WiNGS-API: a federated genome/phenome data sharing platform enabling gene discovery and variant classification for rare diseases.

backgroundGenomic research on rare diseases requires large-scale data sharing to identify pathogenic variants. Traditionally, this is achieved through centralized databases that require the physical transfer of genomic data to third-party servers. However, this approach presents significant challenges under data protection frameworks like the General Data Protection Regulation (GDPR), which considers genomic data inherently identifiable and imposes strict limitations on data sharing.

resultsTo address these limitations, WiNGS-API introduces a federated, automated, and privacy-compliant platform that enables variant-level data sharing across institutions without requiring centralized data transfer. WiNGS-API has been deployed in seven centers, managing over 6,400 samples with single-nucleotide variants (SNV) calls, 1,500 with copy number variants (CNVs), and 500 with structural variants (SVs) from long-read sequencing. The system supports sample-based analysis for variant interpretation and automated trio-based filtering, which reduces candidate de novo variants for clinical review. Federated querying, enables the identification of additional carriers and false positives, as well as improved understanding of variants of unknown significance—outcomes not readily achievable with data from a single institution.

conclusionsWiNGS-API bridges the gap between data privacy regulations and genomic collaboration, offering automated variant filtering, annotation, and genotype–phenotype correlation. It provides a scalable solution for multi-center genomic research. WiNGS represents a significant step toward secure, large-scale genomic data sharing, advancing the study of rare diseases while maintaining compliance with ethical and legal standards. WiNGS-API is publicly accessible at https://wings.esat.kuleuven.be/rest-api/api-docs/ .