The Quantified Immune-Aging Dysregulation Index (TENSE): a Large-Language Model-powered method to annotate and quantify systems-level dysregulation

The Quantified Immune-Aging Dysregulation Index (TENSE): a Large-Language Model-powered method to annotate and quantify systems-level dysregulation | 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 Method Article The Quantified Immune-Aging Dysregulation Index (TENSE): a Large-Language Model-powered method to annotate and quantify systems-level dysregulation George Vavougios, Georgios Hadjigeorgiou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7377143/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract In this work, we present an alternative method of annotating pathway enrichment data to extract knowledge on dysregulation and disease-associated processes. Rather than focus on hypothesis-driven or arbitrarily selected pathways, we attempt a synthetic approach via the definition of the TENSE (quanTifiEd immuNe-aging dySregulation index) scoring scheme as a measure of relative immune-derived age-related disorder. TENSE and DIRES is an AI-powered workflow that quantifies systems-level dysregulation in disease, with an intended focus on neurological conditions. We provide several use cases that display the utility the TENSE and the DIRES scoring scheme in three use cases (Alzheimer’s disease, exposure to ionizing radiation, treatment with vorinostat) and examine the biological insight gained by its application. In each case, TENSE and DIRES produce replicable and consistent insight that provides an alternative to arbitrary interpretation of biological pathways, as well as quantified metrics on the involvement of major age-related processes in each studied condition. Cellular & Molecular Neuroscience Neurology Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted 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-7377143","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Method Article","associatedPublications":[],"authors":[{"id":500753170,"identity":"2c6553b8-23a5-49ea-a03f-468b721246fc","order_by":0,"name":"George Vavougios","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYDCCA6hsmwQwK6EArxbGBiQtaQkMbCAtBkRqAYLDEC0MeLTwHT97/MHHNrvEfon0iwc+/Dmfxy/fnfjhgQGDPL/YAaxaJM/kJTbObEtOnDkjp+DgzLbbxZJtvJslgA4znDk7AasWgwM5hs08Z5iNDW7kJBzmbbiduOEY7waQlgSD2zi0nH9j2PznTD1EC8+fcyAtm3/g1XIDaAtDxWE5gxvpBw7zsB0AadmG1xbJG28MZ/ZUHJeT7HnDcBDsqbbcbRYJBhI4/cJ3Psfgww+Dah5+9vTHHz78AQYd89nNN39U2MjzS2PXggR4UOJCgpByEGB/QIyqUTAKRsEoGIEAADlLakiYaiC2AAAAAElFTkSuQmCC","orcid":"","institution":"University of Cyprus","correspondingAuthor":true,"prefix":"","firstName":"George","middleName":"","lastName":"Vavougios","suffix":""},{"id":500753171,"identity":"af41c234-be7a-442f-8e02-f503fec882ae","order_by":1,"name":"Georgios Hadjigeorgiou","email":"","orcid":"","institution":"University of Cyprus","correspondingAuthor":false,"prefix":"","firstName":"Georgios","middleName":"","lastName":"Hadjigeorgiou","suffix":""}],"badges":[],"createdAt":"2025-08-14 23:01:10","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7377143/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7377143/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89278648,"identity":"7d760d48-c7d6-4301-8a50-9b3d338b201b","added_by":"auto","created_at":"2025-08-18 10:01:15","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":529302,"visible":true,"origin":"","legend":"","description":"","filename":"InflammagingIndexMethodsManuscriptv1.5a.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7377143/v1_covered_7527e9ca-b6bd-458d-8b1c-84a07bdf648d.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eThe Quantified Immune-Aging Dysregulation Index (TENSE): a Large-Language Model-powered method to annotate and quantify systems-level dysregulation\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7377143/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7377143/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn this work, we present an alternative method of annotating pathway enrichment data to extract knowledge on dysregulation and disease-associated processes. Rather than focus on hypothesis-driven or arbitrarily selected pathways, we attempt a synthetic approach via the definition of the TENSE (quanTifiEd immuNe-aging dySregulation index) scoring scheme as a measure of relative immune-derived age-related disorder. TENSE and DIRES is an AI-powered workflow that quantifies systems-level dysregulation in disease, with an intended focus on neurological conditions. We provide several use cases that display the utility the TENSE and the DIRES scoring scheme in three use cases (Alzheimer’s disease, exposure to ionizing radiation, treatment with vorinostat) and examine the biological insight gained by its application. In each case, TENSE and DIRES produce replicable and consistent insight that provides an alternative to arbitrary interpretation of biological pathways, as well as quantified metrics on the involvement of major age-related processes in each studied condition.\u003c/p\u003e","manuscriptTitle":"The Quantified Immune-Aging Dysregulation Index (TENSE): a Large-Language Model-powered method to annotate and quantify systems-level dysregulation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-18 09:37:09","doi":"10.21203/rs.3.rs-7377143/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2fbfc7df-02a6-41f8-bafc-9be97c347d33","owner":[],"postedDate":"August 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":53199025,"name":"Cellular \u0026 Molecular Neuroscience"},{"id":53199026,"name":"Neurology"}],"tags":[],"updatedAt":"2025-08-18T09:37:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-18 09:37:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7377143","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7377143","identity":"rs-7377143","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}