{"paper_id":"02f65b3b-a071-4d13-aa91-7919363fde89","body_text":"Rapid, accurate long- and short-read mapping to large pangenome graphs with vg Giraffe | 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 Rapid, accurate long- and short-read mapping to large pangenome graphs with vg Giraffe Benedict Paten, Xian Chang, Adam Novak, Jordan Eizenga, Jouni Sirén, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7747403/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 We previously introduced Giraffe, a short-read-to-pangenome graph mapper available in the vg pangenomics toolkit. Giraffe was fast and accurate for mapping short reads to human-scale pangenomes, but struggled with long reads. Long reads present a unique challenge to pangenome mapping algorithms due to their length and error profile, which allow them to take more topologically complex paths through the pangenome graph and increase the possible search space for the algorithm. We present updates to Giraffe that allow it to quickly and accurately map long reads to pangenome graphs. For both short and long reads, Giraffe mapping to a pangenome containing data from more than 450 human haplotypes, generated by the Human Pangenome Reference Consortium, is comparable in speed to linear mappers to human reference genomes; Giraffe is also over an order of magnitude faster than GraphAligner, the current state-of-the-art long-read-to-pangenome mapper. Its alignments produce similar or improved small and structural variant calling results, compared to those from commonly used graph-based and linear mappers. We additionally demonstrate using Giraffe's long read alignments in a pangenome-guided assembly workflow, which is capable of producing more contiguous local assemblies than Hifiasm in our test regions. Biological sciences/Computational biology and bioinformatics/Genome informatics Biological sciences/Genetics Full Text Additional Declarations Yes there is potential Competing Interest. A.C., K.S., and P.-C.C. are employees of Google and own Alphabet stock as part of the standard compensation package. The remaining authors declare no competing interests. Supplementary Files longreadgiraffesupplement.pdf Supplementary Material Authorsalsoputtogetheralittlegiraffedemoonthewikithatcanberunonalaptop.docx Author also put together a little giraffe demo on the wiki that can be run on a laptop 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-7747403\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":533233400,\"identity\":\"d4f5f96f-40f4-4459-a0de-2f5ca3b835ff\",\"order_by\":0,\"name\":\"Benedict 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