{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:33:13Z","timestamp":1773275593218,"version":"3.50.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":480,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Phylogenetic algorithms have begun to see widespread use in cancer research to reconstruct processes of evolution in tumor progression. Developing reliable phylogenies for tumor data requires quantitative models of cancer evolution that include the unusual genetic mechanisms by which tumors evolve, such as chromosome abnormalities, and allow for heterogeneity between tumor types and individual patients. Previous work on inferring phylogenies of single tumors by copy number evolution assumed models of uniform rates of genomic gain and loss across different genomic sites and scales, a substantial oversimplification necessitated by a lack of algorithms and quantitative parameters for fitting to more realistic tumor evolution models.<\/jats:p><jats:p>Results: We propose a framework for inferring models of tumor progression from single-cell gene copy number data, including variable rates for different gain and loss events. We propose a new algorithm for identification of most parsimonious combinations of single gene and single chromosome events. We extend it via dynamic programming to include genome duplications. We implement an expectation maximization (EM)-like method to estimate mutation-specific and tumor-specific event rates concurrently with tree reconstruction. Application of our algorithms to real cervical cancer data identifies key genomic events in disease progression consistent with prior literature. Classification experiments on cervical and tongue cancer datasets lead to improved prediction accuracy for the metastasis of primary cervical cancers and for tongue cancer survival.<\/jats:p><jats:p>Availability and implementation: Our software (FISHtrees) and two datasets are available at ftp:\/\/ftp.ncbi.nlm.nih.gov\/pub\/FISHtrees.<\/jats:p><jats:p>Contact: \u00a0russells@andrew.cmu.edu<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv233","type":"journal-article","created":{"date-parts":[[2015,6,13]],"date-time":"2015-06-13T17:12:36Z","timestamp":1434215556000},"page":"i258-i267","source":"Crossref","is-referenced-by-count":29,"title":["Inferring models of multiscale copy number evolution for single-tumor phylogenetics"],"prefix":"10.1093","volume":"31","author":[{"given":"Salim Akhter","family":"Chowdhury","sequence":"first","affiliation":[{"name":"1 Joint Carnegie Mellon\/University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA, 2Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA, 3Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, USA, 4Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD, USA and 5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"},{"name":"1 Joint Carnegie Mellon\/University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA, 2Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA, 3Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, USA, 4Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD, USA and 5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"}]},{"given":"E. Michael","family":"Gertz","sequence":"additional","affiliation":[{"name":"1 Joint Carnegie Mellon\/University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA, 2Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA, 3Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, USA, 4Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD, USA and 5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"}]},{"given":"Darawalee","family":"Wangsa","sequence":"additional","affiliation":[{"name":"1 Joint Carnegie Mellon\/University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA, 2Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA, 3Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, USA, 4Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD, USA and 5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"}]},{"given":"Kerstin","family":"Heselmeyer-Haddad","sequence":"additional","affiliation":[{"name":"1 Joint Carnegie Mellon\/University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA, 2Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA, 3Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, USA, 4Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD, USA and 5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"}]},{"given":"Thomas","family":"Ried","sequence":"additional","affiliation":[{"name":"1 Joint Carnegie Mellon\/University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA, 2Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA, 3Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, USA, 4Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD, USA and 5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"}]},{"given":"Alejandro A.","family":"Sch\u00e4ffer","sequence":"additional","affiliation":[{"name":"1 Joint Carnegie Mellon\/University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA, 2Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA, 3Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, USA, 4Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD, USA and 5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"}]},{"given":"Russell","family":"Schwartz","sequence":"additional","affiliation":[{"name":"1 Joint Carnegie Mellon\/University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA, 2Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA, 3Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, USA, 4Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD, USA and 5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"},{"name":"1 Joint Carnegie Mellon\/University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA, 2Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA, 3Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, USA, 4Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD, USA and 5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"}]}],"member":"286","published-online":{"date-parts":[[2015,6,10]]},"reference":[{"key":"2023020115425545000_btv233-B1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/oxfordjournals.molbev.a026036","article-title":"Median-joining networks for inferring intraspecific phylogenies","volume":"16","author":"Bandelt","year":"1999","journal-title":"Mol. Biol. Evol."