GenIA, the Genetic Immunology Advisor database for inborn errors of immunity

Andrés Caballero-Oteyza; Laura Crisponi; Xiao P Peng; Kevin Yauy; Stefano Volpi; Stefano Giardino; Alexandra F Freeman; Bodo Grimbacher; Michele Proietti

doi:10.1016/j.jaci.2023.11.022

GenIA, the Genetic Immunology Advisor database for inborn errors of immunity

J Allergy Clin Immunol. 2024 Mar;153(3):831-843. doi: 10.1016/j.jaci.2023.11.022. Epub 2023 Nov 30.

Authors

Andrés Caballero-Oteyza¹, Laura Crisponi², Xiao P Peng³, Kevin Yauy⁴, Stefano Volpi⁵, Stefano Giardino⁶, Alexandra F Freeman⁷, Bodo Grimbacher⁸, Michele Proietti⁹

Affiliations

¹ Clinic for Immunology and Rheumatology, Hanover Medical School, Hanover, Germany; RESiST-Cluster of Excellence 2155, Hanover Medical School, Hanover, Germany; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany. Electronic address: andres.caballero@uniklinik-freiburg.de.
² Institute for Genetic and Biomedical Research, The National Research Council, Monserrato, Cagliari, Italy.
³ Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Md.
⁴ University of Montpellier, LIRMM, CNRS, Reference Center for Congenital Anomalies, Clinical Genetic Unit, Montpellier University Hospital Center, Montpellier, France.
⁵ Center for Autoinflammatory Diseases and Immunodeficiencies, Pediatric Rheumatology Clinic, IRCCS Istituto Giannina Gaslini, Genova, and DINOGMI, Università degli Studi di Genova, Genova, Italy.
⁶ Hematopoietic Stem Cell Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy.
⁷ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
⁸ Institute for Immunodeficiency, Center for Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany; Clinic of Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs University of Freiburg, Freiburg, Germany; RESiST-Cluster of Excellence 2155, Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany; German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany; Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany.
⁹ Clinic for Immunology and Rheumatology, Hanover Medical School, Hanover, Germany; RESiST-Cluster of Excellence 2155, Hanover Medical School, Hanover, Germany; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany. Electronic address: michele.proietti@uniklinik-freiburg.de.

PMID: 38040041
DOI: 10.1016/j.jaci.2023.11.022

Abstract

Background: To date, no publicly accessible platform has captured and synthesized all of the layered dimensions of genotypic, phenotypic, and mechanistic information published in the field of inborn errors of immunity (IEIs). Such a platform would represent the extensive and complex landscape of IEIs and could increase the rate of diagnosis in patients with a suspected IEI, which remains unacceptably low.

Objective: Our aim was to create an expertly curated, patient-centered, multidimensional IEI database that enables aggregation and sophisticated data interrogation and promotes involvement from diverse stakeholders across the community.

Methods: The database structure was designed following a subject-centered model and written in Structured Query Language (SQL). The web application is written in Hypertext Preprocessor (PHP), Hypertext Markup Language (HTML), Cascading Style Sheets (CSS), and JavaScript. All data stored in the Genetic Immunology Advisor (GenIA) are extracted by manually reviewing published research articles.

Results: We completed data collection and curation for 24 pilot genes. Using these data, we have exemplified how GenIA can provide quick access to structured, longitudinal, more thorough, comprehensive, and up-to-date IEI knowledge than do currently existing databases, such as ClinGen, Human Phenotype Ontology (HPO), ClinVar, or Online Mendelian Inheritance in Man (OMIM), with which GenIA intends to dovetail.

Conclusions: GenIA strives to accurately capture the extensive genetic, mechanistic, and phenotypic heterogeneity found across IEIs, as well as genetic paradigms and diagnostic pitfalls associated with individual genes and conditions. The IEI community's involvement will help promote GenIA as an enduring resource that supports and improves knowledge sharing, research, diagnosis, and care for patients with genetic immune disease.

Keywords: Inborn error of immunity; curation; database; genetic paradigms; genotype-phenotype; immune disease; immunogenetics; natural history; patient-centered; resource.

MeSH terms

Databases, Genetic*
Humans
Software*