{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:10:05Z","timestamp":1787166605791,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oxford NIHR Biomedical Research Centre","award":["MR\/T031670\/1"],"award-info":[{"award-number":["MR\/T031670\/1"]}]},{"name":"VTCT Foundation","award":["MR\/T031670\/1"],"award-info":[{"award-number":["MR\/T031670\/1"]}]},{"DOI":"10.13039\/501100007155","name":"MRC","doi-asserted-by":"publisher","award":["MR\/T031670\/1"],"award-info":[{"award-number":["MR\/T031670\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The identification of structural variants (SVs) in genomic data represents an ongoing challenge because of difficulties in reliable SV calling leading to reduced sensitivity and specificity. We prepared high-quality DNA from 9 parent\u2013child trios, who had previously undergone short-read whole-genome sequencing (Illumina platform) as part of the Genomics England 100,000 Genomes Project. We reanalysed the genomes using both Bionano optical genome mapping (OGM; 8 probands and one trio) and Nanopore long-read sequencing (Oxford Nanopore Technologies [ONT] platform; all samples). To establish a \u201ctruth\u201d dataset, we asked whether rare proband SV calls (n = 234) made by the Bionano Access (version 1.6.1)\/Solve software (version 3.6.1_11162020) could be verified by individual visualisation using the Integrative Genomics Viewer with either or both of the Illumina and ONT raw sequence. Of these, 222 calls were verified, indicating that Bionano OGM calls have high precision (positive predictive value 95%). We then asked what proportion of the 222 true Bionano SVs had been identified by SV callers in the other two datasets. In the Illumina dataset, sensitivity varied according to variant type, being high for deletions (115\/134; 86%) but poor for insertions (13\/58; 22%). In the ONT dataset, sensitivity was generally poor using the original Sniffles variant caller (48% overall) but improved substantially with use of Sniffles2 (36\/40; 90% and 17\/23; 74% for deletions and insertions, respectively). In summary, we show that the precision of OGM is very high. In addition, when applying the Sniffles2 caller, the sensitivity of SV calling using ONT long-read sequence data outperforms Illumina sequencing for most SV types.<\/jats:p>","DOI":"10.3390\/genes15070925","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T14:59:50Z","timestamp":1721314790000},"page":"925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0115-5851","authenticated-orcid":false,"given":"Yang","family":"Pei","sequence":"first","affiliation":[{"name":"Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4862-0981","authenticated-orcid":false,"given":"Melanie","family":"Tanguy","sequence":"additional","affiliation":[{"name":"Genomics England Limited, One Canada Square, London E14 5AB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Giess","sequence":"additional","affiliation":[{"name":"Genomics England Limited, One Canada Square, London E14 5AB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Dixit","sequence":"additional","affiliation":[{"name":"Clinical Genetics Service, Nottingham University Hospitals NHS Foundation Trust, City Hospital, Nottingham NG5 1PB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1200-2858","authenticated-orcid":false,"given":"Louise C.","family":"Wilson","sequence":"additional","affiliation":[{"name":"North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street Hospital, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Gibbons","sequence":"additional","affiliation":[{"name":"MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R. F.","family":"Twigg","sequence":"additional","affiliation":[{"name":"Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Elgar","sequence":"additional","affiliation":[{"name":"Genomics England Limited, One Canada Square, London E14 5AB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-5481","authenticated-orcid":false,"given":"Andrew O. M.","family":"Wilkie","sequence":"additional","affiliation":[{"name":"Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bagger, F.O., Borgwardt, L., Jespersen, A.S., Hansen, A.R., Bertelsen, B., Kodama, M., and Nielsen, F.C. (2024). Whole genome sequencing in clinical practice. BMC Med. Genom., 17.","DOI":"10.1186\/s12920-024-01795-w"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41525-020-00154-9","article-title":"Best practices for the analytical validation of clinical whole-genome sequencing intended for the diagnosis of germline disease","volume":"5","author":"Marshall","year":"2020","journal-title":"NPJ Genom. 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