Periodic report RP3

Periodic report RP3

The Solve-RD periodic report for the third reporting period has just been submitted.

In the last 18 months (from 01/2021 to 06/2022), we continued to implement the activities addressing the three challenges (see here).

We reached our goal and collected 21,348 datasets (phenotypic & exome/genome sequencing data) from unsolved RD patients and their family members. Standardised phenotypic information (HPO, ORDO & OMIM encoded) has been collected via the RD-Connect GPAP PhenoStore module.

We have continued producing and enriching the Rare Disease Case Ontology (RDCO). Up to now, RDCO has been populated with 412,500 similarity associations.

Re-analysis of data freezes 1 & 2 has been done by the Data Analysis Task Force DATF working groups. Results have been prioritized and interpreted by the Data Interpretation Task Forces (DITFs) of each ERN. This collaborative effort led to the diagnosis of 511 patients from 6,003 families. This is already an 8.5 % additional diagnostic rate although many of the analyses and evaluations are still ongoing. The new re-analysis approach pursued in Solve-RD as well as the structures we established to warrant best exchange of expertise have been published in a series of papers in the EJHG in June 2021.

Service providers have been chosen for all novel omics technologies. SOPs for biomaterials have been shared with all ERN partners via the DITFs. Sample shipment is only slowly progressing; however, >3,000 samples have been sent to the central lab in Nijmegen for QC and then further distributed to the respective service providers.

The RDMM-Europe brokerage service connecting Solve-RD partners who discovered novel RD genes with model organism scientists that have the expertise to functionally validate these genes and variants opened 10 calls for Connection Applications. 36 Seeding Grants have been awarded so far.

The co-designed models for the communication of genomic results for RD have been published (Costa et al.). The main finding at both study sites in the Czech Republic and the UK was the identification of post-test care as the shared priority for improvement for both health professionals and families.

The conference ECOgenomics “European Conference on the Diffusion of Genomic Medicine: Health Economics & Policy” took place online from 26-28 May 2021. Plenary sessions and parallel thematic sessions brought together researchers from the human sciences (mainly health economics), but also researchers from other disciplines.

The Treatabolome database has been released and an API connects it to the RD-Connect GPAP to make information about treatable genes and variants of RDs accessible and to improve the visibility of existing variant-specific treatment options at the time of diagnosis to clinicians and their patients. It includes data from 10 systematic literature reviews of which six have been published in a special issue in May 2021 in the JND.

The data flow system has continuously been adapted to the project’s needs involving GPAP, the EGA, omics service providers, the sandbox and RD3. GPAP’s new Cohort App module facilitates the exploration and construction of cohorts on experiments metadata and structured clinical data using standard ontologies to improve the analysis of defined cohorts. The FUSE client enables access to files stored at the EGA via the Sandbox and also for real-time visualisation in a genome browser like IGV when analysing data in the GPAP.

MSCA Action

MSCA-PF 2022 in peripheral nerve and muscle disease at University of Antwerp, Belgium

The Peripheral Neuropathy and Translational Neurosciences groups of the µNEURO Research Centre of Excellence (University of Antwerp, Belgium) welcome expressions of interest from postdoctoral researchers with a strong scientific track record to jointly prepare a high-quality proposal for an MSCA Postdoctoral Fellowship 2022 in the field of neuromuscular disease and peripheral nerve degeneration.

More info can be found here.

Solve-RD Annual Meeting 2022

Solve-RD Annual Meeting 2022

The Solve-RD Annual Meeting took place from Monday to Tuesday, 25-26 April 2022. Although virtually, it was a success!
It was great to see the results coming out of the project and to listen to all the fantastic presentations – especially from so many junior scientists. Congratulations to Robin Wijngaard (Nijmegen) and Vicente Yépez (Munich) for the best full presentation as well as Elke de Boer (Nijmegen) for the best flash talk!

Racing against time: Seeking the cure for a deadly disease

Racing against time: Seeking the cure for a deadly disease

Ten years ago, Harvard Law School student Sonia Vallabh’s world was turned upside down when her mother’s health rapidly deteriorated after initial complaints of trouble with her vision. Descending quickly into dementia, pneumonia, and disability, it was not until after the death of Sonia’s mother that a diagnosis for prion disease was confirmed. But the nightmare did not stop there — Sonia soon found out that she, too, had inherited the deadly disease.

