Identification of Macrophage-Related Biomarkers for Abdominal Aortic Aneurysm through Combined Single-Cell Sequencing and Machine Learning

Identification of Macrophage-Related Biomarkers for Abdominal Aortic Aneurysm through Combined Single-Cell Sequencing and Machine Learning | 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 Research Article Identification of Macrophage-Related Biomarkers for Abdominal Aortic Aneurysm through Combined Single-Cell Sequencing and Machine Learning Guoqing Yao, Xuemei Hu, Daqiang Song, Jin Yao, Deqing Chen, Tiankuo Luan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4977816/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 The relationship between macrophages and the progression of abdominal aortic aneurysms (AAA) remains unclear, and effective biomarkers are lacking. In this study, we elucidate the mechanism by which macrophages promote AAA development and identify associated biomarkers, with the goal of developing new targeted therapies and improving patient outcomes. Differential expression analysis, weighted gene co-expression network analysis, and single-cell analysis were used to identify macrophage-related genes in an AAA dataset. Machine learning algorithms identified THBS1, HCLS1, DMXL2, and ZEB2 as key macrophage-related genes upregulated in AAA; these four hub genes were then used to construct a nomogram as an auxiliary tool for clinical diagnosis. Subsequent downstream single-cell and CellChat analyses were conducted to observe the interactions between macrophages and fibroblasts and analyze potential pathways. Single-cell validation confirmed enhanced THBS1 expression in macrophages within AAA. CellChat analysis revealed enhanced interaction between macrophages and fibroblasts in AAA through THBS1–CD47 signaling. Finally, clinical samples from patients with AAA confirmed the high expression of THBS1 and CD47 in AAA. Our findings highlight THBS1 as a potential driver of macrophage-mediated AAA formation and an important biomarker for AAA diagnosis. Abdominal aortic aneurysm Macrophage Single-cell sequencing Machine learning algorithm CellChat. Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterial.pdf 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-4977816","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":345760905,"identity":"9f007327-d05a-4006-ba8f-d1b25bc31b81","order_by":0,"name":"Guoqing Yao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIiWNgGAWjYBADHgYG5gNIfDaitLAlMCA0EaEFpMuAOC0Gxw8ffs1TYS1jzr/m8+ePbQzyfNfOGDB8KDvMwD+7AbuWM2lp1jxn0nksZ7zdJnGwjcFw5u0cA8YZ5w4zSNw5gF3LgRwzY962wzwGN85uYwBqSTAAamEGijAYSCRg13L+DUzLmccf4Fr+4tNyI8f4MVjL+R4GCbgWRjxaJG88S2OcA/SLwQ02M4kz5ySAfkkrONhzLp1H4gZ2LXznkw9/eFNhbW9w/vDjDxVlNvJ8t5M3PvhRZi3HPwO7FoUDDGwSwJhnYIA4A8g+AEagyMUO5BsYmD+AtfAfgAodwKV2FIyCUTAKRioAAJt1ZL64YxxwAAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Chongqing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Guoqing","middleName":"","lastName":"Yao","suffix":""},{"id":345760906,"identity":"e2b45314-315e-4593-ba80-616fdfc7d8db","order_by":1,"name":"Xuemei Hu","email":"","orcid":"","institution":"The People's Hospital of Rongchang District","correspondingAuthor":false,"prefix":"","firstName":"Xuemei","middleName":"","lastName":"Hu","suffix":""},{"id":345760908,"identity":"3fd86a43-8e51-4d50-b01d-5273689d2506","order_by":2,"name":"Daqiang Song","email":"","orcid":"","institution":"The First Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Daqiang","middleName":"","lastName":"Song","suffix":""},{"id":345760909,"identity":"a006a9ac-4f52-4ae1-a183-cfe0ee63e570","order_by":3,"name":"Jin Yao","email":"","orcid":"","institution":"Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jin","middleName":"","lastName":"Yao","suffix":""},{"id":345760911,"identity":"7f294020-d115-4eba-a479-c4e60d33b24b","order_by":4,"name":"Deqing Chen","email":"","orcid":"","institution":"The People's Hospital of Rongchang District","correspondingAuthor":false,"prefix":"","firstName":"Deqing","middleName":"","lastName":"Chen","suffix":""},{"id":345760912,"identity":"82b26cd5-1368-4ff3-82b3-53c914437b4b","order_by":5,"name":"Tiankuo Luan","email":"","orcid":"","institution":"Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tiankuo","middleName":"","lastName":"Luan","suffix":""},{"id":345760913,"identity":"d22f015d-749d-4ca7-824d-feeafda2512e","order_by":6,"name":"Yu Zhao","email":"","orcid":"","institution":"The First Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Zhao","suffix":""}],"badges":[],"createdAt":"2024-08-26 12:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4977816/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4977816/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":65133609,"identity":"78574a9d-f42b-45aa-af68-914f8478a2c1","added_by":"auto","created_at":"2024-09-24 03:20:52","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1560930,"visible":true,"origin":"","legend":"","description":"","filename":"Article.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4977816/v1_covered_f248e366-fd0a-411f-9d6a-acaf3ea1f81f.pdf"},{"id":65132357,"identity":"57f3ad33-b402-43b4-a906-cd630e3c5de0","added_by":"auto","created_at":"2024-09-24 02:56:45","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1410191,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4977816/v1/58ae05a4f62aae4656deb814.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Identification of Macrophage-Related Biomarkers for Abdominal Aortic Aneurysm through Combined Single-Cell Sequencing and Machine Learning","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":"Abdominal aortic aneurysm, Macrophage, Single-cell sequencing, Machine learning algorithm, CellChat.","lastPublishedDoi":"10.21203/rs.3.rs-4977816/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4977816/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The relationship between macrophages and the progression of abdominal aortic aneurysms (AAA) remains unclear, and effective biomarkers are lacking. In this study, we elucidate the mechanism by which macrophages promote AAA development and identify associated biomarkers, with the goal of developing new targeted therapies and improving patient outcomes. Differential expression analysis, weighted gene co-expression network analysis, and single-cell analysis were used to identify macrophage-related genes in an AAA dataset. Machine learning algorithms identified THBS1, HCLS1, DMXL2, and ZEB2 as key macrophage-related genes upregulated in AAA; these four hub genes were then used to construct a nomogram as an auxiliary tool for clinical diagnosis. Subsequent downstream single-cell and CellChat analyses were conducted to observe the interactions between macrophages and fibroblasts and analyze potential pathways. Single-cell validation confirmed enhanced THBS1 expression in macrophages within AAA. CellChat analysis revealed enhanced interaction between macrophages and fibroblasts in AAA through THBS1–CD47 signaling. Finally, clinical samples from patients with AAA confirmed the high expression of THBS1 and CD47 in AAA. Our findings highlight THBS1 as a potential driver of macrophage-mediated AAA formation and an important biomarker for AAA diagnosis.","manuscriptTitle":"Identification of Macrophage-Related Biomarkers for Abdominal Aortic Aneurysm through Combined Single-Cell Sequencing and Machine Learning","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-24 02:56:40","doi":"10.21203/rs.3.rs-4977816/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":"7c44e9cc-eb01-4510-be6a-1a034d7dbe86","owner":[],"postedDate":"September 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-24T02:56:42+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-24 02:56:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4977816","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4977816","identity":"rs-4977816","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}