},{"key":"2023020115425545000_btv233-B2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1146\/annurev-ecolsys-102209-144621","article-title":"Approximate Bayesian computation in evolution and ecology","volume":"41","author":"Beaumont","year":"2010","journal-title":"Annu. Rev. Ecol. Evol. Syst."},{"key":"2023020115425545000_btv233-B3","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":"2015","journal-title":"Syst. Biol."},{"key":"2023020115425545000_btv233-B4","doi-asserted-by":"crossref","first-page":"i189","DOI":"10.1093\/bioinformatics\/btt205","article-title":"Phylogenetic analysis of multiprobe fluorescence in situ hybridization data from tumor cell populations","volume":"29","author":"Chowdhury","year":"2013","journal-title":"Bioinformatics"},{"key":"2023020115425545000_btv233-B5","doi-asserted-by":"crossref","first-page":"e1003740","DOI":"10.1371\/journal.pcbi.1003740","article-title":"Algorithms to model single gene, single chromosome, and whole genome copy number changes jointly in tumor phylogenetics","volume":"10","author":"Chowdhury","year":"2014","journal-title":"PLoS Comp. Biol."},{"key":"2023020115425545000_btv233-B6","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1093\/bioinformatics\/btq315","article-title":"Count: evolutionary analysis of phylogenetic profiles with parsimony and likelihood","volume":"26","author":"Cs\u0171r\u00f6s","year":"2010","journal-title":"Bioinformatics"},{"key":"2023020115425545000_btv233-B7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.2517-6161.1977.tb01600.x","article-title":"Maximum likelihood from incomplete data via the EM algorithm","volume":"39","author":"Dempster","year":"1977","journal-title":"J. R. Stat. Soc. B"},{"key":"2023020115425545000_btv233-B8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1089\/cmb.1999.6.37","article-title":"Inferring tree models of oncogenesis from comparative genomic hybridization data","volume":"6","author":"Desper","year":"1999","journal-title":"J. Comput. Biol."},{"key":"2023020115425545000_btv233-B9","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1089\/10665270050514936","article-title":"Distance-based reconstruction of tree models for oncogenesis","volume":"7","author":"Desper","year":"2000","journal-title":"J. Comput. Biol."},{"key":"2023020115425545000_btv233-B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.biochem.76.061705.090740","article-title":"Molecular mechanisms of antibody somatic hypermutation","volume":"76","author":"Di Noia","year":"2007","journal-title":"Annu. Rev. Biochem."},{"key":"2023020115425545000_btv233-B11","volume-title":"Inferring Phylogenies","author":"Felsenstein","year":"2004"},{"key":"2023020115425545000_btv233-B12","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/bjc.2012.581","article-title":"Cancer heterogeneity: implications for targeted therapeutics","volume":"108","author":"Fisher","year":"2013","journal-title":"Br. J. Cancer"},{"key":"2023020115425545000_btv233-B13","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1101\/gr.118414.110","article-title":"Estimation of rearrangement phylogeny for cancer genomes","volume":"22","author":"Greenman","year":"2010","journal-title":"Genome Res."},{"key":"2023020115425545000_btv233-B14","first-page":"4855","article-title":"Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis","volume":"54","author":"Greenblatt","year":"1994","journal-title":"Cancer Res."},{"key":"2023020115425545000_btv233-B15","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/S1097-2765(02)00742-6","article-title":"RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators","volume":"10","author":"Harris","year":"2002","journal-title":"Mol. Cell"},{"key":"2023020115425545000_btv233-B16","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s10555-013-9427-7","article-title":"Chromosome instability (CIN): what it is and why it is crucial to cancer evolution","volume":"32","author":"Heng","year":"2013","journal-title":"Cancer Metastasis Rev."},{"key":"2023020115425545000_btv233-B17","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.ajpath.2012.07.012","article-title":"Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity, yet conserved genomic imbalances and gain of MYC during progression","volume":"181","author":"Heselmeyer-Haddad","year":"2012","journal-title":"Am. J. Pathol."},{"key":"2023020115425545000_btv233-B18","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1089\/cmb.2006.13.853","article-title":"New probabilistic network models and algorithms for oncogenesis","volume":"13","author":"Hjelm","year":"2006","journal-title":"J. Comput. Biol."},{"key":"2023020115425545000_btv233-B19","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/net.3230010305","article-title":"A simple derivation of edmonds\u2019 algorithm for optimum branchings","volume":"1","author":"Karp","year":"1971","journal-title":"Networks"},{"key":"2023020115425545000_btv233-B20","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1093\/bioinformatics\/btp365","article-title":"Inferring progression models for CGH data","volume":"25","author":"Liu","year":"2009","journal-title":"Bioinformatics"},{"key":"2023020115425545000_btv233-B21","first-page":"3075","article-title":"Mutator phenotype may be required for multistage carcinogenesis","volume":"51","author":"Loeb","year":"1991","journal-title":"Cancer Res."