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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 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.</p>"name=citation_abstract lang=en><meta value=bioRxiv name=citation_journal_title><meta value="Cold Spring Harbor Laboratory"name=citation_publisher><meta value=2019/01/01 name=citation_publication_date><meta value=biorxiv;696633v1 name=citation_mjid><meta value=696633v1 name=citation_id><meta value=https://www.biorxiv.org/content/10.1101/696633v1 name=citation_public_url><meta value=https://www.biorxiv.org/content/10.1101/696633v1.abstract name=citation_abstract_html_url><meta value=https://www.biorxiv.org/content/10.1101/696633v1.full name=citation_full_html_url><meta value=https://www.biorxiv.org/content/biorxiv/early/2019/07/11/696633.full.pdf name=citation_pdf_url><meta value=10.1101/696633 name=citation_doi><meta value=33 name=citation_num_pages><meta value=Article name=citation_article_type><meta value="New Results"name=citation_section><meta value=696633 name=citation_firstpage><meta value="Havell Markus"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Jun Zhao"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Phoenix Children’s Hospital"name=citation_author_institution><meta value="Tania Contente-Cuomo"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Elizabeth Raupach"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value=http://orcid.org/0000-0002-6034-007X name=citation_author_orcid><meta value="Ahuva Odenheimer-Bergman"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Sydney Connor"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Bradon R. McDonald"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Elizabeth Hutchins"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Marissa McGilvery"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Michelina C. de la Maza"name=citation_author><meta value="Phoenix Children’s Hospital"name=citation_author_institution><meta value="Kendall Van Keuren-Jensen"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Patrick Pirrotte"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Ajay Goel"name=citation_author><meta value="Baylor Scott & White Research Institute, Baylor University Medical Center"name=citation_author_institution><meta value="Carlos Becerra"name=citation_author><meta value="Baylor Scott & White Research Institute, Baylor University Medical Center"name=citation_author_institution><meta value="Daniel D. Von Hoff"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value="Scott A. Celinski"name=citation_author><meta value="Baylor Scott & White Research Institute, Baylor University Medical Center"name=citation_author_institution><meta value="Pooja Hingorani"name=citation_author><meta value="Phoenix Children’s Hospital"name=citation_author_institution><meta value="Muhammed Murtaza"name=citation_author><meta value="Translational Genomics Research Institute"name=citation_author_institution><meta value=mmurtaza@tgen.org name=citation_author_email><meta value=http://orcid.org/0000-0001-7557-2861 name=citation_author_orcid><meta value="Murtaza, M. & Caldas, C. Nucleosome mapping in plasma DNA predicts cancer gene expression. Nat Genet 48, 1105–1106, doi:10.1038/ng.3686 (2016)."name=citation_reference><meta value="Cristiano, S. et al. Genome-wide cell-free DNA fragmentation in patients with cancer. 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J Am Soc Mass Spectrom 27, 1719–1727, doi:10.1007/s13361-016-1460-7 (2016)."name=citation_reference><meta value="Sub-nucleosomal organization in urine cell-free DNA"name=twitter:title><meta value=@biorxivpreprint name=twitter:site><meta value=summary name=twitter:card><meta value=https://www.biorxiv.org/sites/default/files/images/biorxiv_logo_homepage7-5-small.png name=twitter:image><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=twitter:description><meta value="Sub-nucleosomal organization in urine cell-free DNA"name=og:title><meta value=https://www.biorxiv.org/content/10.1101/696633v1 name=og:url><meta value=bioRxiv name=og:site_name><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=og:description><meta value=article name=og:type><meta value=https://www.biorxiv.org/sites/default/files/images/biorxiv_logo_homepage7-5-small.png name=og:image><meta value=2019-07-11 name=citation_date><link href=https://biorxiv.org/content/10.1101/696633v1.full.pdf rel=alternate type=application/pdf title="Full Text (PDF)"><link href=https://biorxiv.org/content/10.1101/696633v1.full.txt rel=alternate type=text/plain title="Full Text (Plain)"><link href=https://biorxiv.org/content/10.1101/696633v1.ppt rel=alternate type=application/vnd.ms-powerpoint title=Powerpoint><meta value="bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution"name=description><meta value="Drupal 7 (http://drupal.org)"name=generator><link 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highwire-citation-type-highwire-article"id=node814058 