The Solve-RD Solvathons as a pan-European interdisciplinary collaboration to diagnose patients with rare disease

Vicente A Yépez¹, German Demidov², Kornelia Ellwanger², Steven Laurie^{3

4}, Rebeka Luknárová¹, Midhuna Immaculate Joseph Maran⁵, Thomas Hentrich⁵, Lydia Sagath⁶, Bart van der Sanden⁶, Galuh Astuti⁶, Kornelia Neveling⁶, Laura Batlle-Masó^{7

8}, Danique Beijer⁹, Felix Brechtmann¹, Andrés Caballero-Oteyza^{10

11}, Marc Dabad^{3

4}, Anne-Sophie Denommé-Pichon^{12

13}, Cenna Doornbos^{14

15}, Zakaria Eddafir^{16

17}, Berta Estévez-Arias^{18

19}, Ozge Aksel Kilicarslan²⁰, Ingrid H M Kolen²¹, Leon Kraß^{1

22

23}, Katja Lohmann²⁴, Shubhankar Londhe^{1

23

25}, Estrella López-Martín²⁶, Kars Maassen²⁷, William Macken²⁸, Beatriz Martínez-Delgado^{26

29}, Davide Mei³⁰, Christian Mertes^{1

22}, Raffaella Minardi³¹, Heba Morsy^{28

32}, Juliane S Mueller³³, Daniel Natera-de Benito^{18

34

35}, Isabelle Nelson³⁶, Machteld M Oud⁶, Ida Paramonov^{3

4}, Daniel Picó^{3

4}, Davide Piscia^{3

4}, Kiran Polavarapu²⁰, Emanuele Raineri³, Marco Savarese³⁷, Noor Smal³⁸, Marloes Steehouwer⁶, Wouter Steyaert^{6

14}, Morris A Swertz³⁹, Mirja Thomsen²⁴, Ana Töpf⁴⁰, Liedewei Van de Vondel^{41

42

43}, Gerben van der Vries³⁹, Antonio Vitobello^{12

13}, Carlo Wilke^{44

45}, Birte Zurek²; Solve-RD DITF-EPICARE; Solve-RD DITF-ITHACA; Solve-RD DITF-EURO-NMD; Solve-RD DITF-RITA; Solve-RD DITF-RND; Solve-RD consortium; Peter-Bram T' Hoen^{14

