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      The Human Phenotype Ontology in 2021

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      , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
      Nucleic Acids Research
      Oxford University Press

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          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.

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          ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology

          The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.
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            Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology

            The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of such a revision is to recognize that some seizure types can have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types, and to adopt more transparent names. Because current knowledge is insufficient to form a scientifically based classification, the 2017 Classification is operational (practical) and based on the 1981 Classification, extended in 2010. Changes include the following: (1) "partial" becomes "focal"; (2) awareness is used as a classifier of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated; (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional; (5) atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset; (6) focal to bilateral tonic-clonic seizure replaces secondarily generalized seizure; (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic; and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types.
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              Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee

              We report the updated classification of Inborn Errors of Immunity/Primary Immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 430 inborn errors of immunity, including 64 gene defects that have either been discovered in the past 2 years since the previous update (published January 2018) or were characterized earlier but have since been confirmed or expanded upon in subsequent studies. The application of next-generation sequencing continues to expedite the rapid identification of novel gene defects, rare or common; broaden the immunological and clinical phenotypes of conditions arising from known gene defects and even known variants; and implement gene-specific therapies. These advances are contributing to greater understanding of the molecular, cellular, and immunological mechanisms of disease, thereby enhancing immunological knowledge while improving the management of patients and their families. This report serves as a valuable resource for the molecular diagnosis of individuals with heritable immunological disorders and also for the scientific dissection of cellular and molecular mechanisms underlying inborn errors of immunity and related human diseases.
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                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                08 January 2021
                02 December 2020
                02 December 2020
                : 49
                : D1
                : D1207-D1217
                Affiliations
                Ada Health GmbH , Berlin, Germany
                Monarch Initiative
                Monarch Initiative
                The Jackson Laboratory for Genomic Medicine , Farmington, CT, USA
                Monarch Initiative
                Semanticly Ltd , London, UK
                European Bioinformatics Institute (EMBL-EBI)
                Monarch Initiative
                The Jackson Laboratory for Genomic Medicine , Farmington, CT, USA
                Translational and Clinical Research Institute, Newcastle University , Newcastle upon Tyne, UK
                Clinical Neurosciences, Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne, UK
                Monarch Initiative
                Oregon Clinical & Translational Research Institute, Oregon Health & Science University
                Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa , Genoa, Italy
                Pediatric Neurology and Muscular Diseases Unit, IRCCS ‘G. Gaslini’ Institute , Genoa, Italy
                Western Australian Register of Developmental Anomalies, King Edward memorial Hospital , Perth, Australia
                Telethon Kids Institute and the Division of Paediatrics, Faculty of Helath and Medical Sciences, University of Western Australia , Perth, Australia
                American College of Medical Genetics and Genomics (ACMG) , Bethesda, MD, USA
                Computational Bioscience Program, University of Colorado Anschutz Medical Campus , Colorado, USA
                Johns Hopkins University Schools of Medicine, Public Health, and Nursing
                Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München , Munich, Germany
                Division of Neurology, Children's Hospital of Philadelphia , Philadelphia, PA, USA
                Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia , Philadelphia, PA, USA
                Division of Neurology, Children's Hospital of Philadelphia , Philadelphia, PA, USA
                Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia , Philadelphia, PA, USA
                Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München , Munich, Germany
                Ludwig-Maximilians University, German Center for Lung Research (DZL) , Munich, Germany
                Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases , Vienna, Austria
                CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , Vienna, Austria
                Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases , Vienna, Austria
                CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , Vienna, Austria
                Institute for Systems Genomics, University of Connecticut , Farmington, CT 06032, USA
