CellLoop: Identifying single-cell 3D genome chromatin loops | 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 CellLoop: Identifying single-cell 3D genome chromatin loops Yusen Ye, Yuxuan Hu, Liang Yu, Weibing Wang, Shihua Zhang, Hebing Chen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6930366/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 Single-cell 3D genome technologies provide unprecedented views of chromatin architecture, but the extreme sparsity and noise of contact maps limit robust detection of chromatin loops at the individual cell level. Here we present CellLoop, a computational framework for identifying chromatin loops from single-cell contact data by integrating intra-cellular and neighboring inter-cellular contacts through a density-based voting strategy. Applied to Dip-C data from the mouse brain, CellLoop achieves improved loop resolution consistent with spatial distances and compartmentalization signals, revealing single cell-specific chromatin loops associated with transcriptional regulation and cell identity. In HiRES embryogenesis data, CellLoop enables finer cell subtype delineation by reducing confounding cell cycle effects. When integrated with GAGE-seq and MERFISH in the mouse cortex, CellLoop redefines spatial domain functions through chromatin loop dynamics. These findings establish CellLoop as a scalable and accurate approach for dissecting chromatin loop dynamics at single-cell resolution, and demonstrate the utility of 3D genome features in interpreting transcriptional and spatial cell state heterogeneity. Biological sciences/Computational biology and bioinformatics/Data mining Biological sciences/Genetics/Genomics single-cell chromatin loops loop frequency map spatial domains density-based peak sweeping Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTables.xlsx Supplementary Tables SupplementaryNotes.docx Supplementary Results and Methods 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. 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-6930366","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":478268620,"identity":"17da7bf0-b819-4c76-b7ce-77d6761b7faf","order_by":0,"name":"Yusen Ye","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYLCCDwwSjG1gFhuROhhnkKyFmQeorYFoLQbnzxg+tm2zkO1jP3uA4UPZYQb+2Q0EtNzIMTbOOSNh3MaTl8A449xhBok7Bwhp4TGTzqmQSGxjyDFg5m07zGAgkUDQYea/LQyAWvjfGDD/JUrLgRwzZgaQLRJAWxiJ0SJ5I61YsgfkF4k3Bgd7zqXzSNwgoIXv/OGNH3621cnO788xfPCjzFqOfwYBLQoHOAzgnANAzINfPRDIN7A/IKhoFIyCUTAKRjgAAKUPQOfpVhaKAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-8687-1058","institution":"School of Computer Science and Technology, Xidian University","correspondingAuthor":true,"prefix":"","firstName":"Yusen","middleName":"","lastName":"Ye","suffix":""},{"id":478268621,"identity":"29c7caa1-0949-41c4-a2e1-4f3f67ab1830","order_by":1,"name":"Yuxuan Hu","email":"","orcid":"","institution":"School of Computer Science and Technology, Xidian University","correspondingAuthor":false,"prefix":"","firstName":"Yuxuan","middleName":"","lastName":"Hu","suffix":""},{"id":478268622,"identity":"67e63a96-a5be-469f-81e6-ba553dad20f8","order_by":2,"name":"Liang Yu","email":"","orcid":"","institution":"School of Computer Science and Technology, Xidian University","correspondingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Yu","suffix":""},{"id":478268623,"identity":"24dbf2e0-5ac2-4fcc-9faf-983599d0a146","order_by":3,"name":"Weibing Wang","email":"","orcid":"","institution":"School of Computer Science and Technology, Xidian University","correspondingAuthor":false,"prefix":"","firstName":"Weibing","middleName":"","lastName":"Wang","suffix":""},{"id":478268624,"identity":"088a07aa-675e-4799-9c82-daf95880e675","order_by":4,"name":"Shihua Zhang","email":"","orcid":"https://orcid.org/0000-0003-0192-7118","institution":"Academy of Mathematics and Systems Science, CAS","correspondingAuthor":false,"prefix":"","firstName":"Shihua","middleName":"","lastName":"Zhang","suffix":""},{"id":478268625,"identity":"f233da62-cf58-42f2-bb8e-3a85347b360e","order_by":5,"name":"Hebing Chen","email":"","orcid":"https://orcid.org/0000-0003-4102-356X","institution":"Academy of Military Medical