Kebir","year":"2015","journal-title":"Bioinformatics"},{"key":"2023012712312469400_bty469-B8","doi-asserted-by":"crossref","first-page":"13467","DOI":"10.1038\/s41598-017-13338-8","article-title":"Engineered in-vitro cell line mixtures and robust evaluation of computational methods for clonal decomposition and longitudinal dynamics in cancer","volume":"7","author":"Farahani","year":"2017","journal-title":"Sci. Rep."},{"key":"2023012712312469400_bty469-B41","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1016\/j.celrep.2014.04.055","article-title":"High-definition reconstruction of clonal composition in cancer","volume":"7","author":"Fischer","year":"2014","journal-title":"Cell Rep"},{"key":"2023012712312469400_bty469-B9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrg.2015.16","article-title":"Single-cell genome sequencing: current state of the science","volume":"17","author":"Gawad","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"2023012712312469400_bty469-B10","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor heterogeneity and branched evolution revealed by multiregion sequencing","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2023012712312469400_bty469-B11","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/ng.2891","article-title":"Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing","volume":"46","author":"Gerlinger","year":"2014","journal-title":"Nat. Genet."},{"key":"2023012712312469400_bty469-B12","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nature14347","article-title":"The evolutionary history of lethal metastatic prostate cancer","volume":"520","author":"Gundem","year":"2015","journal-title":"Nature"},{"key":"2023012712312469400_bty469-B13","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nrg3729","article-title":"Mechanisms underlying mutational signatures in human cancers","volume":"15","author":"Helleday","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"2023012712312469400_bty469-B14","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1158\/0008-5472.CAN-15-1889","article-title":"Inferring the origin of metastases from cancer phylogenies","volume":"75","author":"Hong","year":"2015","journal-title":"Cancer Res"},{"key":"2023012712312469400_bty469-B15","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1002\/ijc.29031","article-title":"Evolutionary mechanism unifies the hallmarks of cancer","volume":"136","author":"Horne","year":"2015","journal-title":"Int. J. Cancer"},{"key":"2023012712312469400_bty469-B16","first-page":"109","article-title":"A population genetics perspective on the determinants of intra-tumor heterogeneity","volume":"1867","author":"Hu","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"2023012712312469400_bty469-B17","doi-asserted-by":"crossref","first-page":"E5528","DOI":"10.1073\/pnas.1522203113","article-title":"Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing","volume":"113","author":"Jiang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023012712312469400_bty469-B18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1471-2105-15-35","article-title":"Inferring clonal evolution of tumors from single nucleotide somatic mutations","volume":"15","author":"Jiao","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"2023012712312469400_bty469-B19","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1525\/9780520411586-036","article-title":"Nonlinear programming","volume-title":"Proceedings of the Second Berkeley Symposium on Mathematical Statistics and Probability, 1950","author":"Kuhn","year":"1951"},{"key":"2023012712312469400_bty469-B20","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.cell.2013.01.019","article-title":"Evolution and impact of subclonal mutations in chronic lymphocytic leukemia","volume":"152","author":"Landau","year":"2013","journal-title":"Cell"},{"key":"2023012712312469400_bty469-B21","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1158\/1078-0432.CCR-16-0234","article-title":"How subclonal modeling is changing the metastatic paradigm","volume":"23","author":"Macintyre","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"2023012712312469400_bty469-B22","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1093\/bioinformatics\/btv003","article-title":"Clonality inference in multiple tumor samples using phylogeny","volume":"31","author":"Malikic","year":"2015","journal-title":"Bioinformatics"},{"key":"2023012712312469400_bty469-B23","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/ng.3573","article-title":"Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer","volume":"48","author":"McPherson","year":"2016","journal-title":"Nat. Genet."},{"key":"2023012712312469400_bty469-B24","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1101\/gr.191098.115","article-title":"The first five years of single-cell cancer genomics and beyond","volume":"25","author":"Navin","year":"2015","journal-title":"Genome Res."