A general and extensible algorithmic framework for biological sequence alignment across scales and applications

A general and extensible algorithmic framework for biological sequence alignment across scales and applications | 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 A general and extensible algorithmic framework for biological sequence alignment across scales and applications Cuncong Zhong, Hao Xuan, Hongyang Sun, Xiangtao Liu, Hanyuan Zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9304575/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 Sequence alignment underlies nearly every facet of modern genomics, from genetic testing and cancer profiling to functional genome annotation. Yet, despite decades of algorithmic innovation, most existing aligners remain narrowly optimized for specific tasks, leading to fragmented analytical workflows. Here, we introduce the Versatile Alignment Toolkit (VAT), a unified algorithmic framework that brings together diverse seeding and genome-indexing strategies within a single, modulated architecture. VAT features a novel multi-view k-mer indexing scheme that integrates multiple seeding strategies, while enabling run-time adjustment of seed length without re-indexing. A hardware-efficient bitonic sort algorithm accelerates multi-view table construction, ensuring scalability across large datasets. VAT delivers consistently high alignment quality and efficiency across a wide range of alignment tasks, including short- and long-read mapping, homology search, and whole-genome alignment. By bridging alignment paradigms that were previously treated in isolation, VAT reduces workflow complexity and establishes an extensible foundation for future sequencing technologies. Biological sciences/Computational biology and bioinformatics/Sequence annotation Biological sciences/Computational biology and bioinformatics/Software Biological sciences/Computational biology and bioinformatics/Genome informatics short-read mapping long-read mapping homology search whole-genome alignment Full Text Additional Declarations Yes there is potential Competing Interest. Authors HX, JZ, and CZ hold equity interests in H2Alpha Inc., a company developing technologies related to the subject of this study. This relationship had no role in the study design, data collection, analysis, interpretation, or manuscript preparation. All other authors declare that they have no competing interests. Supplementary Files SupplementaryMaterialV10.pdf Supplementary Materials 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-9304575","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":632774792,"identity":"6fe03c24-e53c-4d2c-a728-4ae004b63552","order_by":0,"name":"Cuncong Zhong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYHACNhAhJwEieUjRYky6lsQZRGvhbz/+7MHHHbXpM2ckMD5420aEFokzCemGM88cz50tkcBsOJcYLQYSDMekeduO5c6TSGADMojSwtgG0pIuJ5HA/ptILcwgw2sSpIG2MBOlReJMGpvkzLYDhjN7HjZLzjlHhBZQiEl8bKuTlziefPDDmzIitEDBYSBmbCBePRDUkaR6FIyCUTAKRhgAAAp1MMj1EsnUAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-8777-082X","institution":"University of Kansas","correspondingAuthor":true,"prefix":"","firstName":"Cuncong","middleName":"","lastName":"Zhong","suffix":""},{"id":632774794,"identity":"9d8734ea-1afe-425c-a6ff-48edef0b489a","order_by":1,"name":"Hao Xuan","email":"","orcid":"","institution":"University of Kansas","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Xuan","suffix":""},{"id":632774795,"identity":"52a64d51-6a9b-4962-a5bb-5830349783ea","order_by":2,"name":"Hongyang Sun","email":"","orcid":"","institution":"University of Kansas","correspondingAuthor":false,"prefix":"","firstName":"Hongyang","middleName":"","lastName":"Sun","suffix":""},{"id":632774797,"identity":"35202c38-b048-4239-badb-ab8f6d931dbc","order_by":3,"name":"Xiangtao Liu","email":"","orcid":"","institution":"Guangzhou Vocational University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Xiangtao","middleName":"","lastName":"Liu","suffix":""},{"id":632774798,"identity":"376f5aae-deec-480b-9479-5a2c1d0f9f4b","order_by":4,"name":"Hanyuan Zhang","email":"","orcid":"","institution":"Xinjiang Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hanyuan","middleName":"","lastName":"Zhang","suffix":""},{"id":632774799,"identity":"6773bc4d-528d-4d59-8aa5-d6848087fe0b","order_by":5,"name":"Jun Zhang","email":"","orcid":"","institution":"OSF Healthcare Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2026-04-02 14:52:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9304575/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9304575/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109249521,"identity":"e6762ef0-5d00-4fa6-ac3d-05e8f5fbad64","added_by":"auto","created_at":"2026-05-14 08:55:09","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1036737,"visible":true,"origin":"","legend":"Article File","description":"","filename":"VATNMManuscriptV10.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9304575/v1_covered_97f6ea4c-02da-4325-9e22-536e43587ce6.pdf"},{"id":109231756,"identity":"57d6fafc-616d-4fe5-a080-1fe1d865db90","added_by":"auto","created_at":"2026-05-14 03:27:42","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1979976,"visible":true,"origin":"","legend":"Supplementary Materials","description":"","filename":"SupplementaryMaterialV10.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9304575/v1/1e92c29e8949fdbef8d200e0.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nAuthors HX, JZ, and CZ hold equity interests in H2Alpha Inc., a company developing technologies related to the subject of this study. 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