A corpus of GA4GH phenopackets: Case-level phenotyping for genomic diagnostics and discovery

Daniel Danis; Michael J Bamshad; Yasemin Bridges; Andrés Caballero-Oteyza; Pilar Cacheiro; Leigh C Carmody; Leonardo Chimirri; Jessica X Chong; Ben Coleman; Raymond Dalgleish; Peter J Freeman; Adam S L Graefe; Tudor Groza; Peter Hansen; Julius O B Jacobsen; Adam Klocperk; Maaike Kusters; Markus S Ladewig; Anthony J Marcello; Teresa Mattina; Christopher J Mungall; Monica C Munoz-Torres; Justin T Reese; Filip Rehburg; Bárbara C S Reis; Catharina Schuetz; Damian Smedley; Timmy Strauss; Jagadish Chandrabose Sundaramurthi; Sylvia Thun; Kyran Wissink; John F Wagstaff; David Zocche; Melissa A Haendel; Peter N Robinson

doi:10.1016/j.xhgg.2024.100371

A corpus of GA4GH phenopackets: Case-level phenotyping for genomic diagnostics and discovery

HGG Adv. 2024 Oct 10;6(1):100371. doi: 10.1016/j.xhgg.2024.100371. Online ahead of print.

Authors

Daniel Danis¹, Michael J Bamshad², Yasemin Bridges³, Andrés Caballero-Oteyza⁴, Pilar Cacheiro³, Leigh C Carmody⁵, Leonardo Chimirri⁶, Jessica X Chong⁷, Ben Coleman⁵, Raymond Dalgleish⁸, Peter J Freeman⁹, Adam S L Graefe⁶, Tudor Groza¹⁰, Peter Hansen⁶, Julius O B Jacobsen³, Adam Klocperk¹¹, Maaike Kusters¹², Markus S Ladewig¹³, Anthony J Marcello¹⁴, Teresa Mattina¹⁵, Christopher J Mungall¹⁶, Monica C Munoz-Torres¹⁷, Justin T Reese¹⁶, Filip Rehburg⁶, Bárbara C S Reis¹⁸, Catharina Schuetz¹⁹, Damian Smedley³, Timmy Strauss²⁰, Jagadish Chandrabose Sundaramurthi⁵, Sylvia Thun⁶, Kyran Wissink²¹, John F Wagstaff⁸, David Zocche²², Melissa A Haendel²³, Peter N Robinson²⁴

Affiliations

¹ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington CT 06032, USA.
² Department of Pediatrics, Division of Genetic Medicine, University of Washington, 1959 NE Pacific Street, Box 357371, Seattle, WA 98195, USA; Brotman-Baty Institute for Precision Medicine, 1959 NE Pacific Street, Box 357657, Seattle, WA 98195, USA; Department of Pediatrics, Division of Genetic Medicine, Seattle Children's Hospital, Seattle, WA 98195, USA.
³ William Harvey Research Institute, Queen Mary University of London, London, UK.
⁴ Clinic for Immunology and Rheumatology, Hanover Medical School, Hanover, Germany; RESiST-Cluster of Excellence 2155, Hanover Medical School, Hanover, Germany.
⁵ The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington CT 06032, USA.
⁶ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁷ Department of Pediatrics, Division of Genetic Medicine, University of Washington, 1959 NE Pacific Street, Box 357371, Seattle, WA 98195, USA; Brotman-Baty Institute for Precision Medicine, 1959 NE Pacific Street, Box 357657, Seattle, WA 98195, USA.
⁸ Department of Genetics, Genomics and Cancer Sciences, University of Leicester, Leicester, UK.
⁹ Division of Informatics, Imaging and Data Science, The University of Manchester, Manchester, UK.
¹⁰ Rare Care Centre, Perth Children's Hospital, Nedlands, WA 6009, Australia; SingHealth Duke-NUS Institute of Precision Medicine, 5 Hospital Drive Level 9, Singapore 169609, Singapore; Telethon Kids Institute, Nedlands, WA 6009, Australia.
¹¹ Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic.
¹² Department of Paediatric Immunology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; University College London Institute of Child Health, London, UK.
¹³ Department of Ophthalmology, University Clinic Marburg - Campus Fulda, Fulda, Germany.
¹⁴ Department of Pediatrics, Division of Genetic Medicine, University of Washington, 1959 NE Pacific Street, Box 357371, Seattle, WA 98195, USA.
¹⁵ Medica Genetics University of Catania Italy, Catania, Italy; Morgagni Foundation and Clinic, Catania, Italy.
¹⁶ Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
¹⁷ Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹⁸ Department of Allergy and Immunology, National Institute of Women's, Children's and Adolescents' Health Fernandes Figueira, Rio de Janeiro, Brazil; High Complexity Laboratory, National Institute of Women's, Children's and Adolescents' Health Fernandes Figueira, Rio de Janeiro, Brazil.
¹⁹ Department of Pediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; University Center for Rare Diseases, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Center for Child and Adolescent Health (DZKJ), partner site Leipzig/Dresden, Dresden, Germany.
²⁰ Department of Pediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; University Center for Rare Diseases, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
²¹ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; Utrecht University, Utrecht, the Netherlands.
²² North West Thames Regional Genetics Service, Northwick Park & St Mark's Hospitals, London, UK.
²³ University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²⁴ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany; The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington CT 06032, USA; ELLIS-European Laboratory for Learning and Intelligent Systems. Electronic address: peter.robinson@bih-charite.de.

Abstract

The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present Phenopacket Store. Phenopacket Store v.0.1.19 includes 6,668 phenopackets representing 475 Mendelian and chromosomal diseases associated with 423 genes and 3,834 unique pathogenic alleles curated from 959 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.

Keywords: global alliance for genomics and health; human phenotype ontology; phenopacket schema.