{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:12Z","timestamp":1772138052169,"version":"3.50.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"US National Institutes of Health\/National Cancer Institute","award":["CA006973"],"award-info":[{"award-number":["CA006973"]}]},{"name":"US National Institutes of Health\/National Cancer Institute","award":["CA062824"],"award-info":[{"award-number":["CA062824"]}]},{"name":"US National Institutes of Health\/National Cancer Institute","award":["CA12113"],"award-info":[{"award-number":["CA12113"]}]},{"name":"US National Institutes of Health\/National Cancer Institute","award":["CA62924"],"award-info":[{"award-number":["CA62924"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K08 DK107781"],"award-info":[{"award-number":["K08 DK107781"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Allegheny Health Network-Johns Hopkins Cancer Research Fund"},{"name":"Goldman Pancreatic Cancer Research Center"},{"name":"Johns Hopkins Discovery Award"},{"name":"Medical Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Multi-region sequencing of solid tumors can improve our understanding of intratumor subclonal diversity and the evolutionary history of mutational events. Due to uncertainty in clonal composition and the multitude of possible ancestral relationships between clones, elucidating the most probable relationships from bulk tumor sequencing poses statistical and computational challenges.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We developed a Bayesian hierarchical model called PICTograph to model uncertainty in assigning mutations to subclones, to enable posterior distributions of cancer cell fractions (CCFs) and to visualize the most probable ancestral relationships between subclones. Compared with available methods, PICTograph provided more consistent and accurate estimates of CCFs and improved tree inference over a range of simulated clonal diversity. Application of PICTograph to multi-region whole-exome sequencing of tumors from individuals with pancreatic cancer precursor lesions confirmed known early-occurring mutations and indicated substantial molecular diversity, including 6\u201312 distinct subclones and intra-sample mixing of subclones. Using ensemble-based visualizations, we highlight highly probable evolutionary relationships recovered in multiple models. PICTograph provides a useful approximation to evolutionary inference from cross-sectional multi-region sequencing, particularly for complex cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>https:\/\/github.com\/KarchinLab\/pictograph. The data underlying this article will be shared on reasonable request to the corresponding author.<\/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\/btac367","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T08:14:20Z","timestamp":1654071260000},"page":"3677-3683","source":"Crossref","is-referenced-by-count":12,"title":["Estimation of cancer cell fractions and clone trees from multi-region sequencing of tumors"],"prefix":"10.1093","volume":"38","author":[{"given":"Lily","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine , Baltimore, MD 21205, USA"},{"name":"Institute for Computational Medicine, Johns Hopkins University , Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noushin","family":"Niknafs","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura D","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, MD 21287, USA"},{"name":"Department of Pathology, Johns Hopkins University School of Medicine , Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5069-1239","authenticated-orcid":false,"given":"Rachel","family":"Karchin","sequence":"additional","affiliation":[{"name":"Institute for Computational Medicine, Johns Hopkins University , Baltimore, MD 21205, USA"},{"name":"Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, MD 21287, USA"},{"name":"Department of Biomedical Engineering, Johns Hopkins University , Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4702-2656","authenticated-orcid":false,"given":"Robert B","family":"Scharpf","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"2023041405351946400_","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":"2023041405351946400_","article-title":"Calling somatic SNVs and indels with mutect2","author":"Benjamin","year":"2019","journal-title":"bioRxiv"},{"key":"2023041405351946400_","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":"2023041405351946400_","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":"2023041405351946400_","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1136\/gutjnl-2017-315062","article-title":"IPMNs with co-occurring invasive cancers: neighbours but not always relatives","volume":"67","author":"Felsenstein","year":"2018","journal-title":"Gut"},{"key":"2023041405351946400_","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1053\/j.gastro.2019.06.001","article-title":"Intraductal papillary mucinous neoplasms arise from multiple independent clones, each with distinct mutations","volume":"157","author":"Fischer","year":"2019","journal-title":"Gastroenterology"},{"key":"2023041405351946400_","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1136\/gutjnl-2020-321217","article-title":"Multiregion whole-exome sequencing of intraductal papillary mucinous neoplasms reveals frequent somatic KLF4 mutations predominantly in low-grade regions","volume":"70","author":"Fujikura","year":"2021","journal-title":"Gut"},{"key":"2023041405351946400_","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1137\/0207024","article-title":"Finding all spanning trees of directed and undirected graphs","volume":"7","author":"Gabow","year":"1978","journal-title":"SIAM J. 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