Category: News

Solve-RD paper on our interconnected data infrastructure is out!

Solve-RD paper on our interconnected data infrastructure is out!

Over the past five years, an ambitious collaboration has unfolded across 51 research institutes in 15 European countries. This effort, part of the Solve-RD project (HORIZON 2020 grant number 779257) and led by the University of Tübingen, aimed to unlock genetic diagnoses for patients with rare diseases who had reached the end of their diagnostic journey without answers.

At the heart of this project lies an extraordinary achievement: over 818 terabytes of data from more than 19,000 experiments were produced and reanalyzed, and securely stored at the EMBL-EBI European Genome-Phenome Archive (EGA). The data, contributed by six European Reference Networks, were combined with thousands of additional novel omics datasets, all processed and analyzed using cutting-edge and customized methods.

The backbone of this ambitious project was an interconnected data infrastructure that bridged existing components seamlessly. Participating centers submitted their data to the RD-Connect Genome-Phenome Analysis Platform (GPAP), hosted by the Centro Nacional de Análisis Genómico (CNAG) in Barcelona, where the data could also undergo advanced analysis. A high-performance computing cluster, or Sandbox, at the University Medical Center Groningen (UMCG) provided a testing ground for data analysts to explore and apply novel, best-in-class tools.

To ensure comprehensive tracking and discovery, cases were managed using the MOLGENIS RD3 database and Café Variome Discovery Nexus, developed by the UMCG and the University of Leicester, respectively. The integration of Beacon technology and a connection to Matchmaker Exchange further enhanced the discoverability of Solve-RD datasets, facilitating crucial patient matchmaking.

The innovative infrastructure and findings from this project are detailed in a recent paper published in GigaScience (https://doi.org/10.1093/gigascience/giae058) , showcasing the power of collaboration in pushing the boundaries of rare disease research:

Lennart F. Johansson, Steve Laurie, Dylan Spalding, [...] Sergi Beltran, Morris A. Swertz, Anthony J. Brookes, and Solve-RD consortium. An interconnected data infrastructure to support large-scale rare disease research. Gigascience. 2024 Jan 2:13:giae058. doi: 10.1093/gigascience/giae058.

Solve-RD industry workshop: Strategies for omics data analysis & reanalysis – recording available

Solve-RD industry workshop: Strategies for omics data analysis & reanalysis - recording available

On Thursday, 20 June 2024, Solve-RD organized a webinar “Solve-RD industry workshop: Strategies for omics data analysis & reanalysis”. The aim was to present participants from industry the strategies we developed for Solve-RD for omics data analysis and reanalysis, and to discuss challenges, advantages as well as future developments.

The recording has been uploaded to our Solve-RD YouTube channel and is available via this link.

New Publication: Model matchmaking via the Solve-RD Rare Disease Models & Mechanisms Network (RDMM-Europe)

New Publication: Model matchmaking via the Solve-RD Rare Disease Models & Mechanisms Network (RDMM-Europe)

The European Rare Disease Models & Mechanisms Network (RDMM-Europe) has been established within Solve-RD. RDMM-Europe is a brokerage service to promote fruitful collaborations between clinicians and model organism experts with the aim of filling the gap between RD gene discovery and functional validation of potentially new disease genes and/or novel disease mechanisms.

In our article we describe the network and infrastructure that we have successfully implemented to support the use of model organisms in rare disease research, we share our processes and highlight several examples of modeling approaches that clearly illustrate the benefit and need of functional validation in model organisms to accelerate the assessment of new disease-gene associations. The article also showcases the main objectives of the funded projects, highlights examples of validation projects in different models and provides links to recent publications related to some of these projects.

The article has now been accepted for publication in Lab Animal: Kornelia Ellwanger, Julie A. Brill [...] Olaf Riess. Model matchmaking via the Solve-RD Rare Disease Models & Mechanisms Network (RDMM-Europe). Lab Anim (NY). 2024 Jun 24. https://doi.org/10.1038/s41684-024-01395-2. Epub ahead of print.

Solve-RD industry workshop

Solve-RD industry workshop: Strategies for omics data analysis & reanalysis

Date: Thursday, 20 June 2024, 12:00-13:30 CEST | online

Aim: The strategies we developed for Solve-RD for omics data analysis and reanalysis will be presented. We will discuss challenges, advantages as well as future developments.

