{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:27:16Z","timestamp":1783427236448,"version":"3.54.6"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["P20GM103449"],"award-info":[{"award-number":["P20GM103449"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["UM1HL098123"],"award-info":[{"award-number":["UM1HL098123"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["U01HL153009"],"award-info":[{"award-number":["U01HL153009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Structural variants (SVs) play a causal role in numerous diseases but can be difficult to detect and accurately genotype (determine zygosity) with short-read genome sequencing data (SRS). Improving SV genotyping accuracy in SRS data, particularly for the many SVs first detected with long-read sequencing, will improve our understanding of genetic variation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>NPSV-deep is a deep learning-based approach for genotyping previously reported insertion and deletion SVs that recasts this task as an image similarity problem. NPSV-deep predicts the SV genotype based on the similarity between pileup images generated from the actual SRS data and matching SRS simulations. We show that NPSV-deep consistently matches or improves upon the state-of-the-art for SV genotyping accuracy across different SV call sets, samples and variant types, including a 25% reduction in genotyping errors for the Genome-in-a-Bottle (GIAB) high-confidence SVs. NPSV-deep is not limited to the SVs as described; it improves deletion genotyping concordance a further 1.5 percentage points for GIAB SVs (92%) by automatically correcting imprecise\/incorrectly described SVs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Python\/C++ source code and pre-trained models freely available at https:\/\/github.com\/mlinderm\/npsv2.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae129","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T05:12:47Z","timestamp":1709701967000},"source":"Crossref","is-referenced-by-count":7,"title":["NPSV-deep: a deep learning method for genotyping structural variants in short read genome sequencing data"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9643-7148","authenticated-orcid":false,"given":"Michael D","family":"Linderman","sequence":"first","affiliation":[{"name":"Department of Computer Science, Middlebury College , Middlebury, VT 05753, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7136-5688","authenticated-orcid":false,"given":"Jacob","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Middlebury College , Middlebury, VT 05753, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alderik","family":"van der Heyde","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Middlebury College , Middlebury, VT 05753, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6807-7632","authenticated-orcid":false,"given":"Eliza","family":"Wieman","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Middlebury College , Middlebury, VT 05753, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Brey","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Middlebury College , Middlebury, VT 05753, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Middlebury College , Middlebury, VT 05753, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Middlebury College , Middlebury, VT 05753, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9834-2978","authenticated-orcid":false,"given":"Zahra","family":"Shamsi","sequence":"additional","affiliation":[{"name":"Google, Mountain View , CA 94043, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-4502","authenticated-orcid":false,"given":"Jeremiah","family":"Liu","sequence":"additional","affiliation":[{"name":"Google, Mountain View , CA 94043, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8527-5027","authenticated-orcid":false,"given":"Bruce D","family":"Gelb","sequence":"additional","affiliation":[{"name":"Mindich Child Health and Development Institute and the Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai , New York, NY 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5240-9604","authenticated-orcid":false,"given":"Ali","family":"Bashir","sequence":"additional","affiliation":[{"name":"Google, Mountain View , CA 94043, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"2024032107584396600_btae129-B1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nrg2958","article-title":"Genome structural variation discovery and genotyping","volume":"12","author":"Alkan","year":"2011","journal-title":"Nat Rev Genet"},{"key":"2024032107584396600_btae129-B2","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1093\/bioinformatics\/btx813","article-title":"SV2: accurate structural variation genotyping and de novo mutation detection from whole genomes","volume":"34","author":"Antaki","year":"2018","journal-title":"Bioinformatics"},{"key":"2024032107584396600_btae129-B3","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2018.12.019","article-title":"Characterizing the major structural variant alleles of the human