{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:23:34Z","timestamp":1770359014868,"version":"3.49.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Weill Cornell Medicine"},{"name":"Tri-Institutional Training Program in Computational Biology and Medicine","award":["1T32GM083937"],"award-info":[{"award-number":["1T32GM083937"]}]},{"name":"US National Science Foundation (NSF) Award","award":["IIS-1840275"],"award-info":[{"award-number":["IIS-1840275"]}]},{"name":"US National Institute of Health","award":["R01CA183904"],"award-info":[{"award-number":["R01CA183904"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>We propose Meltos, a novel computational framework to address the challenging problem of building tumor phylogeny trees using somatic structural variants (SVs) among multiple samples. Meltos leverages the tumor phylogeny tree built on somatic single nucleotide variants (SNVs) to identify high confidence SVs and produce a comprehensive tumor lineage tree, using a novel optimization formulation. While we do not assume the evolutionary progression of SVs is necessarily the same as SNVs, we show that a tumor phylogeny tree using high-quality somatic SNVs can act as a guide for calling and assigning somatic SVs on a tree. Meltos utilizes multiple genomic read signals for potential SV breakpoints in whole genome sequencing data and proposes a probabilistic formulation for estimating variant allele fractions (VAFs) of SV events.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In order to assess the ability of Meltos to correctly refine SNV trees with SV information, we tested Meltos on two simulated datasets with five genomes in both. We also assessed Meltos on two real cancer datasets. We tested Meltos on multiple samples from a liposarcoma tumor and on a multi-sample breast cancer data (Yates et al., 2015), where the authors provide validated structural variation events together with deep, targeted sequencing for a collection of somatic SNVs. We show Meltos has the ability to place high confidence validated SV calls on a refined tumor phylogeny tree. We also showed the flexibility of Meltos to either estimate VAFs directly from genomic data or to use copy number corrected estimates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Meltos is available at https:\/\/github.com\/ih-lab\/Meltos.<\/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\/btz737","type":"journal-article","created":{"date-parts":[[2019,9,26]],"date-time":"2019-09-26T11:28:48Z","timestamp":1569497328000},"page":"1082-1090","source":"Crossref","is-referenced-by-count":13,"title":["Meltos: multi-sample tumor phylogeny reconstruction for structural variants"],"prefix":"10.1093","volume":"36","author":[{"given":"Camir","family":"Ricketts","sequence":"first","affiliation":[{"name":"Tri-Institutional Training Program in Computational Biology & Medicine , New York, NY 10065, USA"},{"name":"Department of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, The Meyer Cancer Center , Weill Cornell Medicine of Cornell University, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Seidman","sequence":"additional","affiliation":[{"name":"Tri-Institutional Training Program in Computational Biology & Medicine , New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Popic","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Stanford University , Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fereydoun","family":"Hormozdiari","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, MIND Institute and Genome Center, University of California , Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serafim","family":"Batzoglou","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Stanford University , Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman","family":"Hajirasouliha","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, The Meyer Cancer Center , Weill Cornell Medicine of Cornell University, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,10,4]]},"reference":[{"key":"2023013110162962000_btz737-B1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nrg2958","article-title":"Genome structural variation discovery and genotyping","volume":"12","author":"Alkan","year":"2011","journal-title":"Nat. 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