Participants: Representatives from industry

Agenda:

  1. Welcome
  2. Data reanalysis approach - Sergi Beltran (CNAG, Barcelona, Spain)
  3. Solvathon concept - Holm Graessner (Uni Tübingen, Germany)

    • Example from RNAseq & multi-omics Solvathon - Vicente Yepez (TU Munich, Germany) & Anna Esteve (CNAG, Barcelona, Spain)
    • Example from long-read sequencing &  Optical Genome Mapping Solvathon - Alexander Hoischen (RadboudUMC, Nijmegen, the Netherlands)
  4. Q & A
  5. Perspective - Holm Graessner (Uni Tübingen, Germany)

RDMM-Europe project published!

RDMM-Europe project published!

Solve-RD partner Laurence Faivre from CHU Dijon and colleagues from CHU Rouen, France identified 5 patients with a recurrent de novo variant p.(Arg126Gln) in FEM1B and a neurodevelopmental disorder associated with a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities.

The RDMM-Europe Seeding Grant awarded to Ype Elgersma at Erasmus University Medical Center in Rotterdam helped to assess the pathogenicity of this rare genetic variant. The project involved expression of the mutant form in developing mouse embryos and in primary neuronal cultures and demonstrated the toxicity of FEM1BR126Q variant compared to FEM1B.

The collaborative work was now accepted for publication in Genetics in Medicine:

François Lecoquierre, […] Laurence Faivre, Ype Elgersma, Antonio Vitobello. A recurrent missense variant in the E3 ubiquitin ligase substrate recognition subunit FEM1B causes a rare syndromic neurodevelopmental disorder. Genetics in Medicine, Volume 26, Issue 6, 2024, 101119, ISSN 1098-3600, https://doi.org/10.1016/j.gim.2024.101119

Solve-RD Solvathon on multi-omics analysis

Solve-RD Solvathon on multi-omics analysis

Solve-RD Solvathon on multi-omics analysis (with focus on RNAseq and Epigenetics data integration)

Wed-Fri, 6-8 March 2024 in Barcelona, Spain.

Goal: 3 days hands-on course to instruct ERNs how to analyse and interpret the different results derived from Epigenetics analysis and RNAseq, in combination with variants from DNA, with the aim of diagnosing cases.

Participants: Representatives from the Epigenetics and RNAseq working groups, representatives from ERNs/Solve-RD partners who contributed samples and are involved in the analysis/interpretation.

Proposed agenda:

Wednesday, 6 March 2024
9-13 theory session
13-17 hands on work and interpretation

Thursday, 7 March 2024
9-11 theory / findings and questions from day 1
11-17 hands on work and interpretation

Friday, 8 March 2024
9-11 hands on / preparation of presentations on interesting findings and solved cases
11-13 solved cases presentation and wrap up
13 end /departure

Registration link: https://docs.google.com/forms/d/e/1FAIpQLSeYH6avlkgTmbNLcgUtwMBVU7HehWWDMX1FG-rfOX-bYgv8gA/viewform?usp=sf_link

Deadline for registration: 10 January 2024.

Please note: on-site participants will be selected based on the number of submitted samples and data to analyse. You will hear back from us by 15 January 2024.

We plan to enable online participation for the theory sessions and will share the presentations and recordings to provide resources and guidance for Solve-RD partners that cannot attend live.

Solve-RD Solvathon on LR-WGS and optical genome mapping (OGM) analysis

Solve-RD Solvathon on LR-WGS and optical genome mapping (OGM) analysis

Mon-Wed, 19-21 February 2024 in Nijmegen, the Netherlands.

Goal: 3 days hands-on course to instruct ERNs how to analyse and interpret the different results derived from LR-WGS and optical genome mapping (OGM), with the aim of diagnosing cases.

Participants: Representatives from the LR-WGS and OGM working groups, representatives from ERNs/Solve-RD partners who contributed samples and are involved in the analysis/interpretation.

Proposed agenda:

Monday, 19 Feb 2024
9-11 theory session (LRS)
11-17 hands on work and interpretation (LRS)

Tuesday, 20 Feb 2024
9-11 theory session (OGM)
11-17 hands on work and interpretation (OGM+LRS)

Wednesday, 21 Feb 2024
9-11 hands on work and interpretation (OGM+LRS)
11-12:30 solved cases presentation and closing remarks
12:30 end /departure

Registration link: https://docs.google.com/forms/d/e/1FAIpQLSdWe7VwUbBOltf1Ej2st505C8Wq3Jinjc8uxodlWrGj2Qnj8Q/viewform?usp=sf_link

Deadline for registration: 10 January 2024.

Please note: on-site participants will be selected based on the number of submitted samples and data to analyse. You will hear back from us by 15 January 2024.

We plan to enable online participation for the theory sessions and will share the presentations and recordings to provide resources and guidance for Solve-RD partners that cannot attend live.

RDMM-Europe project published!