genome","volume":"176","author":"Audano","year":"2019","journal-title":"Cell"},{"key":"2024032107584396600_btae129-B4","doi-asserted-by":"crossref","first-page":"107417","DOI":"10.1016\/j.compbiolchem.2020.107417","article-title":"CNNGENO: a high-precision deep learning based strategy for the calling of structural variation genotype","volume":"94","author":"Bai","year":"2021","journal-title":"Comput Biol Chem"},{"key":"2024032107584396600_btae129-B5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s13059-021-02380-5","article-title":"Samplot: a platform for structural variant visual validation and automated filtering","volume":"22","author":"Belyeu","year":"2021","journal-title":"Genome Biol"},{"key":"2024032107584396600_btae129-B6","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1016\/j.cell.2022.08.004","article-title":"High-coverage whole-genome sequencing of the expanded 1000 genomes project cohort including 602 trios","volume":"185","author":"Byrska-Bishop","year":"2022","journal-title":"Cell"},{"key":"2024032107584396600_btae129-B7","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1186\/s12859-019-3299-y","article-title":"DeepSV: accurate calling of genomic deletions from high-throughput sequencing data using deep convolutional neural network","volume":"20","author":"Cai","year":"2019","journal-title":"BMC Bioinformatics"},{"key":"2024032107584396600_btae129-B8","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1038\/s41467-019-11146-4","article-title":"Comprehensive evaluation and characterisation of short read general-purpose structural variant calling software","volume":"10","author":"Cameron","year":"2019","journal-title":"Nat Commun"},{"key":"2024032107584396600_btae129-B9","doi-asserted-by":"crossref","first-page":"giz110","DOI":"10.1093\/gigascience\/giz110","article-title":"Evaluation of computational genotyping of structural variation for clinical diagnoses","volume":"8","author":"Chander","year":"2019","journal-title":"Gigascience"},{"key":"2024032107584396600_btae129-B10","author":"Chapman","year":"2021"},{"key":"2024032107584396600_btae129-B11","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s13059-019-1909-7","article-title":"Paragraph: a graph-based structural variant genotyper for short-read sequence data","volume":"20","author":"Chen","year":"2019","journal-title":"Genome Biol"},{"key":"2024032107584396600_btae129-B12","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1093\/bioinformatics\/btv710","article-title":"Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications","volume":"32","author":"Chen","year":"2016","journal-title":"Bioinformatics"},{"key":"2024032107584396600_btae129-B13","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/nmeth.3505","article-title":"SpeedSeq: ultra-fast personal genome analysis and interpretation","volume":"12","author":"Chiang","year":"2015","journal-title":"Nat Methods"},{"key":"2024032107584396600_btae129-B14","doi-asserted-by":"crossref","first-page":"e113324","DOI":"10.1371\/journal.pone.0113324","article-title":"GINDEL: accurate genotype calling of insertions and deletions from low coverage population sequence reads","volume":"9","author":"Chu","year":"2014","journal-title":"PLoS One"},{"key":"2024032107584396600_btae129-B15","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1101\/gr.210500.116","article-title":"A reference data set of 5.4 million phased human variants validated by genetic inheritance from sequencing a three-generation 17-member pedigree","volume":"27","author":"Eberle","year":"2017","journal-title":"Genome Res"},{"key":"2024032107584396600_btae129-B16","doi-asserted-by":"crossref","first-page":"eabf7117","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":"2024032107584396600_btae129-B17","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/s41588-022-01043-w","article-title":"Pangenome-based genome inference allows efficient and accurate genotyping across a wide spectrum of variant classes","volume":"54","author":"Ebler","year":"2022","journal-title":"Nat Genet"},{"key":"2024032107584396600_btae129-B18","doi-asserted-by":"crossref","first-page":"5402","DOI":"10.1038\/s41467-019-13341-9","article-title":"GraphTyper2 enables population-scale genotyping of structural variation using pangenome graphs","volume":"10","author":"Eggertsson","year":"2019","journal-title":"Nat Commun"},{"key":"2024032107584396600_btae129-B19","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":"2024032107584396600_btae129-B20","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nrg.2016.49","article-title":"Coming of age: ten years of next-generation sequencing technologies","volume":"17","author":"Goodwin","year":"2016","journal-title":"Nat Rev Genet"},{"key":"2024032107584396600_btae129-B21","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ymeth.2016.01.020","article-title":"Structural variation detection using next-generation sequencing data","volume":"102","author":"Guan","year":"2016","journal-title":"Methods"},{"key":"2024032107584396600_btae129-B22","first-page":"1735","author":"Hadsell","year":"2006"},{"key":"2024032107584396600_btae129-B23","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/ng.3200","article-title":"Large