},{"key":"2023012712312469400_bty469-B25","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195135848.001.0001","volume-title":"Molecular Evolution and Phylogenetics","author":"Nei","year":"2000"},{"key":"2023012712312469400_bty469-B26","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.cell.2012.04.023","article-title":"The life history of 21 breast cancers","volume":"149","author":"Nik-Zainal","year":"2012","journal-title":"Cell"},{"key":"2023012712312469400_bty469-B27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1089\/biores.2014.0035","article-title":"Autophagy in cancer stem cells: a potential link between chemoresistance, recurrence, and metastasis","volume":"4","author":"Ojha","year":"2015","journal-title":"Biores. Open Access"},{"key":"2023012712312469400_bty469-B28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13059-015-0647-8","article-title":"Fast and scalable inference of multi-sample cancer lineages","volume":"16","author":"Popic","year":"2015","journal-title":"Genome Biol."},{"key":"2023012712312469400_bty469-B29","doi-asserted-by":"crossref","first-page":"14114","DOI":"10.1038\/ncomms14114","article-title":"Reconstructing metastatic seeding patterns of human cancers","volume":"8","author":"Reiter","year":"2017","journal-title":"Nat. Commun."},{"key":"2023012712312469400_bty469-B30","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/ng.3357","article-title":"Whole-genome sequencing provides new insights into the clonal architecture of Barrett\u2019s esophagus and esophageal adenocarcinoma","volume":"47","author":"Ross-Innes","year":"2015","journal-title":"Nat. Genet."},{"key":"2023012712312469400_bty469-B31","doi-asserted-by":"crossref","first-page":"4191","DOI":"10.1182\/blood-2012-05-433540","article-title":"Monitoring chronic lymphocytic leukemia progression by whole genome sequencing reveals heterogeneous clonal evolution patterns","volume":"120","author":"Schuh","year":"2012","journal-title":"Blood"},{"key":"2023012712312469400_bty469-B32","first-page":"478","article-title":"Bayclone: Bayesian nonparametric inference of tumor subclones using NGS data","volume":"467","author":"Sengupta","year":"2015","journal-title":"Pac. Symp. Biocomput."},{"key":"2023012712312469400_bty469-B33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/ng.3214","article-title":"A Big Bang model of human colorectal tumor growth","volume":"47","author":"Sottoriva","year":"2015","journal-title":"Nat. Genet."},{"key":"2023012712312469400_bty469-B34","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/ng.3343","article-title":"Paired exome analysis of Barrett\u2019s esophagus and adenocarcinoma","volume":"47","author":"Stachler","year":"2015","journal-title":"Nat. Genet."},{"key":"2023012712312469400_bty469-B35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2015.04.022","article-title":"Recent advances and current issues in single-cell sequencing of tumors","volume":"365","author":"Sun","year":"2015","journal-title":"Cancer Lett."},{"key":"2023012712312469400_bty469-B36","first-page":"264","article-title":"Inferring mutational timing and reconstructing tumour evolutionary histories","volume":"1855","author":"Turajlic","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"2023012712312469400_bty469-B37","doi-asserted-by":"crossref","first-page":"e1005778","DOI":"10.1371\/journal.pgen.1005778","article-title":"Integrated multiregional analysis proposing a new model of colorectal cancer evolution","volume":"12","author":"Uchi","year":"2016","journal-title":"PLoS Genet."},{"key":"2023012712312469400_bty469-B38","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fgene.2017.00083","article-title":"Computational methods for characterizing cancer mutational heterogeneity","volume":"8","author":"Vandin","year":"2017","journal-title":"Front. Genet."},{"key":"2023012712312469400_bty469-B39","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/genetics\/141.4.1641","article-title":"A new method of inference of ancestral nucleotide and amino acid sequences","volume":"141","author":"Yang","year":"1995","journal-title":"Genetics"},{"key":"2023012712312469400_bty469-B40","doi-asserted-by":"crossref","first-page":"e1003703","DOI":"10.1371\/journal.pcbi.1003703","article-title":"Inferring clonal composition from multiple sections of a breast cancer","volume":"10","author":"Zare","year":"2014","journal-title":"PLoS Comput. Biol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/34\/23\/4017\/48921182\/bioinformatics_34_23_4017.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/34\/23\/4017\/48921182\/bioinformatics_34_23_4017.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T08:38:06Z","timestamp":1720341486000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/34\/23\/4017\/5040314"}},"subtitle":[],"editor":[{"given":"John","family":"Hancock","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,6,19]]},"references-count":41,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2018,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bty469","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/341180","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,12,1]]},"published":{"date-parts":[[2018,6,19]]}}}