We are very grateful that Sonia Vallabh and Eric Minikel accepted the invitation to give the keynote lecture at our Solve-RD Annual Meeting 2022! It was impressive to hear their story and to feel their determination to find a treatment for Sonia’s disease.

Prior to the meeting we have invited Sonia to share her thoughts on the future of rare disease research, as well as her own race against time to come up with a life-saving treatment. Read the full interview here.

We would like to inform you  that Sonia and Eric helped to launch a prion disease registry at This is a tool to help recruit for clinical research and also someday, clinical trials. In the meantime, numbers from the registry help to convince partners across sectors that even though this is a rare disease, they are well organised and capable of running rigorous clinical trials. So, by signing up, patients and families help to convince the world that this disease is worth working on!

Open position: Research Associate in Neurobiology/Mitochondrial Biology

Job opportunity: Research Associate in Neurobiology/Mitochondrial Biology

Solve-RD associated partner Rita Horvath lab at the University of Cambridge, UK is lookig for a Research Associate in Neurobiology/Mitochondrial Biology (Fixed Term) to identify how mitochondrial function is affected and which substrates and pathways are commonly and differently impaired in selected cell types of patients with mitochondrial diseases.

More info can be found here. Application deadline is 10 May 2022!

Solve-RD workshop: Navigating the Sandbox

Solve-RD workshop: Navigating the Sandbox

Solve-RD WP4 is organising a workshop on how to navigate the Sandbox.

Date & Time: Thursday, 19 May 2022, 14:00 - 15:30 CEST

Registration link:



This combined webinar & workshop will provide an update on Solve-RD Sandbox services/functions, and also consider future plans, needs and possibilities. Intended participants include ERN data controllers/producers (to ensure that their data is being managed in ways they are happy with) and DITF members (to ensure they have services they need now and going forward).

To begin, the current status of the Sandbox will be presented, including its RD3 metadata layer and the Discovery-Nexus support capabilities. Via these components, users can find, filter, and access cases and related data and results. The system will be demonstrated for some example use cases. The meeting will then transition into a workshop activity, to gather reflections from participants, and propose improvements for the future. This will encompass possibilities within and beyond Solve-RD, including multi-omic data analyses and the ambition of federating services with those of EJP-RD and GPAP.



  1. Overview (Presenter: Joeri van der Velde, UMC Groningen & Anthony Brookes, University of Leicester)  | 40 minutes
    - Sandbox design and utility
    - RD3 metadata database
    - Discovery-Nexus capabilities
  2. Demo: Finding cases/data and creating cohorts (Presenter: Colin Veal, University of Leicester & Joeri van der Velde, UMC Groningen) | 20 minutes
  3. Discussion (Chair: Morris Swertz, UMC Groningen) | 30 minutes
    - Bidirectional Q+A regarding unmet needs and system improvements
    - Proposal for federation with GPAP, EJP-VP, 1+MG, Beacon, etc.

Annual Meeting 2022: registration now open!

Solve-RD Annual Meeting 2022: registration now open!

The Solve-RD Annual Meeting 2022 will take place on Monday and Tuesday, 25 & 26 April. Due to the current situation it will again be fully online.

All Solve-RD beneficiaries, associated partners and collaborators are invited to register for the meeting. The registration is open until 18 April via this link.

Further information can be found here.

Solve-RD GPAP webinars 2021 on YouTube

Solve-RD GPAP webinars on YouTube

Solve-RD uses the RD-Connect Genome-Phenome Analysis Platform (GPAP) to analyse exome and genome sequencing data of rare disease patients. In October 2021 we organised two webinars: one on basic analysis using GPAP and the other on advanced platform features. Both webinars are now online:

Solve RD webinar on basic analysis using the RD-Connect Genome-Phenome Analysis Platform (GPAP) given by Steven Laurie (CNAG-CRG) on 6 Oct 2021

Solve RD webinar on advanced features of the RD-Connect Genome-Phenome Analysis Platform (GPAP) given by Leslie Matalonga (CNAG-CRG) on 19 Oct 2021

Solve-RD at the IMPC 2021 conference

Solve-RD at the IMPC 2021 conference

The ‘Mouse Genetics and Genomic Medicine’ virtual conference organised from 23-24 September 2021 by the International Mouse Phenotyping Consortium –IMPC ( will celebrate the occasion of the 10th anniversary of the establishment of the IMPC.

