TY - JOUR
T1 - Curation and expansion of the Human Phenotype Ontology for systemic autoinflammatory diseases improves phenotype-driven disease-matching
AU - Maassen, Willem
AU - Legger, Geertje
AU - Kul Cinar, Ovgu
AU - van Daele, Paul
AU - Gattorno, Marco
AU - Bader-Meunier, Brigitte
AU - Wouters, Carine
AU - Briggs, Tracy
AU - Johansson, Lennart
AU - van der Velde, Joeri
AU - Swertz, Morris
AU - Omoyinmi, Ebun
AU - Hoppenreijs, Esther
AU - Belot, Alexandre
AU - Eleftheriou, Despina
AU - Caorsi, Roberta
AU - Aeschlimann, Florence
AU - Boursier, Guilaine
AU - Brogan, Paul
AU - Haimel, Matthias
AU - van Gijn, Marielle
N1 - 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.
Funding Information:
This study has been performed as part of the Molecular Testing working group of ERN-RITA and ISSAID (International Society of Systemic Auto-Inflammatory Diseases) members. Additionally, we thank Katy McIntyre, our indoor scientific editor at the Genetics Department in the University Medical Centre Groningen, for her efforts.
Publisher Copyright:
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.
PY - 2023/9/12
Y1 - 2023/9/12
N2 - 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.
AB - 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.
KW - genome diagnostics
KW - Human Phenotype Ontology (HPO)
KW - LIRICAL
KW - systemic autoinflammatory disorders (SAIDs)
KW - variant interpretation
KW - whole exome sequencing (WES)
U2 - 10.3389/fimmu.2023.1215869
DO - 10.3389/fimmu.2023.1215869
M3 - Article
C2 - 37781402
SN - 1664-3224
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1215869
ER -
