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

Willem Maassen; Geertje Legger; Ovgu Kul Cinar; Paul van Daele; Marco Gattorno; Brigitte Bader-Meunier; Carine Wouters; Tracy Briggs; Lennart Johansson; Joeri van der Velde; Morris Swertz; Ebun Omoyinmi; Esther Hoppenreijs; Alexandre Belot; Despina Eleftheriou; Roberta Caorsi; Florence Aeschlimann; Guilaine Boursier; Paul Brogan; Matthias Haimel; Marielle van Gijn

doi:10.3389/fimmu.2023.1215869

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

Willem Maassen, Geertje Legger, Ovgu Kul Cinar, Paul van Daele, Marco Gattorno, Brigitte Bader-Meunier, Carine Wouters, Tracy Briggs, Lennart Johansson, Joeri van der Velde, Morris Swertz, Ebun Omoyinmi, Esther Hoppenreijs, Alexandre Belot, Despina Eleftheriou, Roberta Caorsi, Florence Aeschlimann, Guilaine Boursier, Paul Brogan, Matthias HaimelMarielle van Gijn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

2 Citations (Scopus)

5 Downloads (Pure)

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.

Original language	English
Article number	1215869
Journal	Frontiers in Immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1215869
Publication status	Published - 12 Sept 2023

Bibliographical note

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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3389/fimmu.2023.1215869Licence: CC BY

Curation and expansion of the Human Phenotype Ontology for systemic autoinflammatory diseases improves phenotype-driven disease-matchingFinal published version, 710 KBLicence: CC BY

Cite this

Maassen, W., Legger, G., Kul Cinar, O., van Daele, P., Gattorno, M., Bader-Meunier, B., Wouters, C., Briggs, T., Johansson, L., van der Velde, J., Swertz, M., Omoyinmi, E., Hoppenreijs, E., Belot, A., Eleftheriou, D., Caorsi, R., Aeschlimann, F., Boursier, G., Brogan, P., ... van Gijn, M. (2023). Curation and expansion of the Human Phenotype Ontology for systemic autoinflammatory diseases improves phenotype-driven disease-matching. Frontiers in Immunology, 14, Article 1215869. https://doi.org/10.3389/fimmu.2023.1215869

@article{f70754c5a16642a0bc87821ba65e6624,

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

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.",

author = "Willem Maassen and Geertje Legger and {Kul Cinar}, Ovgu and {van Daele}, Paul and Marco Gattorno and Brigitte Bader-Meunier and Carine Wouters and Tracy Briggs and Lennart Johansson and {van der Velde}, Joeri and Morris Swertz and Ebun Omoyinmi and Esther Hoppenreijs and Alexandre Belot and Despina Eleftheriou and Roberta Caorsi and Florence Aeschlimann and Guilaine Boursier and Paul Brogan and Matthias Haimel and {van Gijn}, Marielle",

note = "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 {\textcopyright} 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.",

year = "2023",

month = sep,

day = "12",

doi = "10.3389/fimmu.2023.1215869",

language = "English",

volume = "14",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media SA",

}

Maassen, W, Legger, G, Kul Cinar, O, van Daele, P, Gattorno, M, Bader-Meunier, B, Wouters, C, Briggs, T, Johansson, L, van der Velde, J, Swertz, M, Omoyinmi, E, Hoppenreijs, E, Belot, A, Eleftheriou, D, Caorsi, R, Aeschlimann, F, Boursier, G, Brogan, P, Haimel, M & van Gijn, M 2023, 'Curation and expansion of the Human Phenotype Ontology for systemic autoinflammatory diseases improves phenotype-driven disease-matching', Frontiers in Immunology, vol. 14, 1215869. https://doi.org/10.3389/fimmu.2023.1215869

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 - 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.

UR - http://www.scopus.com/inward/record.url?scp=85172387226&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2023.1215869

DO - 10.3389/fimmu.2023.1215869

M3 - Article

C2 - 37781402

AN - SCOPUS:85172387226

SN - 1664-3224

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1215869

ER -

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

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this