                INSERM, US14––Orphanet, Plateforme Maladies Rares , Paris, France
                Monarch Initiative
                Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory , Berkeley CA, USA
                American College of Medical Genetics and Genomics (ACMG) , Bethesda, MD, USA
                Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München , Munich, Germany
                Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München , Munich, Germany
                German Centre for Infection Research (DZIF) , Munich, Germany
                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
                Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München , Munich, Germany
                FutureNeuro, SFI Research Centre for Chronic and Rare Neurological Diseases , Ireland
                Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI). Faculty of Medicine, Medical Center - University of Freiburg , Freiburg, Germany
                Centre for Biobanking FREEZE, Faculty of Medicine, Medical Center - University of Freiburg , Freiburg, Germany
                Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München , Munich, Germany
                Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München , Munich, Germany
                Ludwig-Maximilians University, German Center for Lung Research (DZL) , Munich, Germany
                Luxembourg Centre for Systems Biomedicine, University of Luxembourg , L-4367 Belvaux, Luxembourg
                INSERM, US14––Orphanet, Plateforme Maladies Rares , Paris, France
                Monarch Initiative
                Translational and Integrative Sciences Center, Department of Environmental and Molecular Toxicology, Oregon State University , OR, USA
                American College of Medical Genetics and Genomics (ACMG) , Bethesda, MD, USA
                Monarch Initiative
                Translational and Integrative Sciences Center, Department of Environmental and Molecular Toxicology, Oregon State University , OR, USA
                American College of Medical Genetics and Genomics (ACMG) , Bethesda, MD, USA
                Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München , Munich, Germany
                Ludwig-Maximilians University, German Center for Lung Research (DZL) , Munich, Germany
                INSERM, US14––Orphanet, Plateforme Maladies Rares , Paris, France
                WA Register of Developmental Anomalies
                Curtin University , Western Australia, Australia
                Division of Kidney-Urologic Pathology, Johns Hopkins University , Baltimore, MD 21205, USA
                SimulConsult, Inc. , Chestnut Hill, MA, USA
                Research Unit for Pediatric Hematology and Immunology, Division of Pediatric Hemato-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz , Graz, Austria
                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
                Genomic Research Department, Emedgene Technologies , Tel Aviv, Israel
                Faculty of Medicine, Hebrew University Hadassah Medical School , Jerusalem, Israel
                West Australian Register of Developmental Anomalies , East Perth, WA, Australia
                Rare Disease Ghana Initiative , Ghana
                Division of Neurology, Children's Hospital of Philadelphia , Philadelphia, PA, USA
                The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , PA, USA
                Human Genetics , Bioscientia GmbH, Ingelheim, Germany
                Department of Neurology, University of Pennsylvania, Perelman School of Medicine , Philadelphia, PA, USA
                The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA, USA
                Monarch Initiative
                Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory , Berkeley CA, USA
                Monarch Initiative
                Oregon Clinical & Translational Research Institute, Oregon Health & Science University
                Translational and Integrative Sciences Center, Department of Environmental and Molecular Toxicology, Oregon State University , OR, USA
                Monarch Initiative
                The Jackson Laboratory for Genomic Medicine , Farmington, CT, USA
                Institute for Systems Genomics, University of Connecticut , Farmington, CT 06032, USA
                Author notes
                To whom correspondence should be addressed. Tel: +1 860 837 2095; Email: peter.robinson@ 123456jax.org
                Author information
                http://orcid.org/0000-0003-2356-950X
                http://orcid.org/0000-0002-0736-9199
                Article
                gkaa1043
                10.1093/nar/gkaa1043
                7778952
                33264411
                2e1ce242-0a83-4d37-ae00-83c33fa83c5c
                © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 November 2020
                : 11 October 2020
                : 17 September 2020
                Page count
                Pages: 11
                Funding
                Funded by: Monarch R24;
                Award ID: 2R24OD011883-05A1
                Funded by: NHGRI, DOI 10.13039/100000051;
                Award ID: 1RM1HG010860
                Funded by: NHGRI/NCI;
                Award ID: 5U13CA221044
                Funded by: Solve-RD;
                Award ID: 779257
                Funded by: HIPBI;
                Award ID: 643578
                Funded by: DFG, DOI 10.13039/501100001659;
                Award ID: Gr 970/9-1
                Funded by: E-Rare-3;
                Funded by: HCQ4Surfdefect;
                Funded by: Cost CA;
                Award ID: 16125 ENTeR-chILD
                Categories
                AcademicSubjects/SCI00010
                Database Issue

                Genetics
                Genetics

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