{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:50:18Z","timestamp":1790362218477,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Elixir Belgium","award":["FWO\/IRI I000323N"],"award-info":[{"award-number":["FWO\/IRI I000323N"]}]},{"name":"Elixir Belgium","award":["FWO\/IRI I000323N"],"award-info":[{"award-number":["FWO\/IRI I000323N"]}]},{"name":"Collaborative Doctoral Partnership Agreement of the Joint Research Center","award":["F.7\/KU LEUVEN B&G 35332"],"award-info":[{"award-number":["F.7\/KU LEUVEN B&G 35332"]}]},{"name":"KULeuven","award":["C1-C14\/18\/092"],"award-info":[{"award-number":["C1-C14\/18\/092"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"DOI":"10.1186\/s13073-026-01627-9","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T08:28:53Z","timestamp":1774513733000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["WiNGS-API: a federated genome\/phenome data sharing platform enabling gene discovery and variant classification for rare diseases"],"prefix":"10.1186","volume":"18","author":[{"given":"Nishkala","family":"Sattanathan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Huremagic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris Robert","family":"Vermeesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Moreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Vandeweyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"1627_CR1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13073-020-00748-z","volume":"12","author":"CR Marshall","year":"2020","unstructured":"Marshall CR, Bick D, Belmont JW, Taylor SL, Ashley E, Dimmock D, et al. The Medical Genome Initiative: moving whole-genome sequencing for rare disease diagnosis to the clinic. Genome Med. 2020;12:48. https:\/\/doi.org\/10.1186\/s13073-020-00748-z.","journal-title":"Genome Med"},{"key":"1627_CR2","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1038\/s41436-019-0554-6","volume":"21","author":"S Srivastava","year":"2019","unstructured":"Srivastava S, Love-Nichols JA, Dies KA, Ledbetter DH, Martin CL, Chung WK, et al. Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet Med. 2019;21:2413\u201321. https:\/\/doi.org\/10.1038\/s41436-019-0554-6.","journal-title":"Genet Med"},{"key":"1627_CR3","doi-asserted-by":"publisher","unstructured":"Katsanis N. The oligogenic properties of Bardet-Biedl syndrome. Hum Mol Genet. 2004;R65\u201371. https:\/\/doi.org\/10.1093\/hmg\/ddh092. 13 Spec 1.","DOI":"10.1093\/hmg\/ddh092"},{"key":"1627_CR4","doi-asserted-by":"publisher","unstructured":"Rahit KMTH, Tarailo-Graovac M. Genetic modifiers and rare mendelian disease. Genes. 2020;11. https:\/\/doi.org\/10.3390\/genes11030239.","DOI":"10.3390\/genes11030239"},{"key":"1627_CR5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ajhg.2022.12.004","volume":"110","author":"CM Wilczewski","year":"2023","unstructured":"Wilczewski CM, Obasohan J, Paschall JE, Zhang S, Singh S, Maxwell GL, et al. Genotype first: Clinical genomics research through a reverse phenotyping approach. Am J Hum Genet. 2023;110:3\u201312. https:\/\/doi.org\/10.1016\/j.ajhg.2022.12.004.","journal-title":"Am J Hum Genet"},{"key":"1627_CR6","doi-asserted-by":"publisher","unstructured":"Canakoglu A, Pinoli P, Gulino A, Nanni L, Masseroli M, Ceri S. Federated sharing and processing of genomic datasets for tertiary data analysis. Brief Bioinf. 2021;22. https:\/\/doi.org\/10.1093\/bib\/bbaa091.","DOI":"10.1093\/bib\/bbaa091"},{"key":"1627_CR7","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/s41436-019-0646-3","volume":"22","author":"KD Mandl","year":"2020","unstructured":"Mandl KD, Glauser T, Krantz ID, Avillach P, Bartels A, Beggs AH, et al. The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning system. Genet Med. 2020;22:371\u201380. https:\/\/doi.org\/10.1038\/s41436-019-0646-3.","journal-title":"Genet Med"},{"key":"1627_CR8","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1002\/humu.22858","volume":"36","author":"AA Philippakis","year":"2015","unstructured":"Philippakis AA, Azzariti DR, Beltran S, Brookes AJ, Brownstein CA, Brudno M, et al. The Matchmaker Exchange: a platform for rare disease gene discovery. Hum Mutat. 2015;36:915\u201321. https:\/\/doi.org\/10.1002\/humu.22858.","journal-title":"Hum Mutat"},{"key":"1627_CR9","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1002\/humu.24369","volume":"43","author":"J Rambla","year":"2022","unstructured":"Rambla J, Baudis M, Ariosa R, Beck T, Fromont LA, Navarro A, et al. Beacon v2 and Beacon networks: A lingua franca for federated data discovery in biomedical genomics, and beyond. Hum Mutat. 2022;43:791\u20139. https:\/\/doi.org\/10.1002\/humu.24369.","journal-title":"Hum Mutat"},{"key":"1627_CR10","doi-asserted-by":"publisher","DOI":"10.1101\/2022.06.23.497325","author":"H Chizari","year":"2022","unstructured":"Chizari H, Sattanathan N, Ardeshirdavani A, Shabani N, Huremagic B, Vermeesch JR, et al. WiNGS: Widely integrated NGS platform for federated genome analysis. BioRxiv. 2022. https:\/\/doi.org\/10.1101\/2022.06.23.497325.","journal-title":"BioRxiv"},{"key":"1627_CR11","doi-asserted-by":"publisher","unstructured":"Casaletto J, Bernier A, McDougall R, Cline MS. Annu Rev Genomics Hum Genet. 2023;24:347\u201368. https:\/\/doi.org\/10.1146\/annurev-genom-110122-084756. Federated Analysis for Privacy-Preserving Data Sharing: A Technical and Legal Primer.","DOI":"10.1146\/annurev-genom-110122-084756"},{"key":"1627_CR12","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.jbi.2016.10.015","volume":"64","author":"WL Schulz","year":"2016","unstructured":"Schulz WL, Nelson BG, Felker DK, Durant TJS, Torres R. Evaluation of relational and NoSQL database architectures to manage genomic annotations. J Biomed Inf. 2016;64:288\u201395. https:\/\/doi.org\/10.1016\/j.jbi.2016.10.015.","journal-title":"J Biomed Inf"},{"key":"1627_CR13","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","volume":"17","author":"W McLaren","year":"2016","unstructured":"McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GRS, Thormann A, et al. The ensembl variant effect predictor. Genome Biol. 2016;17:122. https:\/\/doi.org\/10.1186\/s13059-016-0974-4.","journal-title":"Genome Biol"},{"key":"1627_CR14","doi-asserted-by":"publisher","first-page":"D212","DOI":"10.1093\/nar\/gkaa921","volume":"49","author":"C RNAcentral","year":"2021","unstructured":"RNAcentral C. RNAcentral 2021: secondary structure integration, improved sequence search and new member databases. Nucleic Acids Res. 2021;49:D212\u201320. https:\/\/doi.org\/10.1093\/nar\/gkaa921.","journal-title":"Nucleic Acids Res"},{"key":"1627_CR15","doi-asserted-by":"publisher","first-page":"D886","DOI":"10.1093\/nar\/gky1016","volume":"47","author":"P Rentzsch","year":"2019","unstructured":"Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2019;47:D886\u201394. https:\/\/doi.org\/10.1093\/nar\/gky1016.","journal-title":"Nucleic Acids Res"},{"key":"1627_CR16","doi-asserted-by":"publisher","first-page":"3572","DOI":"10.1093\/bioinformatics\/bty304","volume":"34","author":"V Geoffroy","year":"2018","unstructured":"Geoffroy V, Herenger Y, Kress A, Stoetzel C, Piton A, Dollfus H, et al. AnnotSV: an integrated tool for structural variations annotation. Bioinformatics. 2018;34:3572\u20134. https:\/\/doi.org\/10.1093\/bioinformatics\/bty304.","journal-title":"Bioinformatics"},{"key":"1627_CR17","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1038\/s41587-023-02024-y","volume":"42","author":"M Smolka","year":"2024","unstructured":"Smolka M, Paulin LF, Grochowski CM, Horner DW, Mahmoud M, Behera S, et al. Detection of mosaic and population-level structural variants with Sniffles2. Nat Biotechnol. 2024;42:1571\u201380. https:\/\/doi.org\/10.1038\/s41587-023-02024-y.","journal-title":"Nat Biotechnol"},{"key":"1627_CR18","unstructured":"European Medicines Agency. DARWIN EU\u00ae - Age - specific incidence rates of RSV - related disease in Europe. 2024 [cited 30 Nov 2025]. Available: https:\/\/catalogues.ema.europa.eu\/system\/files\/2024-06\/DARWIN_EU_D2.2.4_Report_P2-C1-011_RSV_v2.2_Public.pdf"},{"key":"1627_CR19","doi-asserted-by":"publisher","first-page":"e54332","DOI":"10.2196\/54332","volume":"5","author":"M Thomas","year":"2024","unstructured":"Thomas M, Mackes N, Preuss-Dodhy A, Wieland T, Bundschus M. Assessing privacy vulnerabilities in genetic data sets: scoping review. JMIR Bioinform Biotech. 2024;5:e54332. https:\/\/doi.org\/10.2196\/54332.","journal-title":"JMIR Bioinform Biotech"},{"key":"1627_CR20","doi-asserted-by":"publisher","unstructured":"Saleem K, Cicek AE, Sav S. Beacon Reconstruction Attack: Reconstruction of genomes in genomic data-sharing beacons using summary statistics. Bioinformatics. 2025;41. https:\/\/doi.org\/10.1093\/bioinformatics\/btaf273.","DOI":"10.1093\/bioinformatics\/btaf273"},{"key":"1627_CR21","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1101\/gr.279273.124","volume":"34","author":"JA Gustafson","year":"2024","unstructured":"Gustafson JA, Gibson SB, Damaraju N, Zalusky MPG, Hoekzema K, Twesigomwe D, et al. High-coverage nanopore sequencing of samples from the 1000 Genomes Project to build a comprehensive catalog of human genetic variation. Genome Res. 2024;34:2061\u201373. https:\/\/doi.org\/10.1101\/gr.279273.124.","journal-title":"Genome Res"},{"key":"1627_CR22","doi-asserted-by":"publisher","first-page":"160025","DOI":"10.1038\/sdata.2016.25","volume":"3","author":"JM Zook","year":"2016","unstructured":"Zook JM, Catoe D, McDaniel J, Vang L, Spies N, Sidow A, et al. Extensive sequencing of seven human genomes to characterize benchmark reference materials. Sci Data. 2016;3:160025. https:\/\/doi.org\/10.1038\/sdata.2016.25.","journal-title":"Sci Data"},{"key":"1627_CR23","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/ejhg.2016.133","volume":"25","author":"S El Chehadeh","year":"2017","unstructured":"El Chehadeh S, Kerstjens-Frederikse WS, Thevenon J, Kuentz P, Bruel A-L, Thauvin-Robinet C, et al. Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature. Eur J Hum Genet. 2017;25:43\u201351. https:\/\/doi.org\/10.1038\/ejhg.2016.133.","journal-title":"Eur J Hum Genet"},{"key":"1627_CR24","doi-asserted-by":"publisher","first-page":"5910","DOI":"10.1038\/s41467-021-25972-y","volume":"12","author":"D Froelicher","year":"2021","unstructured":"Froelicher D, Troncoso-Pastoriza JR, Raisaro JL, Cuendet MA, Sousa JS, Cho H, et al. Truly privacy-preserving federated analytics for precision medicine with multiparty homomorphic encryption. Nat Commun. 2021;12:5910. https:\/\/doi.org\/10.1038\/s41467-021-25972-y.","journal-title":"Nat Commun"},{"key":"1627_CR25","doi-asserted-by":"publisher","unstructured":"Kumar AV, Monica K, Mandadi K. Data Privacy Over Cloud Computing using Multi Party Computation. 2023 International Conference on Intelligent Data Communication Technologies and Internet of Things (IDCIoT). IEEE; 2023. pp. 262\u2013267. https:\/\/doi.org\/10.1109\/IDCIoT56793.2023.10053427","DOI":"10.1109\/IDCIoT56793.2023.10053427"},{"key":"1627_CR26","doi-asserted-by":"publisher","unstructured":"Cummings R, Desfontaines D, Evans D, Geambasu R, Huang Y, Jagielski M, et al. Advancing Differential Privacy: Where We Are Now and Future Directions for Real-World Deployment. Harv Data Sci Rev. 2024;6. https:\/\/doi.org\/10.1162\/99608f92.d3197524.","DOI":"10.1162\/99608f92.d3197524"},{"key":"1627_CR27","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1146\/annurev-statistics-060116-054123","volume":"4","author":"C Dwork","year":"2017","unstructured":"Dwork C, Smith A, Steinke T, Ullman J. Exposed! A survey of attacks on private data. Annu Rev Stat Appl. 2017;4:61\u201384. https:\/\/doi.org\/10.1146\/annurev-statistics-060116-054123.","journal-title":"Annu Rev Stat Appl"},{"key":"1627_CR28","doi-asserted-by":"publisher","unstructured":"Shabani M, Marelli L. EMBO Rep. 2019;20. https:\/\/doi.org\/10.15252\/embr.201948316. Re-identifiability of genomic data and the GDPR: Assessing the re-identifiability of genomic data in light of the EU General Data Protection Regulation.","DOI":"10.15252\/embr.201948316"},{"key":"1627_CR29","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.ajhg.2015.09.010","volume":"97","author":"SS Shringarpure","year":"2015","unstructured":"Shringarpure SS, Bustamante CD. Privacy Risks from Genomic Data-Sharing Beacons. Am J Hum Genet. 2015;97:631\u201346. https:\/\/doi.org\/10.1016\/j.ajhg.2015.09.010.","journal-title":"Am J Hum Genet"},{"key":"1627_CR30","doi-asserted-by":"publisher","first-page":"e1000167","DOI":"10.1371\/journal.pgen.1000167","volume":"4","author":"N Homer","year":"2008","unstructured":"Homer N, Szelinger S, Redman M, Duggan D, Tembe W, Muehling J, et al. Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays. PLoS Genet. 2008;4:e1000167. https:\/\/doi.org\/10.1371\/journal.pgen.1000167.","journal-title":"PLoS Genet"},{"key":"1627_CR31","doi-asserted-by":"publisher","first-page":"761","DOI":"10.17269\/s41997-020-00303-8","volume":"111","author":"K Wilkinson","year":"2020","unstructured":"Wilkinson K, Green C, Nowicki D, Von Schindler C. Less than five is less than ideal: replacing the less than 5 cell size rule with a risk-based data disclosure protocol in a public health setting. Can J Public Health. 2020;111:761\u20135. https:\/\/doi.org\/10.17269\/s41997-020-00303-8.","journal-title":"Can J Public Health"},{"key":"1627_CR32","doi-asserted-by":"publisher","unstructured":"Angulo E, M\u00e1rquez J, Villanueva-Polanco R. Training of classification models via federated learning and homomorphic encryption. Sensors. 2023;23. https:\/\/doi.org\/10.3390\/s23041966.","DOI":"10.3390\/s23041966"},{"key":"1627_CR33","doi-asserted-by":"publisher","first-page":"e33720","DOI":"10.2196\/33720","volume":"24","author":"S Kavianpour","year":"2022","unstructured":"Kavianpour S, Sutherland J, Mansouri-Benssassi E, Coull N, Jefferson E. Next-Generation Capabilities in Trusted Research Environments: Interview Study. J Med Internet Res. 2022;24:e33720. https:\/\/doi.org\/10.2196\/33720.","journal-title":"J Med Internet Res"},{"key":"1627_CR34","unstructured":"Vandeweyer G, Sattanathan N, Huremagic B. WiNGS project readme and repositories v1.0 Github. https:\/\/github.com\/wings-public"},{"key":"1627_CR35","doi-asserted-by":"publisher","unstructured":"Vandeweyer G, Sattanathan N, Huremagic B. WiNGS project readme and repositories (v1.0). Zenodo. https:\/\/doi.org\/10.5281\/zenodo.18480125.","DOI":"10.5281\/zenodo.18480125"},{"key":"1627_CR36","doi-asserted-by":"publisher","unstructured":"Sattanathan N, Huremagic B. wings-public\/wings_rest_api: WiNGS REST API (v1.0). Zenodo. https:\/\/doi.org\/10.5281\/zenodo.18480351.","DOI":"10.5281\/zenodo.18480351"}],"container-title":["Genome Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13073-026-01627-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01627-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01627-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:16:57Z","timestamp":1775128617000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13073-026-01627-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1627"],"URL":"https:\/\/doi.org\/10.1186\/s13073-026-01627-9","relation":{},"ISSN":["1756-994X"],"issn-type":[{"value":"1756-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]},"assertion":[{"value":"16 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Ethical committee research UZ\/KU Leuven (S65304 \u2013 S65991) and informed consent was obtained from all participants to participate. This study conformed with the principles of the Helsinki Declaration. Secondary use of WES\/WGS data is approved by EC approvals number 13\/1\/12 and by approval for Project ID 7746 - EDGE 004350 from the Antwerp University Hospital Ethical Committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from all participants for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37"}}