data-apath=/biorxiv/early/2019/07/11/696633.atom data-node-nid=814058 data-pisa=biorxiv;696633v1 data-pisa-master=biorxiv;696633 data-hw-author-tooltip-instance=highwire_author_tooltip><div class="clearfix highwire-cite highwire-cite-highwire-article has-author-tooltip highwire-citation-biorxiv-article-top"><span class=biorxiv-article-type>New Results</span><h1 class=highwire-cite-title id=page-title>Sub-nucleosomal organization in urine cell-free DNA</h1><div class=highwire-cite-authors><span class=highwire-citation-authors><span class="highwire-citation-author first"data-delta=0><span class=nlm-given-names>Havell</span> <span class=nlm-surname>Markus</span></span>, <span class=highwire-citation-author data-delta=1><span class=nlm-given-names>Jun</span> <span class=nlm-surname>Zhao</span></span>, <span class=highwire-citation-author data-delta=2><span class=nlm-given-names>Tania</span> <span class=nlm-surname>Contente-Cuomo</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper"data-delta=3><a href=http://orcid.org/0000-0002-6034-007X class="link-icon hw-author-orcid-logo link-icon-only"target=_blank><i class="hw-icon-color-orcid hw-icon-orcid"></i> <span class="title element-invisible">View ORCID Profile</span></a><span class=nlm-given-names>Elizabeth</span> <span class=nlm-surname>Raupach</span></span>, <span class=highwire-citation-author data-delta=4><span class=nlm-given-names>Ahuva</span> <span class=nlm-surname>Odenheimer-Bergman</span></span>, <span class=highwire-citation-author data-delta=5><span class=nlm-given-names>Sydney</span> <span class=nlm-surname>Connor</span></span>, <span class=highwire-citation-author data-delta=6><span class=nlm-given-names>Bradon R.</span> <span class=nlm-surname>McDonald</span></span>, <span class=highwire-citation-author data-delta=7><span class=nlm-given-names>Elizabeth</span> <span class=nlm-surname>Hutchins</span></span>, <span class=highwire-citation-author data-delta=8><span class=nlm-given-names>Marissa</span> <span class=nlm-surname>McGilvery</span></span>, <span class=highwire-citation-author data-delta=9><span class=nlm-given-names>Michelina C.</span> <span class=nlm-surname>de la Maza</span></span>, <span class=highwire-citation-author data-delta=10><span class=nlm-given-names>Kendall</span> <span class=nlm-surname>Van Keuren-Jensen</span></span>, <span class=highwire-citation-author data-delta=11><span class=nlm-given-names>Patrick</span> <span class=nlm-surname>Pirrotte</span></span>, <span class=highwire-citation-author data-delta=12><span class=nlm-given-names>Ajay</span> <span class=nlm-surname>Goel</span></span>, <span class=highwire-citation-author data-delta=13><span class=nlm-given-names>Carlos</span> <span class=nlm-surname>Becerra</span></span>, <span class=highwire-citation-author data-delta=14><span class=nlm-given-names>Daniel D.</span> <span class=nlm-surname>Von Hoff</span></span>, <span class=highwire-citation-author data-delta=15><span class=nlm-given-names>Scott A.</span> <span class=nlm-surname>Celinski</span></span>, <span class=highwire-citation-author data-delta=16><span class=nlm-given-names>Pooja</span> <span class=nlm-surname>Hingorani</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper"data-delta=17><a href=http://orcid.org/0000-0001-7557-2861 class="link-icon hw-author-orcid-logo link-icon-only"target=_blank><i class="hw-icon-color-orcid hw-icon-orcid"></i> <span class="title element-invisible">View ORCID Profile</span></a><span class=nlm-given-names>Muhammed</span> <span class=nlm-surname>Murtaza</span></span></span></div><div class=highwire-cite-metadata><span class="highwire-cite-metadata highwire-cite-metadata-doi"><span class=label>doi:</span> https://doi.org/10.1101/696633</span></div></div><div id=hw-article-author-popups-node814058 style=display:none><div class=author-tooltip-0><div class=author-tooltip-name>Havell Markus</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-1>Translational Genomics Research Institute</span>, Phoenix, AZ, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=H.%2BMarkus"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=Markus%20H&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last author-site-search-link"><a href=https://biorxiv.org/search/author1%3AHavell%2BMarkus data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this site</a></ul></div><div class=author-tooltip-1><div class=author-tooltip-name>Jun Zhao</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-1>Translational Genomics Research Institute</span>, Phoenix, AZ, <span class=nlm-country>USA</span></span><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-2>Phoenix Children’s Hospital</span>, Phoenix, AZ, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=J.