{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T02:24:33Z","timestamp":1787279073289,"version":"build-2736575974"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":67,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","award":["Johnson and Johnson"],"award-info":[{"award-number":["Johnson and Johnson"]}],"id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Human Phenotype Ontology (HPO) provides a standardised framework for disease-phenotype associations. Given the complexity of systemic autoimmune rheumatic diseases (SARDs) and the absence of prior evaluations, we aimed to assess the completeness of HPO terms capturing SARD-related phenotypic features and SARD-phenotype associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole-exome sequencing was performed in 111 individuals from the LEAP (Lupus Extended Autoimmune Phenotype) cohort, a cohort of adult and paediatric SARD patients, who had at least one feature suggestive of a monogenic disease. We evaluated the completeness of HPO annotations relative to documented phenotypic data and SARD diagnoses. We also explored the potential added value of these terms descriptively and by using a phenotype-based genomic tool, Emedgene.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At least one missing HPO term occurred in 36.9% of our patients. Five patient features could not be mapped to existing HPO terms: anti-chromatin antibody, autoimmune hepatitis, scleroderma renal crisis, shrinking lung syndrome, and tenosynovitis. The HPO term \u201cscleroderma\u201d was misdefined, and six HPO terms did not include six linked SARDs in the respective disease-association section. In a random sample of 10 SARD patients, we also demonstrated that HPO terms affect the gene variant prioritisation on the Emedgene platform.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is the first study to examine the HPO term coverage in SARDs and assess the potential impact of missing terms. We have proposed to the HPO hub the inclusion of absent or misdefined terms and the addition of missing SARD-HPO term associations. We anticipate that expanding the HPO will enhance our ability to characterise the genetic basis of SARDs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04432-0","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:34:12Z","timestamp":1781498052000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Refining Human Phenotype Ontology (HPO) to enable better phenotype-genotype integration in systemic autoimmune rheumatic diseases"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7382-9958","authenticated-orcid":false,"given":"Anastasia-Vasiliki","family":"Madenidou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian I.","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Dyball","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane L.","family":"Herrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Chinoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian N.","family":"Bruce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Briggs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"4432_CR1","unstructured":"Human Phenotype Ontology. 2026 https:\/\/hpo.jax.org\/about. 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AVM is funded by the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (BRC) (NIHR203308). AVM has received grant support from UCB and Janssen and speaker honoraria from Boehringer Ingelheim. INB has received grant support from Genzyme\/Sanofi, GlaxoSmithKline, Roche, Jansen and UCB; consulting fees from AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck Serono and UCB and was a speaker for AstraZeneca, GlaxoSmithKline and UCB. BP is supported by the NIHR Manchester Biomedical Research Centre (NIHR203308) and NIHR Manchester Clinical Research Facility. The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care. BP has received grant support from Genzyme\/Sanofi and GSK, honoraria from Fresenius-Kabi and AbbVie and was a speaker for Eli Lilly and Roche. AS has received speaker honoraria from Merck KGaA and a research grant from NovoNordisk. HC has received grant support from Pfizer; advisory board member for Astra Zeneca, Pfizer, Argenx, Johnson & Johnson; Data and Science Monitoring Board chair for Horizon Therapeutics; speaker fees from UCB. SD has received grant support from Novartis. TAB and GIR have received grant support from Janssen.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"293"}}