Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases

Abstract

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient’s data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe.

The RD‐Connect Genome‐Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases

“…Before the initiation of the Solve‐RD project, the three largest projects which had used the system for primary analysis were NeurOmics (https://cordis.europa.eu/project/id/305121/reporting, n = 1,117 data sets), the Biobanking and Biomolecular Research Infrastructure—Large Prospective Cohorts (BBMRI‐LPC, https://cordis.europa.eu/project/id/313010/reporting) exome sequencing project ( n = 757), and the Consequitur project ( n = 626, Kurul et al, 2021). Currently, the Solve‐RD project is using the RD‐Connect GPAP as a key resource for the collection and reanalysis of 19,000 previously unsolved genome‐phenome datasets (Zurek et al, 2021). In addition, the RD‐Connect GPAP is further developed and made available to all European researchers through the EJP‐RD Virtual Platform, and also as an ELIXIR‐ES resource.…”

“…As a result, phenotypic and genomics data can be re-used within the RD-Connect GPAP or beyond if it is shared within a consortium infrastructure, and/or submitted to a resource enabling controlled access such as the EGA. The Solve-RD project provides a good demonstration of how data can be successfully shared and used within a consortium to undertake further analyses beyond those which are currently possible within the RD-Connect GPAP (Zurek et al, 2021).…”

FAIR Genomes metadata schema promoting Next Generation Sequencing data reuse in Dutch healthcare and research

“…It contains rich metadata on NGS subjects, samples, lab processes and files from the SolveRD project 61 , which performs re-analysis of >19,000 unsolved rare disease patients. Data freeze 1 of SolveRD includes data from 8,393 individuals 62 . The data structure had been kept compatible with FAIR Genomes for elements concerning phenotypes, absent phenotypes, recontact details, family and sex information, tissue and material types, anatomical locations, file types and locations, enrichment kits, type of sequencing, studies, and so on.…”

Intellectual disability genomics: current state, pitfalls and future challenges

“…Nevertheless, assembly patients that comply to these characteristics is problematic, particularly in rare ID syndromes. To overcome this bottleneck several open-access online platforms allow data sharing: GeneMatcher ( https://genematcher.org ) [ 132 , 133 ], Human Disease Genes website series ( http://humandiseasegenes.info ) [ 134 ], PhenomeCentral ( https://www.phenomecentral.org ) [ 135 ], Leiden Open Variation Database (LOVD, https://www.lovd.nl ) [ 136 ], Clinvar ( https://www.ncbi.nlm.nih.gov/clinvar ) [ 117 ], and Solve-RD - solving the unsolved rare diseases ( https://solve-rd.eu ) [ 137 ], among others. …”