Extracting Regulatory Active Chromatin Footprint from Cell-Free DNA

Extracting Regulatory Active Chromatin Footprint from Cell-Free DNA | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Extracting Regulatory Active Chromatin Footprint from Cell-Free DNA Kevin Lai, Katharine Dilger, Rachael Cunningham, Kathy Lam, Rhea Boquiren, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3983393/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Sep, 2024 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract Cell-free DNA (cfDNA) has emerged as a pivotal player in precision medicine, revolutionizing the diagnostic and therapeutic landscape. While its clinical applications have significantly increased in recent years, current cfDNA assays have limited ability to identify the active transcriptional programs that govern complex disease phenotypes and capture the heterogeneity of the disease. To address these limitations, we have developed a non-invasive platform to enrich and examine the active chromatin fragments (cfDNA ac ) in peripheral blood. The deconvolution of the cfDNA ac signal from traditional nucleosomal chromatin fragments (cfDNA nuc ) yields a catalog of features linking these circulating chromatin signals in blood to specific regulatory elements across the genome, including enhancers, promoters, and highly transcribed genes, mirroring the epigenetic data from the ENCODE project. Notably, these cfDNA ac counts correlate strongly with RNA polymerase II activity and exhibit distinct expression patterns for known circadian genes. Additionally, cfDNA ac signals across gene bodies and promoters show strong correlations with whole blood gene expression levels defined by GTEx. This study illustrates the utility of cfDNA ac analysis for investigating epigenomics and gene expression, underscoring its potential for a wide range of clinical applications in precision medicine. Biological sciences/Biotechnology/Genomics/Personalized medicine Biological sciences/Biotechnology/Genomics/Epigenomics Biological sciences/Biotechnology/Genomics/Transcriptomics Full Text Additional Declarations Yes there is potential Competing Interest. D.A. and R.R. are co-founders and shareholders of Aqtual, Inc. All other authors are shareholders of Aqtual, Inc. Supplementary Files SupplementaryTableS1.xlsx SupplementaryTableS2.xlsx Cite Share Download PDF Status: Published Journal Publication published 04 Sep, 2024 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3983393","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":275422946,"identity":"b764f482-d432-45ed-9d2f-2cad16bf3532","order_by":0,"name":"Kevin Lai","email":"","orcid":"","institution":"Aqtual Inc.","correspondingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"","lastName":"Lai","suffix":""},{"id":275422947,"identity":"88f40726-ef07-46eb-8b68-e4bade102479","order_by":1,"name":"Katharine Dilger","email":"","orcid":"","institution":"Aqtual 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While its clinical applications have significantly increased in recent years, current cfDNA assays have limited ability to identify the active transcriptional programs that govern complex disease phenotypes and capture the heterogeneity of the disease. To address these limitations, we have developed a non-invasive platform to enrich and examine the active chromatin fragments (cfDNA\u003csub\u003eac\u003c/sub\u003e) in peripheral blood. The deconvolution of the cfDNA\u003csub\u003eac\u003c/sub\u003e signal from traditional nucleosomal chromatin fragments (cfDNA\u003csub\u003enuc\u003c/sub\u003e) yields a catalog of features linking these circulating chromatin signals in blood to specific regulatory elements across the genome, including enhancers, promoters, and highly transcribed genes, mirroring the epigenetic data from the ENCODE project. 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