An unbiased approach to measure aberrant DNA methylation alterations

An unbiased approach to measure aberrant DNA methylation alterations | 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 Biological Sciences - Article An unbiased approach to measure aberrant DNA methylation alterations Bradley Downs, Jiumei Hu, Joon Soo Park, Hanran Lei, Tza-Huei (Jeff) Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6372690/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract The ability to accurately measure aberrant DNA methylation levels, which occur in multiple diseases including cancer, is integral to the understanding of DNA methylation biology. It is well-established that in cancer, the largest, and thus, most biologically important absolute gains of DNA methylation levels occur at CpG sites with low native levels while the largest losses occur at CpG sites with high native levels. Conventional wisdom assumes that the observed association between the degree of the alterations and the native levels are largely due to the limitations of change within the DNA methylation scale, i.e. the maximum possible gain/loss of DNA methylation depends on the native level. Here, we present evidence that this association is largely caused by alterations occurring as a global rate of change relative to the native level. We also present evidence that current approaches that measure alterations as an absolute level change have an implicit bias for the native level, which has likely skewed our understanding of DNA methylation biology. We found that DNA methylation alterations can be accurately compared by calculating the rate of change relative to the native level. Most importantly, this approach enables the identification of more biologically significant DNA methylation alterations. Biological sciences/Molecular biology/Epigenetics/DNA methylation Biological sciences/Cancer/Cancer genetics/Cancer epigenetics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files RelMethSupTables.xlsx Supplementary Table S1-12 RelMethSupFigures.pdf Supplementary Figure S1-10 Cite Share Download PDF Status: Under Review 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. 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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-6372690","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":441158860,"identity":"edab816e-ceff-493e-9b53-baf45e7534ce","order_by":0,"name":"Bradley 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