RDMM-Europe project published!

Solve-RD partners and Henry Houlden at the UCL Queen Square Institute of Neurology identified novel missense variants in the gene ACBD6 in a large cohort of unrelated patients with complex dystonia parkinsonism ataxia phenotype. The patients presented moderate-to-severe delay in psychomotor development predominantly affecting the acquisition of walking skills, speech, intellectual functioning (global developmental delay, moderate to severe intellectual disability, severe speech disorder, diverse behavioural abnormalities), variable dysmorphisms and seizures. The RDMM-Europe committees suggested to connect the group with Gaurav K. Varshney at the Oklahoma Medical Research Foundation and Solve-RD provided Seeding Grant funding to support the validation of the gen disease association using zebrafish as a model.

The collaborative work was now accepted for publication in Brain.

Rauan Kaiyrzhanov, Aboulfazl Rad, Sheng-Jia Lin [...] Reza Maroofian. Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders. Brain (2023) https://doi.org/10.1093/brain/awad380

Solvathon

Solvathon

Solve-RD is organizing three “Solvathons” - data analysis and interpretation workshops on different topics in the remaining time of the project.

See below the information on the different workshops and please save the dates and register if you are interested to participate.

 

Solvathon on SR-WGS analysis (online): 6-8 November 2023

Goal: Instruct Solve-RD partners of all ERNs on how to analyze and interpret the results derived from WGS experiments by the DATF working groups with the aim of diagnosing cases.

Analysis cohort:  1,885 novel SR-WGS experiments representing 866 RD families and 1,590 WGS experiments (submitted for re-analysis) representing 764 families.

Audience: All Solve-RD partners that have contributed WGS data or samples for SR-WGS.

Further details (agenda, exact timetable, calendar invite and connection info) will be shared in due time. We plan to have sessions covering only half days in the above timeframe and people are not expected to attend all sessions.

Please get registered and save the date in your calendar!

 

Solvathon on LR-WGS and OGM analysis (in Nijmegen, the Netherlands): 19-21 February 2024

 Goal: Instruct Solve-RD partners of all ERNs on how to analyze and interpret the results derived from LR-WGS and Optical Genome Mapping (OGM) with the aim of diagnosing cases.

Analysis cohort:  All Solve-RD LR-WGS experiments and OGM experiments analyzed by the above mentioned date.

Audience: All Solve-RD partners that have contributed samples for LR-WGS and/or OGM. The number of on-site participants is limited and we might have to select participants based on the number of experiments for interpretation. We will facilitate online participation that is open for all interested Solve-RD participants at least for the theoretical part.

Further details (agenda, timelines and pre-registration form) will be shared in due time.  Please save the date in your calendar!

 

Solvathon on multi-omics (in Barcelona, Spain): 6-8 March 2024

Goal: Instruct Solve-RD partners of all ERNs on how to integrate and interpret results derived from multi-omics experiments with the aim of diagnosing cases.

Analysis cohort:  All Solve-RD cases with multi-omics experiments.

Audience: All Solve-RD partners that have submitted patients samples analysed by different combined -omics technologies. The number of on-site participants is limited and we might have to select participants based on the number of experiments for interpretation. We will facilitate online participation that is open for all interested Solve-RD participants at least for the theoretical part.

Further details (agenda, timelines, pre-registration form) will be shared in due time. Please save the date in your calendar!

Time to Act – Improving rare disease diagnosis and solving the unsolved rare disease through collaboration in europe

 

 

TIME TO ACT – IMPROVING RARE DISEASE DIAGNOSIS AND SOLVING THE UNSOLVED RARE DISEASE THROUGH COLLABORATION IN EUROPE

The Solve-RD consortium and associated European Solve-RD network, including among others six European Reference Networks, EURORDIS, Orphanet and leading European Rare Disease Clinicians and Researchers in 20 countries, call upon all European RD stakeholders, including EU Member States, the European Commission, the Council of the European Union, the general public and private organisations active in the RD field, as well as the rare disease community at large to act NOW to seize the current once-in-a-generation opportunity to significantly improve rare disease diagnosis in Europe.

This unique opportunity is characterized by pan-European access to diagnostic technologies in particular Whole Exome Sequencing, the just reached maturity of the European Refence Networks ecosystem, the looming opportunity to share rare disease data on European-wide scale within the forthcoming European Health Data Space, the upcoming RD-Partnership as well as - with Solve-RD - the availability of a scalable transnational diagnostics research platform.

Solve-RD has summarized the critical action points in this Policy Paper.

We call upon all European rare disease stakeholders to partner to jointly improve rare disease diagnosis!