{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:27:16Z","timestamp":1776054436603,"version":"3.50.1"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Structural variants (SVs) play an important role in evolutionary and functional genomics but are challenging to characterize. High-accuracy, long-read sequencing can substantially improve SV characterization when coupled with effective calling methods. While state-of-the-art long-read SV callers are highly accurate, further improvements are achievable by systematically modeling local haplotypes during SV discovery and genotyping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We describe sawfish, an SV caller for mapped high-quality long reads incorporating systematic SV haplotype modeling to improve accuracy and resolution. Assessment against the draft Genome in a Bottle (GIAB) SV benchmark from the T2T-HG002-Q100 diploid assembly shows that sawfish has the highest accuracy among state-of-the-art long-read SV callers across every tested SV size group. Additionally, sawfish maintains the highest accuracy at every tested depth level from 10- to 32-fold coverage, such that other callers required at least 30-fold coverage to match sawfish accuracy at 15-fold coverage. Sawfish also shows the highest accuracy in the GIAB challenging medically relevant genes benchmark, demonstrating improvements in both comprehensive and medically relevant contexts.<\/jats:p>\n                    <jats:p>When joint-genotyping seven samples from CEPH-1463, sawfish has over 9000 more pedigree-concordant calls than other state-of-the-art SV callers, with the highest proportion of concordant SVs (81%). Sawfish\u2019s quality model enables selection for an even higher proportion of concordant SVs (88%), while still calling nearly 5000 more pedigree-concordant SVs than other callers. These results demonstrate that sawfish improves on the state-of-the-art for long-read SV calling accuracy across both individual and joint-sample analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>Sawfish source code, pre-compiled Linux binaries, and documentation are released on GitHub: https:\/\/github.com\/PacificBiosciences\/sawfish.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf136","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T09:59:21Z","timestamp":1744106361000},"source":"Crossref","is-referenced-by-count":23,"title":["Sawfish: improving long-read structural variant discovery and genotyping with local haplotype modeling"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0726-7600","authenticated-orcid":false,"given":"Christopher T","family":"Saunders","sequence":"first","affiliation":[{"name":"Computational Biology, PacBio , Menlo Park, CA 94025,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6411-9236","authenticated-orcid":false,"given":"James M","family":"Holt","sequence":"additional","affiliation":[{"name":"Computational Biology, PacBio , Menlo Park, CA 94025,","place":["United States"]}]},{"given":"Daniel N","family":"Baker","sequence":"additional","affiliation":[{"name":"Computational Biology, PacBio , Menlo Park, CA 94025,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-5645","authenticated-orcid":false,"given":"Juniper A","family":"Lake","sequence":"additional","affiliation":[{"name":"Computational Biology, PacBio , Menlo Park, CA 94025,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5470-8299","authenticated-orcid":false,"given":"Jonathan R","family":"Belyeu","sequence":"additional","affiliation":[{"name":"Computational Biology, PacBio , Menlo Park, CA 94025,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7627-9808","authenticated-orcid":false,"given":"Zev","family":"Kronenberg","sequence":"additional","affiliation":[{"name":"Computational Biology, PacBio , Menlo Park, CA 94025,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7422-1194","authenticated-orcid":false,"given":"William J","family":"Rowell","sequence":"additional","affiliation":[{"name":"Computational Biology, PacBio , Menlo Park, CA 94025,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8965-1253","authenticated-orcid":false,"given":"Michael A","family":"Eberle","sequence":"additional","affiliation":[{"name":"Computational Biology, PacBio , Menlo Park, CA 94025,","place":["United States"]}]}],"member":"286","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"2025041602170845900_btaf136-B1","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1038\/s41467-018-08148-z","article-title":"Multi-platform discovery of haplotype-resolved structural variation in human genomes","volume":"10","author":"Chaisson","year":"2019","journal-title":"Nat Commun"},{"key":"2025041602170845900_btaf136-B2","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41592-020-01056-5","article-title":"Haplotype-resolved de novo assembly using phased assembly graphs with hifiasm","volume":"18","author":"Cheng","year":"2021","journal-title":"Nat Methods"},{"key":"2025041602170845900_btaf136-B3","doi-asserted-by":"crossref","DOI":"10.1126\/science.abf7117","article-title":"Haplotype-resolved diverse human genomes and integrated analysis of structural variation","volume":"372","author":"Ebert","year":"2021","journal-title":"Science"},{"key":"2025041602170845900_btaf136-B4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1186\/s13059-022-02840-6","article-title":"Truvari: refined structural variant comparison preserves allelic diversity","volume":"23","author":"English","year":"2022","journal-title":"Genome Biol"},{"key":"2025041602170845900_btaf136-B5","author":"Kronenberg","year":"2024"},{"key":"2025041602170845900_btaf136-B6","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41576-020-0236-x","article-title":"Long-read human genome sequencing and its applications","volume":"21","author":"Logsdon","year":"2020","journal-title":"Nat Rev Genet"},{"key":"2025041602170845900_btaf136-B7","doi-asserted-by":"publisher","author":"Porubsky","year":"2024.","DOI":"10.1038\/s41586-025-08922-2"},{"key":"2025041602170845900_btaf136-B8","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1038\/s41587-024-02141-2","article-title":"Detection of mosaic and population-level structural variants with Sniffles2","volume":"42","author":"Smolka","year":"2024","journal-title":"Nat Biotechnol"},{"key":"2025041602170845900_btaf136-B9","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nature15394","article-title":"An integrated map of structural variation in 2,504 human genomes","volume":"526","author":"Sudmant","year":"2015","journal-title":"Nature"},{"key":"2025041602170845900_btaf136-B10"},{"key":"2025041602170845900_btaf136-B11","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s41587-021-01158-1","article-title":"Curated variation benchmarks for challenging medically relevant autosomal genes","volume":"40","author":"Wagner","year":"2022","journal-title":"Nat Biotechnol"},{"key":"2025041602170845900_btaf136-B12","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/s41587-019-0217-9","article-title":"Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome","volume":"37","author":"Wenger","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2025041602170845900_btaf136-B13","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.ajhg.2021.03.014","article-title":"Expectations and blind spots for structural variation detection from long-read assemblies and short-read genome sequencing technologies","volume":"108","author":"Zhao","year":"2021","journal-title":"Am J Hum Genet"},{"key":"2025041602170845900_btaf136-B14","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1038\/s41587-020-0538-8","article-title":"A robust benchmark for detection of germline large deletions and insertions","volume":"38","author":"Zook","year":"2020","journal-title":"Nat Biotechnol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaf136\/62899142\/btaf136.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/4\/btaf136\/62899142\/btaf136.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/4\/btaf136\/62899142\/btaf136.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T02:17:26Z","timestamp":1744769846000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btaf136\/8109432"}},"subtitle":[],"editor":[{"given":"Peter","family":"Robinson","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2025,3,29]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,3,29]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaf136","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.08.19.608674","asserted-by":"object"}]},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2025,3,29]]},"article-number":"btaf136"}}