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Curation and expansion of the Human Phenotype Ontology for systemic autoinflammatory diseases improves phenotype-driven disease-matching

Maassen, Willem; Legger, Geertje; Kul Cinar, Ovgu; van Daele, Paul; Gattorno, Marco; Bader-Meunier, Brigitte; Wouters, Carine; ... van Gijn, Marielle; + view all (2023) Curation and expansion of the Human Phenotype Ontology for systemic autoinflammatory diseases improves phenotype-driven disease-matching. Frontiers in Immunology , 14 , Article 1215869. 10.3389/fimmu.2023.1215869. Green open access

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Abstract

INTRODUCTION: Accurate and standardized phenotypic descriptions are essential in diagnosing rare diseases and discovering new diseases, and the Human Phenotype Ontology (HPO) system was developed to provide a rich collection of hierarchical phenotypic descriptions. However, although the HPO terms for inborn errors of immunity have been improved and curated, it has not been investigated whether this curation improves the diagnosis of systemic autoinflammatory disease (SAID) patients. Here, we aimed to study if improved HPO annotation for SAIDs enhanced SAID identification and to demonstrate the potential of phenotype-driven genome diagnostics using curated HPO terms for SAIDs. METHODS: We collected HPO terms from 98 genetically confirmed SAID patients across eight different European SAID expertise centers and used the LIRICAL (Likelihood Ratio Interpretation of Clinical Abnormalities) computational algorithm to estimate the effect of HPO curation on the prioritization of the correct SAID for each patient. RESULTS: Our results show that the percentage of correct diagnoses increased from 66% to 86% and that the number of diagnoses with the highest ranking increased from 38 to 45. In a further pilot study, curation also improved HPO-based whole-exome sequencing (WES) analysis, diagnosing 10/12 patients before and 12/12 after curation. In addition, the average number of candidate diseases that needed to be interpreted decreased from 35 to 2. DISCUSSION: This study demonstrates that curation of HPO terms can increase identification of the correct diagnosis, emphasizing the high potential of HPO-based genome diagnostics for SAIDs.

Type: Article
Title: Curation and expansion of the Human Phenotype Ontology for systemic autoinflammatory diseases improves phenotype-driven disease-matching
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2023.1215869
Publisher version: https://doi.org/10.3389/fimmu.2023.1215869
Language: English
Additional information: Copyright © 2023 Maassen, Legger, Kul Cinar, van Daele, Gattorno, Bader-Meunier, Wouters, Briggs, Johansson, van der Velde, Swertz, Omoyinmi, Hoppenreijs, Belot, Eleftheriou, Caorsi, Aeschlimann, Boursier, Brogan, Haimel and van Gijn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: Human Phenotype Ontology (HPO), LIRICAL, genome diagnostics, systemic autoinflammatory disorders (SAIDs), variant interpretation, whole exome sequencing (WES), Humans, Animals, Pilot Projects, Simian Acquired Immunodeficiency Syndrome, Databases, Genetic, Phenotype, Hereditary Autoinflammatory Diseases
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10178264
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