Sciences, Beijing, 100850, P.R.China.","correspondingAuthor":false,"prefix":"","firstName":"Hebing","middleName":"","lastName":"Chen","suffix":""},{"id":478268626,"identity":"ff6508b4-14b3-43e7-a1cd-da901f5f0882","order_by":6,"name":"Lin Gao","email":"","orcid":"","institution":"Xidian University","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Gao","suffix":""}],"badges":[],"createdAt":"2025-06-19 10:48:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6930366/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6930366/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86624491,"identity":"9cbbdc49-2082-4ea8-ac0b-1512795a6b0f","added_by":"auto","created_at":"2025-07-14 04:49:44","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5335444,"visible":true,"origin":"","legend":"Article File","description":"","filename":"CellLoopNew.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6930366/v1_covered_ead03fd9-3f8d-45ca-a208-fb74e15f6a70.pdf"},{"id":86624281,"identity":"a3f66ae2-af91-4f35-89e5-5e8d826c9db3","added_by":"auto","created_at":"2025-07-14 04:41:36","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":35001,"visible":true,"origin":"","legend":"Supplementary Tables","description":"","filename":"SupplementaryTables.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6930366/v1/8b4ffb0195335d92a21c3910.xlsx"},{"id":86624282,"identity":"31c8512a-cfa8-407a-8d87-b633bac4f4f9","added_by":"auto","created_at":"2025-07-14 04:41:36","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":7022229,"visible":true,"origin":"","legend":"Supplementary Results and Methods","description":"","filename":"SupplementaryNotes.docx","url":"https://assets-eu.researchsquare.com/files/rs-6930366/v1/c037fd545fcb965b4dccdbbe.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"CellLoop: Identifying single-cell 3D genome chromatin loops","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"single-cell chromatin loops, loop frequency map, spatial domains, density-based peak sweeping","lastPublishedDoi":"10.21203/rs.3.rs-6930366/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6930366/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Single-cell 3D genome technologies provide unprecedented views of chromatin architecture, but the extreme sparsity and noise of contact maps limit robust detection of chromatin loops at the individual cell level. Here we present CellLoop, a computational framework for identifying chromatin loops from single-cell contact data by integrating intra-cellular and neighboring inter-cellular contacts through a density-based voting strategy. Applied to Dip-C data from the mouse brain, CellLoop achieves improved loop resolution consistent with spatial distances and compartmentalization signals, revealing single cell-specific chromatin loops associated with transcriptional regulation and cell identity. In HiRES embryogenesis data, CellLoop enables finer cell subtype delineation by reducing confounding cell cycle effects. When integrated with GAGE-seq and MERFISH in the mouse cortex, CellLoop redefines spatial domain functions through chromatin loop dynamics. These findings establish CellLoop as a scalable and accurate approach for dissecting chromatin loop dynamics at single-cell resolution, and demonstrate the utility of 3D genome features in interpreting transcriptional and spatial cell state heterogeneity.","manuscriptTitle":"CellLoop: Identifying single-cell 3D genome chromatin loops","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 04:41:31","doi":"10.21203/rs.3.rs-6930366/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"68c3ee84-c9fb-4ea9-86f3-a1d375668d24","owner":[],"postedDate":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":50774692,"name":"Biological sciences/Computational biology and bioinformatics/Data mining"},{"id":50774693,"name":"Biological sciences/Genetics/Genomics"}],"tags":[],"updatedAt":"2025-07-14T04:41:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-14 04:41:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6930366","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6930366","identity":"rs-6930366","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.