},{"key":"2023020115425545000_btv233-B22","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1158\/2159-8290.CD-11-0325","article-title":"Evolutionary pathways in BRCA1-associated breast tumors","volume":"2","author":"Martins","year":"2012","journal-title":"Cancer Discov."},{"key":"2023020115425545000_btv233-B23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.bbcan.2009.11.002","article-title":"Tumor heterogeneity: causes and consequences","volume":"1805","author":"Marusyk","year":"2010","journal-title":"Biochim. Biophys. Acta (BBA) Rev. Cancer"},{"key":"2023020115425545000_btv233-B24","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature09807","article-title":"Tumour evolution inferred by single-cell sequencing","volume":"472","author":"Navin","year":"2011","journal-title":"Nature"},{"key":"2023020115425545000_btv233-B25","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1198\/016214502388618726","article-title":"Discovering combinations of genomic aberrations associated with cancer","volume":"97","author":"Newton","year":"2002","journal-title":"J. Am. Stat. Assoc."},{"key":"2023020115425545000_btv233-B26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1126\/science.959840","article-title":"The clonal evolution of tumor cell populations","volume":"194","author":"Nowell","year":"1976","journal-title":"Science"},{"key":"2023020115425545000_btv233-B27","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1142\/S021972000700259X","article-title":"Reconstructing tumor phylogenies from heterogeneous single-cell data","volume":"5","author":"Pennington","year":"2007","journal-title":"J. Bioinform. Comput. Biol."},{"key":"2023020115425545000_btv233-B28","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ccr.2008.02.020","article-title":"Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype","volume":"13","author":"Petrova","year":"2008","journal-title":"Cancer Cell"},{"key":"2023020115425545000_btv233-B29","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1093\/bioinformatics\/btt546","article-title":"Methods and challenges in timing chromosomal abnormalities within cancer samples","volume":"29","author":"Purdom","year":"2013","journal-title":"Bioinformatics"},{"key":"2023020115425545000_btv233-B30","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.ccr.2011.11.005","article-title":"Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma","volume":"20","author":"Snuderl","year":"2011","journal-title":"Cancer Cell"},{"key":"2023020115425545000_btv233-B31","doi-asserted-by":"crossref","first-page":"629","DOI":"10.3109\/00313025.2010.522174","article-title":"Tumour expression of lymphangiogenic growth factors but not lymphatic density is implicated in human cervical progression","volume":"42","author":"Sotiropoulou","year":"2010","journal-title":"Pathology"},{"key":"2023020115425545000_btv233-B32","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1158\/1940-6207.CAPR-10-0374","article-title":"Accurate reconstruction of the temporal order of mutations in neoplastic progression","volume":"4","author":"Sprouffske","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"2023020115425545000_btv233-B33","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1073\/pnas.1114033109","article-title":"Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response","volume":"109","author":"Szerlip","year":"2012","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2023020115425545000_btv233-B34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/net.3230070103","article-title":"Finding optimum branchings","volume":"7","author":"Tarjan","year":"1977","journal-title":"Networks"},{"key":"2023020115425545000_btv233-B35","doi-asserted-by":"crossref","first-page":"e15661","DOI":"10.1371\/journal.pone.0015661","article-title":"Somatic mutation profiles of MSI and MSS colorectal cancer identified by whole exome next generation sequencing and bioinformatics analysis","volume":"5","author":"Timmermann","year":"2010","journal-title":"PLoS One"},{"key":"2023020115425545000_btv233-B36","first-page":"1601","article-title":"Clonal cytogenetic progression within intratumorally heterogeneous meningiomas predicts tumor recurrence","volume":"39","author":"Urbschat","year":"2011","journal-title":"Int. J. Oncol."},{"key":"2023020115425545000_btv233-B37","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nature13600","article-title":"Clonal evolution in breast cancer revealed by single nucleus genome sequencing","volume":"512","author":"Wang","year":"2014","journal-title":"Nature"},{"key":"2023020115425545000_btv233-B38","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.2353\/ajpath.2009.090289","article-title":"Fluorescence in situ hybridization markers for prediction of cervical lymph node metastases","volume":"175","author":"Wangsa","year":"2009","journal-title":"Am. J. Pathol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/12\/i258\/49014042\/bioinformatics_31_12_i258.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/12\/i258\/49014042\/bioinformatics_31_12_i258.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T14:00:34Z","timestamp":1717941634000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/31\/12\/i258\/215450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,10]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,6,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btv233","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,6,15]]},"published":{"date-parts":[[2015,6,10]]}}}