15}, Leslie Matalonga^{3

4}, Lisenka E L M Vissers^{6

46}, Christian Gilissen^{6

14}, Julia Schulze-Hentrich⁵, Sergi Beltran^{3

47}, Anna Esteve-Codina^{3

4}, Alexander Hoischen^{6

48}, Julien Gagneur^{49

50

51}, Holm Graessner^{52

53}

Affiliations

¹ School of Computation, Information and Technology, Technical University of Munich, Garching, Germany.
² Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
³ Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
⁴ Universitat de Barcelona, Barcelona, Spain.
⁵ Department of Genetics/Epigenetics, Faculty NT, Saarland University, Saarbrücken, Germany.
⁶ Department of Human Genetics, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, the Netherlands.
⁷ Infection in Immunocompromised Pediatric Patients Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
⁸ Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d'Hebron University Hospital, Barcelona, Spain.
⁹ Division Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.
¹⁰ RESIST-Cluster of Excellence 2155 to Hannover Medical School, Satellite Center Freiburg, Freiburg, Germany.
¹¹ Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert Ludwigs University of Freiburg, Freiburg, Germany.
¹² Medical Genomics, FHU TRANSLAD, Dijon University Hospital, Dijon, France.
¹³ Unit 1231 GAD Team, Inserm, Burgundy Europe University, Dijon, France.
¹⁴ Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
¹⁵ Center for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, the Netherlands.
¹⁶ Applied and Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
¹⁷ Applied Translational Neurogenomics Group, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
¹⁸ Neuromuscular Disorders Unit, Department of Pediatric Neurology, Hospital Sant Joan de Déu, Barcelona, Spain.
¹⁹ Laboratory of Neurogenetics and Molecular Medicine, Center for Genomic Sciences in Medicine, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
²⁰ Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
²¹ Division of Neurodegenerative Diseases and Movement Disorders, Department of Neurology, Faculty of Medicine, Heidelberg University Hospital, Heidelberg, Germany.
²² Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany.
²³ Computational Health Center, Helmholtz Center Munich, Neuherberg, Germany.
²⁴ Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
²⁵ Helmholtz Association, Munich School for Data Science, Munich, Germany.
²⁶ Institute of Rare Diseases Research, Spanish Undiagnosed Rare Diseases Cases Program (SpainUDP), Undiagnosed Diseases Network International, Instituto de Salud Carlos III, Madrid, Spain.
²⁷ Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
²⁸ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
²⁹ CIBER of Rare Diseases (CIBERER), Madrid, Spain.
³⁰ Department of Neuroscience and Medical Genetics, Meyer Children's Hospital IRCCS, Florence, Italy.
³¹ IRCCS Istituto delle Scienze Neurologiche di Bologna, European Reference Network for Rare and Complex Epilepsies (EpiCARE), Bologna, Italy.
³² Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
³³ Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, London, UK.
³⁴ Applied Research in Neuromuscular Diseases, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
³⁵ Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
³⁶ Centre de Recherche en Myologie, Institut de Myologie, Inserm, Sorbonne Université, Paris, France.
³⁷ Folkhälsan Research Centre and Medicum, University of Helsinki, Helsinki, Finland.
³⁸ VIB-CMN, Applied and Translational Neurogenomics Group, University of Antwerp, Antwerp, Belgium.
³⁹ Department of Genetics, Genomics Coordination Center, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁴⁰ John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
⁴¹ Peripheral Neuropathy Research Group, University of Antwerp, Antwerp, Belgium.
⁴² Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
⁴³ Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
⁴⁴ Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
⁴⁵ German Center for Neurodegenerative Diseases, Tübingen, Germany.
⁴⁶ Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴⁷ Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
⁴⁸ Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴⁹ School of Computation, Information and Technology, Technical University of Munich, Garching, Germany. gagneur@in.tum.de.
⁵⁰ Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany. gagneur@in.tum.de.
⁵¹ Computational Health Center, Helmholtz Center Munich, Neuherberg, Germany. gagneur@in.tum.de.
⁵² Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany. holm.graessner@med.uni-tuebingen.de.
⁵³ Centre for Rare Diseases, University of Tübingen, Tübingen, Germany. holm.graessner@med.uni-tuebingen.de.

PMID: 40926087
DOI: 10.1038/s41588-025-02290-3

Review

The Solve-RD Solvathons as a pan-European interdisciplinary collaboration to diagnose patients with rare disease

Vicente A Yépez et al. Nat Genet. 2025 Oct.

. 2025 Oct;57(10):2361-2370.

doi: 10.1038/s41588-025-02290-3. Epub 2025 Sep 9.