%2BZhao"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a 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author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=Contente-Cuomo%20T&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last author-site-search-link"><a href=https://biorxiv.org/search/author1%3ATania%2BContente-Cuomo data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this site</a></ul></div><div class=author-tooltip-3><div class=author-tooltip-name>Elizabeth Raupach</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-1>Translational Genomics Research Institute</span>, Phoenix, AZ, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=E.%2BRaupach"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=Raupach%20E&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class=author-site-search-link><a href=https://biorxiv.org/search/author1%3AElizabeth%2BRaupach data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this site</a><li class="last author-orcid-link"><a href=http://orcid.org/0000-0002-6034-007X data-hide-link-title=0 data-icon-position=""target=_blank>ORCID record for Elizabeth Raupach</a></ul></div><div class=author-tooltip-4><div class=author-tooltip-name>Ahuva Odenheimer-Bergman</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-1>Translational Genomics Research Institute</span>, Phoenix, AZ, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=A.%2BOdenheimer-Bergman"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=Odenheimer-Bergman%20A&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last author-site-search-link"><a href=https://biorxiv.org/search/author1%3AAhuva%2BOdenheimer-Bergman data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this site</a></ul></div><div class=author-tooltip-5><div class=author-tooltip-name>Sydney Connor</div><div 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class=author-tooltip-6><div class=author-tooltip-name>Bradon R. McDonald</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-1>Translational Genomics Research Institute</span>, Phoenix, AZ, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=B.%20R.%2BMcDonald"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=McDonald%20BR&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last author-site-search-link"><a href=https://biorxiv.org/search/author1%3ABradon%2BR.%2BMcDonald data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this 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data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this site</a></ul></div><div class=author-tooltip-8><div class=author-tooltip-name>Marissa McGilvery</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-1>Translational Genomics Research Institute</span>, Phoenix, AZ, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=M.%2BMcGilvery"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=McGilvery%20M&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last 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href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=A.%2BGoel"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=Goel%20A&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last author-site-search-link"><a href=https://biorxiv.org/search/author1%3AAjay%2BGoel data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this site</a></ul></div><div class=author-tooltip-13><div class=author-tooltip-name>Carlos Becerra</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-3>Baylor Scott & White Research Institute, Baylor University Medical Center</span>, Dallas, TX, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=C.%2BBecerra"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=Becerra%20C&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last author-site-search-link"><a href=https://biorxiv.org/search/author1%3ACarlos%2BBecerra data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this site</a></ul></div><div class=author-tooltip-14><div class=author-tooltip-name>Daniel D. Von Hoff</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-1>Translational Genomics Research Institute</span>, Phoenix, AZ, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=D.%20D.%2BVon%20Hoff"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=Von%20Hoff%20DD&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last author-site-search-link"><a href=https://biorxiv.org/search/author1%3ADaniel%2BD.%2BVon%2BHoff data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this site</a></ul></div><div class=author-tooltip-15><div class=author-tooltip-name>Scott A. Celinski</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-3>Baylor Scott & White Research Institute, Baylor University Medical Center</span>, Dallas, TX, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=S.%20A.%2BCelinski"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=Celinski%20SA&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last author-site-search-link"><a href=https://biorxiv.org/search/author1%3AScott%2BA.