A codon usage-based approach for the stratification of Influenza A

A codon usage-based approach for the stratification of Influenza A | 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 A codon usage-based approach for the stratification of Influenza A Tommaso Alfonsi, Matteo Chiara, Anna Bernasconi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5737660/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Jun, 2025 Read the published version in Computational and Structural Biotechnology Journal → Version 1 posted You are reading this latest preprint version Abstract Background: Influenza A virus (IAV) is a highly adaptable pathogen that poses a significant threat to human health. Genomic surveillance of IAVs is a complex task due to its broad host range, its zoonotic potential, and rapid evolution. Strategies based on codon preference analysis have been successfully employed for the categorization of IAVs with different host specificity in the past. Hence, monitoring codon usage adaptation, where viral codon preferences align with host preferences to enhance replication efficiency, offers a promising strategy for tracking IAV and identifying significant epidemiological events. Results: In this study, we develop a computational workflow for the analysis and stratification of IAVs based on codon usage profiles across large datasets. Using three key case studies--the 2009 H1N1 pandemic, the H7N9 epidemic in China (2013–2017), and the long-term circulation of H5N1 in domestic birds--we demonstrate the applicability of codon usage metrics for capturing patterns of viral adaptation and genomic diversification. Our approach uncovered interesting genomic features, which are not always reflected by the clade-based nomenclature. Interestingly a reduced set of amino acids and associated codons was sufficient to summarize salient patterns of IAV genomes, suggesting shared evolutionary pressures across IAV serotypes. Conclusion: Codon usage-based stratification effectively highlighted key epidemiological events and enabled detailed comparisons of genomic features across IAV serotypes. This approach provides a scalable framework for IAV genomic surveillance, offering insights into viral evolution and adaptation. Its general applicability makes it suitable for extending to other Influenza A serotypes, particularly those for which available genomic data are limited or a reference nomenclature is not established. Influenza A Virus Codon Usage Adaptation Genomic Surveillance Viral Evolution and Adaptation Epidemiological Events Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryFile.pdf Cite Share Download PDF Status: Published Journal Publication published 24 Jun, 2025 Read the published version in Computational and Structural Biotechnology Journal → 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-5737660","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":403587256,"identity":"9cfb8189-4c0f-41e5-b85d-c66cb4023fdb","order_by":0,"name":"Tommaso Alfonsi","email":"","orcid":"","institution":"Politecnico di Milano","correspondingAuthor":false,"prefix":"","firstName":"Tommaso","middleName":"","lastName":"Alfonsi","suffix":""},{"id":403587257,"identity":"57bbc950-7cf4-4b21-95cb-03514b6b6411","order_by":1,"name":"Matteo Chiara","email":"","orcid":"","institution":"University of Milan","correspondingAuthor":false,"prefix":"","firstName":"Matteo","middleName":"","lastName":"Chiara","suffix":""},{"id":403587258,"identity":"a5df50c8-7ae6-4154-aed1-089dcf8b4a39","order_by":2,"name":"Anna Bernasconi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYLACxgY4U0KOgYG54QCDAQMP0VqMQVywFrx6kLQwJDbAuLi08M/uPfiBcYdNvjn78YcfPu6wSN/O3th46EYBg4w9Di0Sd84lSzCeSbPc2ZNjLDnzjETuzp6DDYdz8DnsRo6BBGPbYQODAzlszLxtErkbbiTi1yJ/I8f4B2PbfwOD88+fgbSkGxDSYnAjxwxoywEDgxsJZiAtCQS1GAK1WCSeSQZqeQP0S5uEIdQvEjw8B7BrkQM67MbHHXZAh6UDQ6ytTt6cvfnw55w/NvbsDbj8DwQJKE6FUBJ41GP4jgS1o2AUjIJRMDIAAP1eWWxC5/EjAAAAAElFTkSuQmCC","orcid":"","institution":"Politecnico di Milano","correspondingAuthor":true,"prefix":"","firstName":"Anna","middleName":"","lastName":"Bernasconi","suffix":""}],"badges":[],"createdAt":"2024-12-30 19:53:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5737660/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5737660/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1016/j.csbj.2025.06.030","type":"published","date":"2025-06-25T00:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":85697368,"identity":"2e27bdd2-b3c4-4dbd-a3c3-63a38541b8e3","added_by":"auto","created_at":"2025-06-30 18:57:00","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1607836,"visible":true,"origin":"","legend":"","description":"","filename":"Archive.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5737660/v1_covered_8765513c-199f-4fe9-87dd-0b7febbd4e5e.pdf"},{"id":74631076,"identity":"7eeda505-da35-4391-b7a5-406c4b9e2c76","added_by":"auto","created_at":"2025-01-24 07:48:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1986162,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFile.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5737660/v1/08335229f99df17a7d7942de.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A codon usage-based approach for the stratification of Influenza A","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"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":"Influenza A Virus, Codon Usage Adaptation, Genomic Surveillance, Viral Evolution and Adaptation, Epidemiological Events","lastPublishedDoi":"10.21203/rs.3.rs-5737660/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5737660/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Influenza A virus (IAV) is a highly adaptable pathogen that poses a significant threat to human health. Genomic surveillance of IAVs is a complex task due to its broad host range, its zoonotic potential, and rapid evolution. Strategies based on codon preference analysis have been successfully employed for the categorization of IAVs with different host specificity in the past. Hence, monitoring codon usage adaptation, where viral codon preferences align with host preferences to enhance replication efficiency, offers a promising strategy for tracking IAV and identifying significant epidemiological events.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults: In this study, we develop a computational workflow for the analysis and stratification of IAVs based on codon usage profiles across large datasets. Using three key case studies--the 2009 H1N1 pandemic, the H7N9 epidemic in China (2013–2017), and the long-term circulation of H5N1 in domestic birds--we demonstrate the applicability of codon usage metrics for capturing patterns of viral adaptation and genomic diversification. Our approach uncovered interesting genomic features, which are not always reflected by the clade-based nomenclature. Interestingly a reduced set of amino acids and associated codons was sufficient to summarize salient patterns of IAV genomes, suggesting shared evolutionary pressures across IAV serotypes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusion: Codon usage-based stratification effectively highlighted key epidemiological events and enabled detailed comparisons of genomic features across IAV serotypes. This approach provides a scalable framework for IAV genomic surveillance, offering insights into viral evolution and adaptation. Its general applicability makes it suitable for extending to other Influenza A serotypes, particularly those for which available genomic data are limited or a reference nomenclature is not established.\u003c/p\u003e","manuscriptTitle":"A codon usage-based approach for the stratification of Influenza A","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-24 07:48:04","doi":"10.21203/rs.3.rs-5737660/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":"bb653f70-5e29-436c-a625-061028cbe96b","owner":[],"postedDate":"January 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-30T18:56:53+00:00","versionOfRecord":{"articleIdentity":"rs-5737660","link":"https://doi.org/10.1016/j.csbj.2025.06.030","journal":{"identity":"computational-and-structural-biotechnology-journal","isVorOnly":true,"title":"Computational and Structural Biotechnology Journal"},"publishedOn":"2025-06-25 00:00:00","publishedOnDateReadable":"June 25th, 2025"},"versionCreatedAt":"2025-01-24 07:48:04","video":"","vorDoi":"10.1016/j.csbj.2025.06.030","vorDoiUrl":"https://doi.org/10.1016/j.csbj.2025.06.030","workflowStages":[]},"version":"v1","identity":"rs-5737660","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5737660","identity":"rs-5737660","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}