multiallelic copy number variations in humans","volume":"47","author":"Handsaker","year":"2015","journal-title":"Nat Genet"},{"key":"2024032107584396600_btae129-B24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13059-020-1941-7","article-title":"Genotyping structural variants in pangenome graphs using the vg toolkit","volume":"21","author":"Hickey","year":"2020","journal-title":"Genome Biol"},{"key":"2024032107584396600_btae129-B25","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/bioinformatics\/btr708","article-title":"ART: a next-generation sequencing read simulator","volume":"28","author":"Huang","year":"2012","journal-title":"Bioinformatics"},{"key":"2024032107584396600_btae129-B26","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/s41592-022-01753-3","article-title":"Jasmine and iris: population-scale structural variant comparison and analysis","volume":"20","author":"Kirsche","year":"2023","journal-title":"Nat Methods"},{"key":"2024032107584396600_btae129-B27","author":"Koch","year":"2015"},{"key":"2024032107584396600_btae129-B28","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13059-019-1720-5","article-title":"Comprehensive evaluation of structural variation detection algorithms for whole genome sequencing","volume":"20","author":"Kosugi","year":"2019","journal-title":"Genome Biol"},{"key":"2024032107584396600_btae129-B29","doi-asserted-by":"crossref","first-page":"R84","DOI":"10.1186\/gb-2014-15-6-r84","article-title":"LUMPY: a probabilistic framework for structural variant discovery","volume":"15","author":"Layer","year":"2014","journal-title":"Genome Biol"},{"key":"2024032107584396600_btae129-B30","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41586-023-05896-x","article-title":"A draft human pangenome reference","volume":"617","author":"Liao","year":"2023","journal-title":"Nature"},{"key":"2024032107584396600_btae129-B31","doi-asserted-by":"crossref","first-page":"giab046","DOI":"10.1093\/gigascience\/giab046","article-title":"NPSV: a simulation-driven approach to genotyping structural variants in whole-genome sequencing data","volume":"10","author":"Linderman","year":"2021","journal-title":"Gigascience"},{"key":"2024032107584396600_btae129-B32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s13059-019-1828-7","article-title":"Structural variant calling: the long and the short of it","volume":"20","author":"Mahmoud","year":"2019","journal-title":"Genome Biol"},{"key":"2024032107584396600_btae129-B33","author":"Marcus","year":"2018"},{"key":"2024032107584396600_btae129-B34","author":"Martin","year":"2016"},{"key":"2024032107584396600_btae129-B35","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41592-023-01799-x","article-title":"Cue: a deep-learning framework for structural variant discovery and genotyping","volume":"20","author":"Popic","year":"2023","journal-title":"Nat Methods"},{"key":"2024032107584396600_btae129-B36","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nbt.4235","article-title":"A universal SNP and small-indel variant caller using deep neural networks","volume":"36","author":"Poplin","year":"2018","journal-title":"Nat Biotechnol"},{"key":"2024032107584396600_btae129-B37","doi-asserted-by":"crossref","first-page":"i333","DOI":"10.1093\/bioinformatics\/bts378","article-title":"DELLY: structural variant discovery by integrated paired-end and split-read analysis","volume":"28","author":"Rausch","year":"2012","journal-title":"Bioinformatics"},{"key":"2024032107584396600_btae129-B38","doi-asserted-by":"crossref","first-page":"3994","DOI":"10.1093\/bioinformatics\/btv478","article-title":"svviz: a read viewer for validating structural variants","volume":"31","author":"Spies","year":"2015","journal-title":"Bioinformatics"},{"key":"2024032107584396600_btae129-B39","first-page":"1","article-title":"Generalizing from a few examples","volume":"53","author":"Wang","year":"2021","journal-title":"ACM Comput Surv"},{"key":"2024032107584396600_btae129-B40","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nrg3373","article-title":"Phenotypic impact of genomic structural variation: insights from and for human disease","volume":"14","author":"Weischenfeldt","year":"2013","journal-title":"Nat Rev Genet"},{"key":"2024032107584396600_btae129-B41","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\/btae129\/56873975\/btae129.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/3\/btae129\/57038886\/btae129.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/3\/btae129\/57038886\/btae129.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T08:54:17Z","timestamp":1711011257000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btae129\/7623007"}},"subtitle":[],"editor":[{"given":"Inanc","family":"Birol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,1]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btae129","relation":{},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,3,1]]},"published":{"date-parts":[[2024,3,1]]},"article-number":"btae129"}}