Authors

Affiliations

¹ School of Computation, Information and Technology, Technical University of Munich, Garching, Germany.
² Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
³ Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
⁴ Universitat de Barcelona, Barcelona, Spain.
⁵ Department of Genetics/Epigenetics, Faculty NT, Saarland University, Saarbrücken, Germany.
⁶ Department of Human Genetics, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, the Netherlands.
⁷ Infection in Immunocompromised Pediatric Patients Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
⁸ Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d'Hebron University Hospital, Barcelona, Spain.
⁹ Division Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.
¹⁰ RESIST-Cluster of Excellence 2155 to Hannover Medical School, Satellite Center Freiburg, Freiburg, Germany.
¹¹ Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert Ludwigs University of Freiburg, Freiburg, Germany.
¹² Medical Genomics, FHU TRANSLAD, Dijon University Hospital, Dijon, France.
¹³ Unit 1231 GAD Team, Inserm, Burgundy Europe University, Dijon, France.
¹⁴ Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
¹⁵ Center for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, the Netherlands.
¹⁶ Applied and Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
¹⁷ Applied Translational Neurogenomics Group, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
¹⁸ Neuromuscular Disorders Unit, Department of Pediatric Neurology, Hospital Sant Joan de Déu, Barcelona, Spain.
¹⁹ Laboratory of Neurogenetics and Molecular Medicine, Center for Genomic Sciences in Medicine, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
²⁰ Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
²¹ Division of Neurodegenerative Diseases and Movement Disorders, Department of Neurology, Faculty of Medicine, Heidelberg University Hospital, Heidelberg, Germany.
²² Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany.
²³ Computational Health Center, Helmholtz Center Munich, Neuherberg, Germany.
²⁴ Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
²⁵ Helmholtz Association, Munich School for Data Science, Munich, Germany.
²⁶ Institute of Rare Diseases Research, Spanish Undiagnosed Rare Diseases Cases Program (SpainUDP), Undiagnosed Diseases Network International, Instituto de Salud Carlos III, Madrid, Spain.
²⁷ Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
²⁸ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
²⁹ CIBER of Rare Diseases (CIBERER), Madrid, Spain.
³⁰ Department of Neuroscience and Medical Genetics, Meyer Children's Hospital IRCCS, Florence, Italy.
³¹ IRCCS Istituto delle Scienze Neurologiche di Bologna, European Reference Network for Rare and Complex Epilepsies (EpiCARE), Bologna, Italy.
³² Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
³³ Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, London, UK.
³⁴ Applied Research in Neuromuscular Diseases, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
³⁵ Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
³⁶ Centre de Recherche en Myologie, Institut de Myologie, Inserm, Sorbonne Université, Paris, France.
³⁷ Folkhälsan Research Centre and Medicum, University of Helsinki, Helsinki, Finland.
³⁸ VIB-CMN, Applied and Translational Neurogenomics Group, University of Antwerp, Antwerp, Belgium.
³⁹ Department of Genetics, Genomics Coordination Center, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁴⁰ John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
⁴¹ Peripheral Neuropathy Research Group, University of Antwerp, Antwerp, Belgium.
⁴² Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
⁴³ Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
⁴⁴ Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
⁴⁵ German Center for Neurodegenerative Diseases, Tübingen, Germany.
⁴⁶ Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴⁷ Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
⁴⁸ Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴⁹ School of Computation, Information and Technology, Technical University of Munich, Garching, Germany. gagneur@in.tum.de.
⁵⁰ Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany. gagneur@in.tum.de.
⁵¹ Computational Health Center, Helmholtz Center Munich, Neuherberg, Germany. gagneur@in.tum.de.
⁵² Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany. holm.graessner@med.uni-tuebingen.de.
⁵³ Centre for Rare Diseases, University of Tübingen, Tübingen, Germany. holm.graessner@med.uni-tuebingen.de.

PMID: 40926087
DOI: 10.1038/s41588-025-02290-3

Abstract

Despite advances in genomic diagnostics, the majority of individuals with rare diseases remain without a confirmed genetic diagnosis. The rapid emergence of advanced omics technologies, such as long-read genome sequencing, optical genome mapping and multiomic profiling, has improved diagnostic yield but also substantially increased analytical and interpretational complexity. Addressing this complexity requires systematic multidisciplinary collaboration, as recently demonstrated by targeted diagnostic workshops. Here, we highlight the experience of the Solve-RD consortium, a pan-European initiative, in implementing four structured workshops, termed 'Solvathons', as a regular and effective component of its operational workflow. We provide actionable insights, best practices and lessons learned for successful data integration, expert training and scalable collaborative diagnostics within large research consortia.

PubMed Disclaimer

Conflict of interest statement

Competing interests: V.A.Y. is founder, shareholder and managing director of OmicsDiscoveries. The other authors declare no competing interests.

References

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1. The 100,000 Genomes Project Pilot Investigators. 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report. N. Engl. J. Med. 385, 1868–1880 (2021). - DOI
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The Solve-RD Solvathons as a pan-European interdisciplinary collaboration to diagnose patients with rare disease

Affiliations

The Solve-RD Solvathons as a pan-European interdisciplinary collaboration to diagnose patients with rare disease

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous