The Human Phenotype Ontology in 2021

Author:

Köhler Sebastian12,Gargano Michael23,Matentzoglu Nicolas245,Carmody Leigh C23,Lewis-Smith David67,Vasilevsky Nicole A28,Danis Daniel,Balagura Ganna910,Baynam Gareth1112,Brower Amy M13,Callahan Tiffany J14,Chute Christopher G15,Est Johanna L16,Galer Peter D1718,Ganesan Shiva1718,Griese Matthias1619,Haimel Matthias2021,Pazmandi Julia202122,Hanauer Marc23,Harris Nomi L224,Hartnett Michael J13,Hastreiter Maximilian16,Hauck Fabian1625,He Yongqun26,Jeske Tim16,Kearney Hugh27,Kindle Gerhard2829,Klein Christoph16,Knoflach Katrin1619,Krause Roland30,Lagorce David23,McMurry Julie A231,Miller Jillian A13,Munoz-Torres Monica C231,Peters Rebecca L13,Rapp Christina K1619,Rath Ana M23,Rind Shahmir A3233,Rosenberg Avi Z34ORCID,Segal Michael M35,Seidel Markus G36,Smedley Damian37,Talmy Tomer3839,Thomas Yarlalu40,Wiafe Samuel A41,Xian Julie1742,Yüksel Zafer43,Helbig Ingo4445,Mungall Christopher J224,Haendel Melissa A2831,Robinson Peter N2322ORCID

Affiliation:

1. Ada Health GmbH, Berlin, Germany

2. Monarch Initiative

3. The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA

4. Semanticly Ltd, London, UK

5. European Bioinformatics Institute (EMBL-EBI)

6. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

7. Clinical Neurosciences, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

8. Oregon Clinical & Translational Research Institute, Oregon Health & Science University

9. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genoa, Italy

10. Pediatric Neurology and Muscular Diseases Unit, IRCCS ‘G. Gaslini’ Institute, Genoa, Italy

11. Western Australian Register of Developmental Anomalies, King Edward memorial Hospital, Perth, Australia

12. Telethon Kids Institute and the Division of Paediatrics, Faculty of Helath and Medical Sciences, University of Western Australia, Perth, Australia

13. American College of Medical Genetics and Genomics (ACMG), Bethesda, MD, USA

14. Computational Bioscience Program, University of Colorado Anschutz Medical Campus, Colorado, USA

15. Johns Hopkins University Schools of Medicine, Public Health, and Nursing

16. Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

17. Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA

18. Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, USA

19. Ludwig-Maximilians University, German Center for Lung Research (DZL), Munich, Germany

20. Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria

21. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria

22. Institute for Systems Genomics, University of Connecticut, Farmington, CT 06032, USA

23. INSERM, US14––Orphanet, Plateforme Maladies Rares, Paris, France

24. Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley CA, USA

25. German Centre for Infection Research (DZIF), Munich, Germany

26. Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA

27. FutureNeuro, SFI Research Centre for Chronic and Rare Neurological Diseases, Ireland

28. Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI). Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany

29. Centre for Biobanking FREEZE, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany

30. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367 Belvaux, Luxembourg

31. Translational and Integrative Sciences Center, Department of Environmental and Molecular Toxicology, Oregon State University, OR, USA

32. WA Register of Developmental Anomalies

33. Curtin University, Western Australia, Australia

34. Division of Kidney-Urologic Pathology, Johns Hopkins University, Baltimore, MD 21205, USA

35. SimulConsult, Inc., Chestnut Hill, MA, USA

36. Research Unit for Pediatric Hematology and Immunology, Division of Pediatric Hemato-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria

37. The William Harvey Research Institute, Charterhouse Square Barts and the London School of Medicine and Dentistry Queen Mary University of London, London EC1M 6BQ, UK

38. Genomic Research Department, Emedgene Technologies, Tel Aviv, Israel

39. Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel

40. West Australian Register of Developmental Anomalies, East Perth, WA, Australia

41. Rare Disease Ghana Initiative, Ghana

42. The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, PA, USA

43. Human Genetics, Bioscientia GmbH, Ingelheim, Germany

44. Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

45. The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, USA

Abstract

Abstract The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.

Funder

Monarch R24

NHGRI

NHGRI/NCI

Solve-RD

HIPBI

DFG

E-Rare-3

HCQ4Surfdefect

Cost CA

Publisher

Oxford University Press (OUP)

Subject

Genetics

Reference67 articles.

1. The Human Phenotype Ontology: a tool for annotating and analyzing human hereditary disease;Robinson;Am. J. Hum. Genet.,2008

2. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data;Köhler;Nucleic Acids Res.,2014

3. The Human Phenotype Ontology in 2017;Köhler;Nucleic Acids Res.,2017

4. Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources;Köhler;Nucleic Acids Res.,2018

5. Coverage of phenotypes in standard terminologies;Rainer,2014

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