GenIA: The Genetic Immunology Advisor Database – A Resource made for and by the IEI Community

Abstract

Immunity – the ability to distinguish ‘self’ from ‘non-self’ - exists in some form in every living cell, so its dysregulation harbors far-reaching consequences for every realm of human health. With the advent of increasingly diverse and powerful -omics technologies, the biological space of inborn errors of immunity (IEIs) continues to rapidly expand. Identification of these monogenic or oligogenic conditions has provided valuable insight into basic human immunobiology, not to mention the pathophysiology and treatment of clinical phenocopies with presumed polygenic architectures. However, along with increasing discovery comes increasing dimensionality of both genotypic and phenotypic information, as well as the challenges of diagnosis and management for a disease landscape with so much complexity of mechanism and presentation. There is a pressing need for an easily accessible, expertly curated, comprehensive database on immune-related conditions, that can be useful for a diverse community of stakeholders and remain as collaborative, transparent and institution-agnostic as possible. To this end, we present GenIA, the Genetic Immunology Advisor database, a publicly accessible and manually curated resource providing detailed, multi-dimensional IEI information. Our database strives to balance critical evaluation with comprehensiveness of inclusion – whether documenting paradigms and pitfalls for genetic architectures and disease conditions, or variant- and patient-based clinical, functional and immunophenotyping data. GenIA encompasses significantly more up-to-date IEI knowledge and greater dimensionality than currently existing databases, but without sacrificing level of detail. By focusing in-depth on IEIs, this database is intended to dovetail with rather than replace any of the pre-existing efforts at gene/variant curation such as ClinGen, or large genotype/phenotype databases such as HPO or OMIM – indeed, we have taken steps towards linking collaboratively with them.Our database is not simply a data aggregator – it integrates information with the patient as the linchpin that anchors the extensive allelic, genetic, mechanistic and clinical heterogeneity characteristic of IEIs. This patientcentered data structure is also essential for promoting multi-lateral involvement. We built this platform for diverse stakeholders in the IEI community and hope that all can become both users and contributors.