Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources

Sebastian Köhler^{1

2

3}, Leigh Carmody^{3

4}, Nicole Vasilevsky^{3

5}, Julius O B Jacobsen^{3

6}, Daniel Danis^{3

4}, Jean-Philippe Gourdine^{3

5}, Michael Gargano^{3

4}, Nomi L Harris^{3

7}, Nicolas Matentzoglu^{3

8}, Julie A McMurry^{3

9}, David Osumi-Sutherland^{3

8}, Valentina Cipriani^{3

10

11

12}, James P Balhoff^{3

13}, Tom Conlin^{3

9}, Hannah Blau^{3

4}, Gareth Baynam^{14

15

16

17

18}, Richard Palmer¹⁷, Dylan Gratian¹⁴, Hugh Dawkins¹⁸, Michael Segal¹⁹, Anna C Jansen^{20

21}, Ahmed Muaz^{3

22}, Willie H Chang²³, Jenna Bergerson²⁴, Stanley J F Laulederkind²⁵, Zafer Yüksel²⁶, Sergi Beltran^{27

28}, Alexandra F Freeman²⁴, Panagiotis I Sergouniotis²⁹, Daniel Durkin⁴, Andrea L Storm^{30

31}, Marc Hanauer³², Michael Brudno²³, Susan M Bello³³, Murat Sincan³⁴, Kayli Rageth³⁴, Matthew T Wheeler³⁵, Renske Oegema³⁶, Halima Lourghi³², Maria G Della Rocca^{30

31}, Rachel Thompson³⁷, Francisco Castellanos⁴, James Priest³⁸, Charlotte Cunningham-Rundles³⁹, Ayushi Hegde⁴, Ruth C Lovering⁴⁰, Catherine Hajek³⁴, Annie Olry³², Luigi Notarangelo²⁴, Morgan Similuk²⁴, Xingmin A Zhang^{3

4}, David Gómez-Andrés⁴¹, Hanns Lochmüller^{27

42

43

44}, Hélène Dollfus⁴⁵, Sergio Rosenzweig⁴⁶, Shruti Marwaha³⁵, Ana Rath³², Kathleen Sullivan⁴⁷, Cynthia Smith³³, Joshua D Milner²⁴, Dorothée Leroux⁴⁵, Cornelius F Boerkoel³⁴, Amy Klion²⁴, Melody C Carter²⁴, Tudor Groza^{3

22}, Damian Smedley^{3

6}, Melissa A Haendel^{3

5

9}, Chris Mungall^{3

7}, Peter N Robinson^{3

4

48}

Affiliations

¹ Charité Centrum für Therapieforschung, Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany.
² Einstein Center Digital Future, Berlin 10117, Germany.
³ Monarch Initiative, monarchinitiative.org.
⁴ The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
⁵ Oregon Health & Science University, Portland, OR 97217, USA.
⁶ Genomics England, Queen Mary University of London, Dawson Hall, Charterhouse Square, London EC1M 6BQ, UK.
⁷ Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
⁸ European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.
⁹ Linus Pauling institute, Oregon State University, Corvallis, OR, USA.
¹⁰ William Harvey Research Institute, Queen Mary University College of London.
¹¹ UCL Genetics Institute, University College of London.
¹² UCL Institute of Ophthalmology, University College of London.
¹³ Renaissance Computing Institute, University of North Carolina at Chapel Hill.
¹⁴ Western Australian Register of Developmental Anomalies and Genetic Services of Western Australia, Department of Health, Government of Western Australia, WA, Australia.
¹⁵ School of Paediatrics and Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
¹⁶ Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.
¹⁷ Spatial Sciences, Department of Science and Engineering, Curtin University, Perth, WA, Australia.
¹⁸ The Office of Population Health Genomics, Department of Health, Government of Western Australia, Perth, WA, Australia.
¹⁹ SimulConsult, Chestnut Hill, MA, USA.
²⁰ Neurogenetics Research Group, Vrije Universiteit Brussel, Brussels, Belgium.
²¹ Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel, Brussels, Belgium.
²² Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
²³ Centre for Computational Medicine, Hospital for Sick Children and Department of Computer Science, University of Toronto, Toronto, Canada.
²⁴ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
²⁵ Rat Genome Database, Department of Biomedical Engineering, Medical College of Wisconsin & Marquette University, 8701 Watertown Plank Road Milwaukee, WI 53226, USA.
²⁶ Bioscientia GmbH, Ingelheim, Germany.
²⁷ CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Baldiri Reixac 4, Barcelona 08028, Spain.
²⁸ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
²⁹ University of Manchester & Manchester Royal Eye Hospital, Manchester, UK.
³⁰ ICF, Rockville, MD, USA.
³¹ National Center for Advancing Translational Sciences, Office of Rare Diseases Research, National Institutes of Health, Bethesda, MD, USA.
³² INSERM, US14-Orphanet, Plateforme Maladies Rares, 75014 Paris, France.
³³ The Jackson Laboratory, Bar Harbor, ME, USA.
³⁴ Sanford Imagenetics, Sanford Health, Sioux Falls, SD, USA.
³⁵ Center for Undiagnosed Diseases, Stanford University School of Medicine, Stanford, CA, USA.
³⁶ Department of Genetics, University Medical Center Utrecht, the Netherlands.
³⁷ Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
³⁸ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
³⁹ Mount Sinai School of Medicine, New York, NY, USA.
⁴⁰ Institute of Cardiovascular Science, University College London, UK.
⁴¹ Child Neurology Unit. Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
⁴² Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany.
⁴³ Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.
⁴⁴ Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada.
⁴⁵ Centre for Rare Eye Diseases CARGO, SENSGENE FSMR Network, Strasbourg University Hospital, Strasbourg, France.
⁴⁶ Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, USA.
⁴⁷ Department of Pediatrics, Division of Allergy Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
⁴⁸ Institute for Systems Genomics, University of Connecticut, Farmington, CT, USA.

PMID: 30476213
PMCID: PMC6324074
DOI: 10.1093/nar/gky1105

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources

Sebastian Köhler et al. Nucleic Acids Res. 2019.

. 2019 Jan 8;47(D1):D1018-D1027.

doi: 10.1093/nar/gky1105.

Authors

Affiliations

¹ Charité Centrum für Therapieforschung, Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany.
² Einstein Center Digital Future, Berlin 10117, Germany.
³ Monarch Initiative, monarchinitiative.org.
⁴ The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
⁵ Oregon Health & Science University, Portland, OR 97217, USA.
⁶ Genomics England, Queen Mary University of London, Dawson Hall, Charterhouse Square, London EC1M 6BQ, UK.
⁷ Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
⁸ European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.
⁹ Linus Pauling institute, Oregon State University, Corvallis, OR, USA.
¹⁰ William Harvey Research Institute, Queen Mary University College of London.
¹¹ UCL Genetics Institute, University College of London.
¹² UCL Institute of Ophthalmology, University College of London.
¹³ Renaissance Computing Institute, University of North Carolina at Chapel Hill.
¹⁴ Western Australian Register of Developmental Anomalies and Genetic Services of Western Australia, Department of Health, Government of Western Australia, WA, Australia.
¹⁵ School of Paediatrics and Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
¹⁶ Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.
¹⁷ Spatial Sciences, Department of Science and Engineering, Curtin University, Perth, WA, Australia.
¹⁸ The Office of Population Health Genomics, Department of Health, Government of Western Australia, Perth, WA, Australia.
¹⁹ SimulConsult, Chestnut Hill, MA, USA.
²⁰ Neurogenetics Research Group, Vrije Universiteit Brussel, Brussels, Belgium.
²¹ Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel, Brussels, Belgium.
²² Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
²³ Centre for Computational Medicine, Hospital for Sick Children and Department of Computer Science, University of Toronto, Toronto, Canada.
²⁴ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
²⁵ Rat Genome Database, Department of Biomedical Engineering, Medical College of Wisconsin & Marquette University, 8701 Watertown Plank Road Milwaukee, WI 53226, USA.
²⁶ Bioscientia GmbH, Ingelheim, Germany.
²⁷ CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Baldiri Reixac 4, Barcelona 08028, Spain.
²⁸ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
²⁹ University of Manchester & Manchester Royal Eye Hospital, Manchester, UK.
³⁰ ICF, Rockville, MD, USA.
³¹ National Center for Advancing Translational Sciences, Office of Rare Diseases Research, National Institutes of Health, Bethesda, MD, USA.
³² INSERM, US14-Orphanet, Plateforme Maladies Rares, 75014 Paris, France.
³³ The Jackson Laboratory, Bar Harbor, ME, USA.
³⁴ Sanford Imagenetics, Sanford Health, Sioux Falls, SD, USA.
³⁵ Center for Undiagnosed Diseases, Stanford University School of Medicine, Stanford, CA, USA.
³⁶ Department of Genetics, University Medical Center Utrecht, the Netherlands.
³⁷ Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
³⁸ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
³⁹ Mount Sinai School of Medicine, New York, NY, USA.
⁴⁰ Institute of Cardiovascular Science, University College London, UK.
⁴¹ Child Neurology Unit. Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
⁴² Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany.
⁴³ Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.
⁴⁴ Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada.
⁴⁵ Centre for Rare Eye Diseases CARGO, SENSGENE FSMR Network, Strasbourg University Hospital, Strasbourg, France.
⁴⁶ Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, USA.
⁴⁷ Department of Pediatrics, Division of Allergy Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
⁴⁸ Institute for Systems Genomics, University of Connecticut, Farmington, CT, USA.

PMID: 30476213
PMCID: PMC6324074
DOI: 10.1093/nar/gky1105

Abstract

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO's interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes.

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Figures

**Figure 1.**
Overview of the **clinical modifier** (A, left) **and clinical course** (B, right) subontologies. These subontology terms can be used in combination with existing HPO terms to qualify and enrich their meaning. (C) A schematic presentation of one HPO annotation for the disease familial cold autoinflammatory syndrome 2 (FCAS2). In a publication on this disease, three of three reported patients were found to have episodic fever with infantile (or earlier) onset that was triggered by exposure to cold (63).

**Figure 2.**
Screenshot of the new HPO Website application. Users can search for HPO terms, annotated diseases, or disease-associated genes using an autocomplete widget. The hierarchical structure of the ontology is shown in an abbreviated fashion for clarity’s sake. Only the direct parent and child terms of the currently displayed term are shown in the hierarchy. The total number of decedent terms is shown for each term in the hierarchy to help users decide which parts of the ontology to explore.

See this image and copyright information in PMC

References

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Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources

Affiliations

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical