RareLink: scalable REDCap-based framework for rare disease interoperability linking international registries to FHIR and Phenopackets

Adam S L Graefe; Filip Rehburg; Samer Alkarkoukly; Daniel Danis; Ana Grönke; Miriam R Hübner; Alexander Bartschke; Thomas Debertshäuser; Sophie A I Klopfenstein; Julian Saß; Julia Fleck; Mirko Rehberg; Jana Zschüntzsch; Elisabeth F Nyoungui; Tatiana Kalashnikova; Luis Murguía-Favela; Beata Derfalvi; Nicola A M Wright; Shahida Moosa; Soichi Ogishima; Oliver Semler; Susanna Wiegand; Peter Kühnen; Christopher J Mungall; Melissa A Haendel; Peter N Robinson; Sylvia Thun; Oya Beyan

doi:10.1038/s41525-025-00534-z

RareLink: scalable REDCap-based framework for rare disease interoperability linking international registries to FHIR and Phenopackets

NPJ Genom Med. 2025 Nov 18;10(1):72. doi: 10.1038/s41525-025-00534-z.

Authors

Adam S L Graefe^{1

2}, Filip Rehburg³, Samer Alkarkoukly⁴, Daniel Danis³, Ana Grönke⁴, Miriam R Hübner³, Alexander Bartschke³, Thomas Debertshäuser³, Sophie A I Klopfenstein³, Julian Saß³, Julia Fleck⁵, Mirko Rehberg⁶, Jana Zschüntzsch⁷, Elisabeth F Nyoungui⁸, Tatiana Kalashnikova^{9

10}, Luis Murguía-Favela^{9

10}, Beata Derfalvi¹¹, Nicola A M Wright^{9

10}, Shahida Moosa^{12

13}, Soichi Ogishima^{14

15}, Oliver Semler⁶, Susanna Wiegand^{16

17}, Peter Kühnen^{16

18

19}, Christopher J Mungall²⁰, Melissa A Haendel²¹, Peter N Robinson^{3

22}, Sylvia Thun³, Oya Beyan^{23

24}

Affiliations

¹ Berlin Institute of Health at Charité‒Universitätsmedizin Berlin, Berlin, Germany. adam.graefe@charite.de.
² Institute for Biomedical Informatics, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. adam.graefe@charite.de.
³ Berlin Institute of Health at Charité‒Universitätsmedizin Berlin, Berlin, Germany.
⁴ Medical Data Integration Center (MeDIC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
⁵ Center for Rare Diseases, Medical Faculty, RWTH Aachen University, Aachen, Germany.
⁶ Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany, Cologne, Germany.
⁷ Department of Neurology, University Medical Center Goettingen, Goettingen, Germany.
⁸ Department of Medical Informatics, University Medical Center Goettingen, Goettingen, Germany.
⁹ Section of Hematology and Immunology, Alberta Children's Hospital, Calgary, Canada.
¹⁰ University of Calgary, Calgary, Canada.
¹¹ Department of Pediatrics, Division of Immunology, Dalhousie University, IWK Health, Halifax, NS, Canada.
¹² Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa.
¹³ Medical Genetics, Tygerberg Hospital, Cape Town, South Africa.
¹⁴ INGEM, Tohoku University, Sendai, Miyagi, Japan.
¹⁵ Department of Informatics for Genomic Medicine, ToMMo, Tohoku University, Sendai, Miyagi, Japan.
¹⁶ Department of Pediatric Endocrinology and Diabetology, Charité University Hospital, Berlin, Germany.
¹⁷ Center for Chronically Sick Children, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹⁸ Berlin Center for Rare Diseases-Charité University Hospital, Berlin, Germany.
¹⁹ Deutsches Zentrum für Kinder- und Jugendgesundheit (DZKJ), partner site Berlin, Berlin, Germany.
²⁰ Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
²¹ Department of Genetics, University of North Carolina Chapel Hill, Chapel Hill, NC, USA.
²² The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
²³ Institute for Biomedical Informatics, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
²⁴ Fraunhofer Institute for Applied Information Technology, Sankt Augustin, Germany.

Abstract

While Research Electronic Data Capture (REDCap) is widely adopted in rare disease research, its unconstrained data format often lacks native interoperability with global health standards, limiting secondary use. We developed RareLink, an open-source framework implementing our published ontology-based rare disease common data model. It enables standardised data exchange between REDCap, international registries, and downstream analysis tools by linking Global Alliance for Genomics and Health Phenopackets and Health Level 7 Fast Healthcare Interoperability Resources (FHIR) instances conforming to International Patient Summary and Genomics Reporting profiles. RareLink was developed in three phases across Germany, Canada, South Africa, and Japan for registry and data analysis purposes. We defined a simulated Kabuki syndrome cohort and demonstrated data export to Phenopackets and FHIR. RareLink can enhance the clinical utility of REDCap through its global applicability, supporting equitable rare disease research. Broader adoption and coordination with international entities are thus essential to realise its full potential.

Abstract

Grants and funding