%2BCelinski data-hide-link-title=0 data-icon-position=""rel=nofollow>Search for this author on this site</a></ul></div><div class=author-tooltip-16><div class=author-tooltip-name>Pooja Hingorani</div><div class=author-tooltip-affiliation><span class=author-tooltip-text><span class=nlm-aff><span class=nlm-institution data-hwp-id=institution-2>Phoenix Children’s Hospital</span>, Phoenix, AZ, <span class=nlm-country>USA</span></span></span></div><ul class=author-tooltip-find-more><li class="first author-tooltip-gs-link"><a href="https://biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=P.%2BHingorani"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on Google Scholar</a><li class=author-tooltip-pubmed-link><a href="https://biorxiv.org/lookup/external-ref?access_num=Hingorani%20P&link_type=AUTHORSEARCH"data-hide-link-title=0 data-icon-position=""target=_blank>Find this author on PubMed</a><li class="last author-site-search-link"><a href=https://biorxiv.org/search/author1%3APooja%2BHingorani 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data-url-enabled=1><i class=icon-file-alt></i> Preview PDF</a><a href=https://biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:814058/1 class=js-crawler-link rel=nofollow style=display:none></a></ul></div></div></div><div class=panel-separator></div><div class="panel-pane pane-highwire-panel-tabs-container"><div class=pane-content><div class=panels-ajax-tab-container id=panels-ajax-tab-container-highwire_article_tabs data-panels-ajax-tab-preloaded=biorxiv_tab_art><div class=panels-ajax-tab-loading style=display:none><img alt=Loading src=https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif class=loading title=Loading></div><div class=panels-ajax-tab-wrap-biorxiv_tab_art><div class="clearfix panel-1col panel-display"><div class="panel-panel panel-col"><div><div class="panel-pane pane-highwire-markup"><div class=pane-content><div class=highwire-markup><div id=content-block-markup data-highwire-cite-ref-tooltip-instance=highwire_reflinks_tooltip xmlns=http://www.w3.org/1999/xhtml xmlns:xhtml=http://www.w3.org/1999/xhtml><div class="abstract-view article"><span class=highwire-journal-article-marker-start></span><div class="section abstract"id=abstract-1><h2>Abstract</h2><p id=p-2>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.</div><span class=highwire-journal-article-marker-end></span></div><span id=related-urls></span></div></div></div></div><div class=panel-separator></div><div class="panel-pane pane-biorxiv-copyright"><div class=pane-content><div class="clearfix field field-label-inline field-name-field-highwire-copyright field-type-text"><div class=field-label>Copyright </div><div class=field-items><div class="even field-item">The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.<span class=license-type> It is made available under a <a href=http://creativecommons.org/licenses/by-nc-nd/4.0/ data-hide-link-title=0 data-icon-position="">CC-BY-NC-ND 4.0 International 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class=highwire-citation-author data-delta=8><span class=nlm-given-names>Marissa</span> <span class=nlm-surname>McGilvery</span></span>, <span class=highwire-citation-author data-delta=9><span class=nlm-given-names>Michelina C.</span> <span class=nlm-surname>de la Maza</span></span>, <span class=highwire-citation-author data-delta=10><span class=nlm-given-names>Kendall</span> <span class=nlm-surname>Van Keuren-Jensen</span></span>, <span class=highwire-citation-author data-delta=11><span class=nlm-given-names>Patrick</span> <span class=nlm-surname>Pirrotte</span></span>, <span class=highwire-citation-author data-delta=12><span class=nlm-given-names>Ajay</span> <span class=nlm-surname>Goel</span></span>, <span class=highwire-citation-author data-delta=13><span class=nlm-given-names>Carlos</span> <span class=nlm-surname>Becerra</span></span>, <span class=highwire-citation-author data-delta=14><span class=nlm-given-names>Daniel D.</span> <span class=nlm-surname>Von Hoff</span></span>, <span class=highwire-citation-author data-delta=15><span class=nlm-given-names>Scott A.</span> <span class=nlm-surname>Celinski</span></span>, <span class=highwire-citation-author data-delta=16><span class=nlm-given-names>Pooja</span> <span class=nlm-surname>Hingorani</span></span>, <span class=highwire-citation-author data-delta=17><span class=nlm-given-names>Muhammed</span> <span class=nlm-surname>Murtaza</span></span></span></div><div class=highwire-cite-metadata><span class="highwire-cite-metadata highwire-cite-metadata-journal">bioRxiv </span><span class="highwire-cite-metadata highwire-cite-metadata-pages">696633; </span><span class="highwire-cite-metadata highwire-cite-metadata-doi"><span class=doi_label>doi:</span> https://doi.org/10.1101/696633</span></div></div></div></div><div class=highwire-citation-formats><h2>Citation Manager Formats</h2><div class=highwire-citation-formats-links><span class=Z3988 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