{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:39:24Z","timestamp":1761863964727},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T00:00:00Z","timestamp":1562544000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Ministry of Science","award":["No.NRF-2017M3C4A7065887"],"award-info":[{"award-number":["No.NRF-2017M3C4A7065887"]}]},{"name":"ICT","award":["No.NRF2014M3C9A3063541"],"award-info":[{"award-number":["No.NRF2014M3C9A3063541"]}]},{"name":"Ministry of Health & Welfare, Republic of Korea","award":["HI15C3224"],"award-info":[{"award-number":["HI15C3224"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Characterizing cancer subclones is crucial for the ultimate conquest of cancer. Thus, a number of bioinformatic tools have been developed to infer heterogeneous tumor populations based on genomic signatures such as mutations and copy number variations. Despite accumulating evidence for the significance of global DNA methylation reprogramming in certain cancer types including myeloid malignancies, none of the bioinformatic tools are designed to exploit subclonally reprogrammed methylation patterns to reveal constituent populations of a tumor. In accordance with the notion of global methylation reprogramming, our preliminary observations on acute myeloid leukemia (AML) samples implied the existence of subclonally occurring focal methylation aberrance throughout the genome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We present PRISM, a tool for inferring the composition of epigenetically distinct subclones of a tumor solely from methylation patterns obtained by reduced representation bisulfite sequencing. PRISM adopts DNA methyltransferase 1-like hidden Markov model-based in silico proofreading for the correction of erroneous methylation patterns. With error-corrected methylation patterns, PRISM focuses on a short individual genomic region harboring dichotomous patterns that can be split into fully methylated and unmethylated patterns. Frequencies of such two patterns form a sufficient statistic for subclonal abundance. A set of statistics collected from each genomic region is modeled with a beta-binomial mixture. Fitting the mixture with expectation-maximization algorithm finally provides inferred composition of subclones. Applying PRISM for two AML samples, we demonstrate that PRISM could infer the evolutionary history of malignant samples from an epigenetic point of view.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>PRISM is freely available on GitHub (https:\/\/github.com\/dohlee\/prism).<\/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\/btz327","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T11:20:03Z","timestamp":1557400803000},"page":"i520-i529","source":"Crossref","is-referenced-by-count":13,"title":["PRISM: methylation pattern-based, reference-free inference of subclonal makeup"],"prefix":"10.1093","volume":"35","author":[{"given":"Dohoon","family":"Lee","sequence":"first","affiliation":[{"name":"Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Korea"}]},{"given":"Sangseon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, Seoul National University, Seoul, Korea"}]},{"given":"Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Korea"},{"name":"Department of Computer Science and Engineering, Seoul National University, Seoul, Korea"},{"name":"Bioinformatics Institute, Seoul National University, Seoul, Korea"}]}],"member":"286","published-online":{"date-parts":[[2019,7,5]]},"reference":[{"key":"2023062712322086500_btz327-B1","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.celrep.2013.12.041","article-title":"Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity","volume":"6","author":"Almendro","year":"2014","journal-title":"Cell Rep"},{"key":"2023062712322086500_btz327-B2","doi-asserted-by":"crossref","first-page":"354.","DOI":"10.1186\/s12859-017-1753-2","article-title":"Quantification of tumour evolution and heterogeneity via Bayesian epiallele detection","volume":"18","author":"Barrett","year":"2017","journal-title":"BMC Bioinform"},{"key":"2023062712322086500_btz327-B3","doi-asserted-by":"crossref","first-page":"726.","DOI":"10.1038\/nrc3130","article-title":"A decade of exploring the cancer epigenome-biological and translational implications","volume":"11","author":"Baylin","year":"2011","journal-title":"Nat. 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