{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T11:17:30Z","timestamp":1772795850085,"version":"3.50.1"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K12148"],"award-info":[{"award-number":["21K12148"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K11886"],"award-info":[{"award-number":["23K11886"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K11055"],"award-info":[{"award-number":["24K11055"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Inform Decis Mak"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Virtual Gene Panels (VGP) comprising disease-associated causal genes are utilized in the diagnosis of rare genetic diseases to evaluate candidate genes identified by whole-genome and whole-exome sequencing. VGPs generated by the PanelApp software were utilized in a UK 100,000 Genome Project pilot study to filter candidate genes, thus enhancing diagnostic efficiency for rare diseases. However, PanelApp also filtered out disease-causing genes in nearly 50% of the cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we propose various methods for optimized approach to design VGPs that significantly improve the diagnostic efficiency by leveraging the hierarchical structure of the Mondo disease ontology, without excluding disease-causing genes. We also performed computational experiments on an evaluation dataset comprising 74 patients to determine the optimal VGP design method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results demonstrate that the proposed method can significantly enhance rare disease diagnosis efficiency by automatically identifying candidate genes. The proposed method successfully designed VGPs that improve diagnosis efficiency without excluding disease-causing genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We have developed novel methods for VGP design that leverage the hierarchical structure of the Mondo disease ontology to improve rare genetic disease diagnosis efficiency. This approach identifies candidate genes without excluding disease-causing genes, and thereby improves diagnostic efficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12911-025-02910-2","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T07:19:28Z","timestamp":1738739968000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ontology-based expansion of virtual gene panels to improve diagnostic efficiency for rare genetic diseases"],"prefix":"10.1186","volume":"25","author":[{"given":"Jaemoon","family":"Shin","sequence":"first","affiliation":[]},{"given":"Toyofumi","family":"Fujiwara","sequence":"additional","affiliation":[]},{"given":"Hirotomo","family":"Saitsu","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7538-5337","authenticated-orcid":false,"given":"Atsuko","family":"Yamaguchi","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"issue":"2","key":"2910_CR1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/d41573-019-00180-y","volume":"19","author":"M Haendel","year":"2020","unstructured":"Haendel M, Vasilevsky N, Unni D, Bologa C, Harris N, Rehm H, et al. How many rare diseases are there? Nat Rev Drug Discov. 2020;19(2):77\u20138. https:\/\/doi.org\/10.1038\/d41573-019-00180-y.","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"2910_CR2","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13073-022-01026-w","volume":"14","author":"S Marwaha","year":"2022","unstructured":"Marwaha S, Knowles JW, Ashley EA. A guide for the diagnosis of rare and undiagnosed disease: beyond the exome. Genome Med. 2022;14(1):23. https:\/\/doi.org\/10.1186\/s13073-022-01026-w.","journal-title":"Genome Med"},{"issue":"12","key":"2910_CR3","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1136\/jmedgenet-2019-106111","volume":"56","author":"D Bick","year":"2019","unstructured":"Bick D, Jones M, Taylor SL, Taft RJ, Belmont J. Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases. J Med Genet. 2019;56(12):783\u201391. https:\/\/doi.org\/10.1136\/jmedgenet-2019-106111.","journal-title":"J Med Genet"},{"issue":"10197","key":"2910_CR4","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S0140-6736(19)31274-7","volume":"394","author":"AL Wise","year":"2019","unstructured":"Wise AL, Manolio TA, Mensah GA, Peterson JF, Roden DM, Tamburro C, et al. Genomic medicine for undiagnosed diseases. Lancet. 2019;394(10197):533\u201340. https:\/\/doi.org\/10.1016\/S0140-6736(19)31274-7.","journal-title":"Lancet"},{"issue":"11","key":"2910_CR5","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1038\/s41588-019-0528-2","volume":"51","author":"AR Martin","year":"2019","unstructured":"Martin AR, Williams E, Foulger RE, Leigh S, Daugherty LC, Niblock O, et al. PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nat Genet. 2019;51(11):1560\u20135. https:\/\/doi.org\/10.1038\/s41588-019-0528-2.","journal-title":"Nat Genet"},{"key":"2910_CR6","unstructured":"Genomics England Quality Management System -GUI-BIO-004 PanelApp Handbook GUI-BIO-004 PanelApp Handbook. Available from: https:\/\/panelapp.genomicsengland.co.uk\/media\/files\/PanelApp_Handbook_V35_10Nov2022.pdf. Cited 2023 Aug 2."},{"key":"2910_CR7","doi-asserted-by":"publisher","unstructured":"Smedley D, Smith KR, Martin A, Thomas EA, McDonagh EM, Cipriani V, et al.\u00a0100,000 genomes pilot on rare-disease diagnosis in health care\u2014preliminary report. N Engl J Med. 2021;385(20):1868\u201380. https:\/\/doi.org\/10.1056\/NEJMoa2035790.","DOI":"10.1056\/NEJMoa2035790"},{"issue":"D1","key":"2910_CR8","doi-asserted-by":"publisher","first-page":"D704","DOI":"10.1093\/nar\/gkz997","volume":"48","author":"KA Shefchek","year":"2020","unstructured":"Shefchek KA, Harris NL, Gargano M, Matentzoglu N, Unni D, Brush M, et al. The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species. Nucleic Acids Res. 2020;48(D1):D704\u201315. https:\/\/doi.org\/10.1093\/nar\/gkz997.","journal-title":"Nucleic Acids Res"},{"key":"2910_CR9","doi-asserted-by":"publisher","unstructured":"Kawashima S. An Introduction to the NBDC RDF portal: accelerating the utilization of semantically integrated life science data.\u00a0Database (Oxford). 2016;59(4):232\u201340. https:\/\/doi.org\/10.1241\/johokanri.59.232.","DOI":"10.1241\/johokanri.59.232"},{"key":"2910_CR10","unstructured":"Kamada M, Katayama T, Kawashima S, Kojima R, Nakatsui M, Okuno Y. Med2RDF: semantic biomedical knowledge-base and APIs for the clinical genome medicine. In: Cornet R, Waagmeester A, editors. Proceedings of the 12th International Conference on Semantic Web Applications and Tools for Health Care and Life Sciences (SWAT4HCLS 2019); 2019; Edinburgh, Scotland. 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Hum Mutat. 2022;43(6):734\u201342. https:\/\/doi.org\/10.1002\/humu.24341.","journal-title":"Hum Mutat"}],"container-title":["BMC Medical Informatics and Decision Making"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12911-025-02910-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12911-025-02910-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12911-025-02910-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T09:25:49Z","timestamp":1772789149000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12911-025-02910-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":15,"journal-issue":{"issue":"S1","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["2910"],"URL":"https:\/\/doi.org\/10.1186\/s12911-025-02910-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.10.31.24315563","asserted-by":"object"}]},"ISSN":["1472-6947"],"issn-type":[{"value":"1472-6947","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]},"assertion":[{"value":"15 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"59"}}