Lossless Pangenome Indexing Using Tag Arrays

Lossless Pangenome Indexing Using Tag Arrays | 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 Lossless Pangenome Indexing Using Tag Arrays Parsa Eskandar, Benedict Paten, Jouni Sirén This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8233501/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Pangenome graphs represent the genomic variation by encoding multiple haplotypes within a unified graph structure. However, efficient and lossless indexing of such structures remains challenging due to the scale and complexity of pangenomic data. We present a practical and scalable indexing framework based on tag arrays, which annotate positions in the Burrows--Wheeler transform (BWT) with graph coordinates. Our method extends the FM-index with a run-length compressed tag structure that enables efficient retrieval of all unique graph locations where a query pattern appears. We introduce a novel construction algorithm that combines unique $k$-mers, graph-based extensions, and haplotype traversal to compute the tag array in a memory-efficient manner. To support large genomes, we process each chromosome independently and then merge the results into a unified index using properties of the multi-string BWT and r-index. Our evaluation on the HPRC graphs demonstrates that the tag array structure compresses effectively, scales well with added haplotypes, and preserves accurate mapping information across diverse regions of the genome. This indexing method enables lossless and haplotype-aware querying in complex pangenomes and offers a practical indexing layer to develop scalable aligners and downstream graph-based analysis tools. The index additionally supports efficient one-to-all coordinate translation, enabling any interval on a haplotype to be mapped to its corresponding intervals across all other haplotypes in the graph. pangenome indexing Burrows–Wheeler transform tag arrays Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 30 Apr, 2026 Reviews received at journal 04 Feb, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers invited by journal 13 Jan, 2026 Editor assigned by journal 02 Dec, 2025 Submission checks completed at journal 01 Dec, 2025 First submitted to journal 28 Nov, 2025 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-8233501","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":574260090,"identity":"66d5bbfb-d193-4c6f-bda6-7a114a52eaa0","order_by":0,"name":"Parsa Eskandar","email":"","orcid":"","institution":"University of California, Santa Cruz","correspondingAuthor":false,"prefix":"","firstName":"Parsa","middleName":"","lastName":"Eskandar","suffix":""},{"id":574260091,"identity":"aaccefb0-1c49-4b18-ae5f-11bebf88eeab","order_by":1,"name":"Benedict Paten","email":"","orcid":"","institution":"University of California, Santa Cruz","correspondingAuthor":false,"prefix":"","firstName":"Benedict","middleName":"","lastName":"Paten","suffix":""},{"id":574260092,"identity":"2c6a103d-9416-44e3-a0f0-2d20bde5022a","order_by":2,"name":"Jouni Sirén","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAu0lEQVRIiWNgGAWjYBACxnYGhgNAWg7KZyZCSzNEizHxWmBqEhuI1sLczP7wcEXFnfQNx48//MBQYQ3Ti89hPAYHz5x5lrvhTI6xBMOZdKK0MBxsbDucu+EGDxsDY9thYrSwPzjY+O9wusEN9mcMjP+I0sJgcLCx4XCCwQ0GMwbGBqK0AP3ScOyw4UyQXxKOpRsT1GLY3v74Y0PNYXk+UIh9qLGWJawFRUUCIeUgIE+MolEwCkbBKBjhAACfPUIkMBzvgwAAAABJRU5ErkJggg==","orcid":"","institution":"University of California, Santa Cruz","correspondingAuthor":true,"prefix":"","firstName":"Jouni","middleName":"","lastName":"Sirén","suffix":""}],"badges":[],"createdAt":"2025-11-28 23:08:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8233501/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8233501/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100497152,"identity":"1db905f7-7d75-45ef-bcd8-dad1395b4968","added_by":"auto","created_at":"2026-01-18 04:07:42","extension":"json","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":5161,"visible":true,"origin":"","legend":"","description":"","filename":"acc7f834b93241e982199fc453ca5c40.json","url":"https://assets-eu.researchsquare.com/files/rs-8233501/v1/399e3aa73f74e55cd6a89a4a.json"},{"id":100548149,"identity":"5a1d711c-45f6-409a-868c-448bae680576","added_by":"auto","created_at":"2026-01-19 08:17:39","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":767676,"visible":true,"origin":"","legend":"","description":"","filename":"TagArrayIndexingExtended.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8233501/v1_covered_09543b32-5345-4f6e-bdfb-fad4bb76ff89.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lossless Pangenome Indexing Using Tag Arrays","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":"algorithms-for-molecular-biology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"amob","sideBox":"Learn more about [Algorithms for Molecular Biology](http://almob.biomedcentral.com/)","snPcode":"13015","submissionUrl":"https://submission.nature.com/new-submission/13015/3","title":"Algorithms for Molecular Biology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"pangenome indexing, Burrows–Wheeler transform, tag arrays","lastPublishedDoi":"10.21203/rs.3.rs-8233501/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8233501/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Pangenome graphs represent the genomic variation by encoding multiple haplotypes within a unified graph structure. 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