Solvathons Boost Rare Disease Diagnosis Efforts

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 multi-omics profiling, has improved diagnostic yield, but also introduced analytical complexity. 

Tackling this complexity requires systematic multidisciplinary collaboration. One promising approach is performing targeted diagnostic workshops that bring clinicians, scientists, and bioinformaticians together to reanalyse unresolved cases.

The Solvathon model

Solve-RD consortium,  a pan-European initiative funded by the European Commission from 2018 to 2024, developed a novel workshop format called Salvathon. Designed to improve diagnostic yield, these structured events combined multi-omics reanalysis with expert input and hands-on case work. Over 100 partners across 26 countries contributed to the effort. As described in a new Perspective article in Nature Genetics, four Solvathons conducted under Solve-RD directly contributed to more than 100 new diagnoses for patients with previously unsolved rare diseases.

Participants brought real, unsolved patient cases to the table, enabling focused high-impact collaboration. Using fast-evolving technologies, data analysis and interpretation methodologies, and growing databases, Solvathons not only allowed diagnosis, but also became a hub for training, enabling uptake of new methodologies in diagnostic testing and research.

To ensure reproducibility and scalability, the Solve-RD team emphasised the importance of standardised frameworks for annotation and interpretation. Detailed protocols for data sharing, visualisation, and collaborative interpretation are essential to enable effective joint analysis and facilitate knowledge transfer between datasets and research teams.

GHGA tools in action

Two of the four Solvathons were co-organized by GHGA co-spokesperson Julien Gagneur and his team at the TU Munich, while GHGA co-spokesperson Holm Graessner oversaw all four events. Using GHGA workflows like DROP, the bioinformatics NGS results were promptly prepared and released in a secure IT infrastructure during the event.

Looking ahead

Building on the success of Solve-RD, the Solvathon model will continue under ERDERA, the new European Rare Disease Research Alliance. With over 180 partners and a seven-year Horizon Europe mandate, ERDERA will expand Solvathons across Europe. This will connect national undiagnosed disease programs, support training efforts, and strengthen cross-border diagnostics.

As rare disease genomics continues to grow in scale and complexity, Solvathons represent a practical and powerful way to bring experts together, advance diagnoses, and ensure that patients benefit from the latest innovations in biomedical research.