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5 years ago
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<!doctypehtml><html dir=ltr lang=en xmlns=http://www.w3.org/1999/xhtml xmlns:mml=http://www.w3.org/1998/Math/MathML><head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#"><meta value="text/html; charset=utf-8"http-equiv=Content-Type><link href=https://stats.g.doubleclick.net/ rel=dns-prefetch><link href=https://www.google-analytics.com/ rel=dns-prefetch><link href=https://scholar.google.com/ rel=dns-prefetch><link href=https://d33xdlntwy0kbs.cloudfront.net/ rel=dns-prefetch><link href=https://www.biorxiv.org/sites/default/files/images/favicon.ico rel="shortcut icon"type=image/vnd.microsoft.icon><meta value="width=device-width, initial-scale=1, maximum-scale=3, minimum-scale=1, user-scalable=yes"name=viewport><meta value=https://www.biorxiv.org/content/biorxiv/early/2019/07/11/696633/embed/graphic-7.gif name=article_thumbnail><meta value=article name=type><meta value=article name=category><meta value=/biorxiv/early/2019/07/11/696633.atom name=HW.identifier><meta value=biorxiv;696633v1 name=HW.pisa><meta value=text/html name=DC.Format><meta value=en name=DC.Language><meta value="Sub-nucleosomal organization in urine cell-free DNA"name=DC.Title><meta value=10.1101/696633 name=DC.Identifier><meta value=2019-07-11 name=DC.Date><meta value="Cold Spring Harbor Laboratory"name=DC.Publisher><meta value="© 2019, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NonCommercial-NoDerivs 4.0 International), CC BY-NC-ND 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/"name=DC.Rights><meta value=restricted name=DC.AccessRights><meta value="Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, urine cfDNA is highly fragmented and whether characteristics of these fragments reflect underlying genomic architecture is unknown. Here, we perform comprehensive characterization of fragmentation patterns in urine cfDNA. We show modal size and genome-wide distribution of urine cfDNA fragments are consistent with transient protection from degradation by stable intermediates of nucleosome disassembly. Genome-wide nucleosome occupancy and fragment sizes in urine cfDNA are informative of cell of origin and renal epithelial cells are amongst the highest contributors in urine. Compared to a nucleosome occupancy map based on control urine samples, we observe a higher fraction of fragments with aberrant ends in cancer patients, distinguishing cancer samples with an area under the curve of 0.89. Our results demonstrate sub-nucleosomal organization in urine cfDNA and are proof-of-principle that genome-wide fragmentation analysis of urine cfDNA can enable cancer diagnostics."name=DC.Description><meta value="Havell Markus"name=DC.Contributor><meta value="Jun Zhao"name=DC.Contributor><meta value="Tania Contente-Cuomo"name=DC.Contributor><meta value="Elizabeth Raupach"name=DC.Contributor><meta value="Ahuva Odenheimer-Bergman"name=DC.Contributor><meta value="Sydney Connor"name=DC.Contributor><meta value="Bradon R. McDonald"name=DC.Contributor><meta value="Elizabeth Hutchins"name=DC.Contributor><meta value="Marissa McGilvery"name=DC.Contributor><meta value="Michelina C. de la Maza"name=DC.Contributor><meta value="Kendall Van Keuren-Jensen"name=DC.Contributor><meta value="Patrick Pirrotte"name=DC.Contributor><meta value="Ajay Goel"name=DC.Contributor><meta value="Carlos Becerra"name=DC.Contributor><meta value="Daniel D. Von Hoff"name=DC.Contributor><meta value="Scott A. Celinski"name=DC.Contributor><meta value="Pooja Hingorani"name=DC.Contributor><meta value="Muhammed Murtaza"name=DC.Contributor><meta value=2019-07-11 name=article:published_time><meta value="New Results"name=article:section><meta value="Sub-nucleosomal organization in urine cell-free DNA"name=citation_title><meta value="<p>Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, urine cfDNA is highly fragmented and whether characteristics of these fragments reflect underlying genomic architect
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