{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T09:16:38Z","timestamp":1692436598129},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: DNA methylation aberrations are now known to, almost universally, accompany the initiation and progression of cancers. In particular, the colon cancer epigenome contains specific genomic regions that, along with differences in methylation levels with respect to normal colon tissue, also show increased epigenetic and gene expression heterogeneity at the population level, i.e. across tumor samples, in comparison with other regions in the genome. Tumors are highly heterogeneous at the clonal level as well, and the relationship between clonal and population heterogeneity is poorly understood.<\/jats:p>\n               <jats:p>Results: We present an approach that uses sequencing reads from high-throughput sequencing of bisulfite-converted DNA to reconstruct heterogeneous cell populations by assembling cell-specific methylation patterns. Our methodology is based on the solution of a specific class of minimum cost network flow problems. We use our methods to analyze the relationship between clonal heterogeneity and population heterogeneity in high-coverage data from multiple samples of colon tumor and matched normal tissues.<\/jats:p>\n               <jats:p>Availability and implementation: http:\/\/github.com\/hcorrada\/methylFlow.<\/jats:p>\n               <jats:p>Contact: \u00a0hcorrada@umiacs.umd.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary information is available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw287","type":"journal-article","created":{"date-parts":[[2016,5,31]],"date-time":"2016-05-31T06:32:37Z","timestamp":1464676357000},"page":"1618-1624","source":"Crossref","is-referenced-by-count":5,"title":["methylFlow: cell-specific methylation pattern reconstruction from high-throughput bisulfite-converted DNA sequencing"],"prefix":"10.1093","volume":"32","author":[{"given":"Faezeh","family":"Dorri","sequence":"first","affiliation":[{"name":"1 Center for Bioinformatics and Computational Biology"},{"name":"2 Department of Computer Science"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Mendelowitz","sequence":"additional","affiliation":[{"name":"1 Center for Bioinformatics and Computational Biology"},{"name":"3 Applied Mathematics, Statistics and Scientific Compoutation Program, University of Maryland, College Park, MD 20745, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor","family":"Corrada Bravo","sequence":"additional","affiliation":[{"name":"1 Center for Bioinformatics and Computational Biology"},{"name":"2 Department of Computer Science"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,5,28]]},"reference":[{"key":"2023020112283958100_btw287-B1","first-page":"2447","article-title":"Efficient RNA isoform identification and quantification from RNA-Seq data with network flows","volume":"30","author":"Bernard","year":"2014","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020112283958100_btw287-B2","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ygeno.2011.07.007","article-title":"High density DNA methylation array with single CpG site resolution","volume":"98","author":"Bibikova","year":"2011","journal-title":"Genomics"},{"key":"2023020112283958100_btw287-B3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.entcs.2011.06.003","article-title":"Lemon\u2013an open source c\u2009++ graph template library","volume":"264","author":"Dezs\u0151","year":"2011","journal-title":"Electron. Notes Theor. Comput. Sci"},{"key":"2023020112283958100_btw287-B4","doi-asserted-by":"crossref","first-page":"e1000074.","DOI":"10.1371\/journal.pcbi.1000074","article-title":"Viral population estimation using pyrosequencing","volume":"4","author":"Eriksson","year":"2008","journal-title":"PLOS Comput. Biol"},{"key":"2023020112283958100_btw287-B5","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1093\/bioinformatics\/btv020","article-title":"Methylmix: an R package for identifying DNA methylation-driven genes","volume":"31","author":"Gevaert","year":"2015","journal-title":"Bioinformatics"},{"key":"2023020112283958100_btw287-B6","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/ng.865","article-title":"Increased methylation variation in epigenetic domains across cancer types","volume":"43","author":"Hansen","year":"2011","journal-title":"Nat. Genet"},{"key":"2023020112283958100_btw287-B7","doi-asserted-by":"crossref","first-page":"R83.","DOI":"10.1186\/gb-2012-13-10-r83","article-title":"BSmooth: from whole genome bisulfite sequencing reads to differentially methylated regions","volume":"13","author":"Hansen","year":"2012","journal-title":"Genome Biol"},{"key":"2023020112283958100_btw287-B8","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1126\/science.187.4173.226","article-title":"DNA modification mechanisms and gene activity during development","volume":"187","author":"Holliday","year":"1975","journal-title":"Science (New York, NY)"},{"key":"2023020112283958100_btw287-B9","doi-asserted-by":"crossref","first-page":"86.","DOI":"10.1186\/1471-2105-13-86","article-title":"DNA methylation arrays as surrogate measures of cell mixture distribution","volume":"13","author":"Houseman","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"2023020112283958100_btw287-B10","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1101\/gr.7301508","article-title":"Comprehensive high-throughput arrays for relative methylation (CHARM)","volume":"18","author":"Irizarry","year":"2008","journal-title":"Genome Res"},{"key":"2023020112283958100_btw287-B11","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/ije\/dyr238","article-title":"Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies","volume":"41","author":"Jaffe","year":"2012","journal-title":"Int. J. Epidemiol"},{"key":"2023020112283958100_btw287-B12","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.cell.2013.11.039","article-title":"Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation","volume":"155","author":"Kieffer-Kwon","year":"2013","journal-title":"Cell"},{"key":"2023020112283958100_btw287-B13","first-page":"1571","article-title":"Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications","volume":"27","author":"Krueger","year":"2011","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020112283958100_btw287-B14","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1038\/ng.2442","article-title":"Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues","volume":"44","author":"Landan","year":"2012","journal-title":"Nat. Genet"},{"key":"2023020112283958100_btw287-B15","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1089\/cmb.2011.0171","article-title":"Isolasso: a lasso regression approach to RNA-Seq based transcriptome assembly","volume":"18","author":"Li","year":"2011","journal-title":"J. Comput. Biol"},{"key":"2023020112283958100_btw287-B16","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nature08514","article-title":"Human DNA methylomes at base resolution show widespread epigenomic differences","volume":"462","author":"Lister","year":"2009","journal-title":"Nature"},{"key":"2023020112283958100_btw287-B17","volume-title":"Introduction to Linear and Nonlinear Programming","author":"Luenberger","year":"1973"},{"key":"2023020112283958100_btw287-B18","author":"Makhorin","year":"2008"},{"key":"2023020112283958100_btw287-B19","doi-asserted-by":"crossref","first-page":"5868","DOI":"10.1093\/nar\/gki901","article-title":"Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis","volume":"33","author":"Meissner","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023020112283958100_btw287-B20","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/nmeth.3035","article-title":"Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity","volume":"11","author":"Smallwood","year":"2014","journal-title":"Nat. Methods"},{"key":"2023020112283958100_btw287-B21","doi-asserted-by":"crossref","first-page":"61.","DOI":"10.1186\/s13073-014-0061-y","article-title":"Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors","volume":"6","author":"Timp","year":"2014","journal-title":"Genome Med"},{"key":"2023020112283958100_btw287-B22","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1186\/s13059-014-0419-x","article-title":"Methylpurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes","volume":"15","author":"Zheng","year":"2014","journal-title":"Genome Biol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/11\/1618\/49019205\/bioinformatics_32_11_1618.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/11\/1618\/49019205\/bioinformatics_32_11_1618.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T22:31:58Z","timestamp":1675290718000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/32\/11\/1618\/1743421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,28]]},"references-count":22,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2016,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btw287","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2016,6,1]]},"published":{"date-parts":[[2016,5,28]]}}}