Dissecting Tissue Architecture and Function through Mapping of Cellular Communication Networks | 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 Dissecting Tissue Architecture and Function through Mapping of Cellular Communication Networks Lin Hou, Dongyu Li, Ming Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6920553/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 Spatial transcriptome provides critical insights for inferring cell-cell communications. Based on the heuristic that physically adjacent cells are more likely to communicate with each other, we develop a computational framework that Infers the Cell-Cell Communication network (IC3) and subsequently identifies communication hotspots with rigorous error control. We demonstrate in simulations and real datasets that our method outperforms existing methods in accuracy and especially improves sensitivity to identify communications involving rare cell types. Applying IC3 in a mouse brain dataset, we recovered how cells communicate with each other to form a local structure that regulates the balance of the blood-brain barrier. These findings highlight that our method is effective in revealing tissue architecture and function from cellular communication networks. Biological sciences/Computational biology and bioinformatics/Cellular signalling networks Biological sciences/Neuroscience/Cellular neuroscience Biological sciences/Biotechnology/Genomics/Transcriptomics cellular communication network Poisson graphical model scan hotspot Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementary0618.pdf Dissecting Tissue Architecture and Function through Mapping of Cellular Communication Networks 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-6920553","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":476353148,"identity":"ec8223e2-3932-4dff-86fd-bf73f4c464a4","order_by":0,"name":"Lin Hou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYBACAwYGxgMfGBh4wAgIGBuI0MJwcEYCqVoO8ySAmMRqMWfvMThs+6NOxpx/7TGJHww2shsOMD97gE+LZc8Zg8M5CYd5LGe8S5PsYUgz3nCAzdwAr8Nu5IC0HOAxuHHGTIKH4XDihgM8bBIEtVgk1IG1SP5h+E+kFoYEZh6D8z1m0jwMB4jQcuZYwcGetMNAW3iMrWUMko1nHmYzw6/lePPGBz9s6uwNzp8xvPmmwk6273jzM7xaEEAigQESTczEqQcC/gNEKx0Fo2AUjIIRBgCXSUrdvK0zRQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-4283-8501","institution":"Tsinghua University","correspondingAuthor":true,"prefix":"","firstName":"Lin","middleName":"","lastName":"Hou","suffix":""},{"id":476353149,"identity":"8c825dba-e905-443a-b149-934cc3a5fc7a","order_by":1,"name":"Dongyu Li","email":"","orcid":"","institution":"Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Dongyu","middleName":"","lastName":"Li","suffix":""},{"id":476353150,"identity":"3fd233d9-6dfa-45f2-b93c-accb60a152cc","order_by":2,"name":"Ming Yang","email":"","orcid":"","institution":"Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2025-06-18 08:06:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6920553/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6920553/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88293776,"identity":"c915d106-c134-426a-8d04-4274e70ff380","added_by":"auto","created_at":"2025-08-05 02:53:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2036341,"visible":true,"origin":"","legend":"Article File","description":"","filename":"IC3main.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6920553/v1_covered_a893b66d-2f42-4897-8803-ad831eb29045.pdf"},{"id":88292987,"identity":"047062f1-f53e-46af-a51a-ec8a4c56971c","added_by":"auto","created_at":"2025-08-05 02:45:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":55961472,"visible":true,"origin":"","legend":"Dissecting Tissue Architecture and Function through Mapping of Cellular Communication Networks","description":"","filename":"Supplementary0618.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6920553/v1/148fb50f510511d2506a14e0.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Dissecting Tissue Architecture and Function through Mapping of Cellular Communication Networks","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"cellular communication network, Poisson graphical model, scan, hotspot","lastPublishedDoi":"10.21203/rs.3.rs-6920553/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6920553/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Spatial transcriptome provides critical insights for inferring cell-cell communications. Based on the heuristic that physically adjacent cells are more likely to communicate with each other, we develop a computational framework that Infers the Cell-Cell Communication network (IC3) and subsequently identifies communication hotspots with rigorous error control. We demonstrate in simulations and real datasets that our method outperforms existing methods in accuracy and especially improves sensitivity to identify communications involving rare cell types. Applying IC3 in a mouse brain dataset, we recovered how cells communicate with each other to form a local structure that regulates the balance of the blood-brain barrier. These findings highlight that our method is effective in revealing tissue architecture and function from cellular communication networks.","manuscriptTitle":"Dissecting Tissue Architecture and Function through Mapping of Cellular Communication Networks","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-05 02:45:48","doi":"10.21203/rs.3.rs-6920553/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":"4c76d05e-755d-4b1b-a7c1-21ef95cd8b2d","owner":[],"postedDate":"August 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":50583728,"name":"Biological sciences/Computational biology and bioinformatics/Cellular signalling networks"},{"id":50583729,"name":"Biological sciences/Neuroscience/Cellular neuroscience"},{"id":50583730,"name":"Biological sciences/Biotechnology/Genomics/Transcriptomics"}],"tags":[],"updatedAt":"2025-08-05T02:45:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-05 02:45:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6920553","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6920553","identity":"rs-6920553","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.