Solve-RD will present a poster on "Model Matchmaking via the Rare Diseases Models & Mechanisms Network (RDMM-Europe)".

In medical genetics, there is a critical need for model organism research, to assess new disease-gene associations, to understand pathophysiology and to test potential therapies. Within the Solve-RD project we established the European Rare Disease Models & Mechanisms Network (RDMM-Europe) to facilitate fruitful collaborations of model organism researchers and clinicians following patients with rare diseases (RD). The principle of this brokerage service is to fill the gap between RD gene discovery and functional validation. For that purpose, we connect Solve-RD clinicians that have discovered new disease-causing genes with model organism investigators (MOIs) that can study the mechanistic role of the given genes in health and disease by using an appropriate model organism or cell culture system. Solve-RD supports these validation projects with 50 Seeding Grants of 20,000 EUR each.

For the selection of candidate genes and model matchmaking, a two-committee process and a registry were set up using the structures of the successful Canadian RDMM Network as role model. The RDMM-Europe registry is a database that allows all interested MOIs to register the genes and model organisms they work with. Registrants express interest in getting linked to clinicians representing patients with RD and collaborating in projects funded by Solve-RD. The RDMM-Europe registry is also linked to international partner networks. Connection Applications on novel RD candidate genes are submitted by Solve-RD clinicians and are evaluated and approved by the Clinical Advisory Committee. Upon approval, the project management office opens a call for tender to identify best matching MOIs for the requested validation work and invites them to submit Seeding Grant Applications. They are evaluated by a Scientific Advisory Committee and approved for funding.

To date, we have awarded 23 Seeding Grants to MOIs and have linked Solve-RD scientists to model researchers in eight European countries, Canada, USA, Qatar and Australia. Linking scientists across borders via the RDMM network and supporting these joint projects will advance RD research and will benefit patients and families living with RD.

View the poster here.

EJP RD Fellowship experience in Bonn, Germany

EJP RD Fellowship experience in Bonn, Germany

Núria Dueñas, a medical oncologist and PhD candidate at the Catalan Institute of Oncology (ICO/IDIBELL) in Barcelona, spent 6 weeks at the Institute of Human Genetics of the University Hospital Bonn, Germany to conduct research with Solve-RD partner Stefan Aretz. They investigated whether different hereditary colorectal cancer risks can be in part attributable to the accumulation of low-risk SNPs in patients with Lynch syndrome. Her stay was supported by the EJP RD fellowship program.

Núria Dueñas is a medical oncologist with a special interest in cancer genetics and hereditary cancer. Since 2018, she works as a physician in the Hereditary Cancer Program of the Catalan Institute of Oncology (ICO/IDIBELL) in Barcelona and as a PhD student co-supervised by Marta Pineda and Joan Brunet. In the past years, she focussed on hereditary colorectal cancer (CRC) and Lynch syndrome (LS). Her PhD project is on risk estimation and phenotype-genotype correlation in LS.

Núria Dueñas

In LS, as in other hereditary cancer predisposition syndromes characterized by incomplete penetrance, one of the main challenges is to identify which risk-modifying factors may be modulating the expression of the oncological disease. Common low-risk alleles (SNPs) for CRC can be integrated in Polygenic Risk Scores (PRS) which have been shown to model CRC risk in the general population as one type of genetic risk modifiers, but to date their effect on CRC risk in LS individuals is still largely unknown.

Núria spent 6 weeks at the Institute of Human Genetics of the University Hospital Bonn, Germany in the group of Stefan Aretz. They investigated whether different CRC risks can be in part attributable to the accumulation of low-risk SNPs in LS individuals. In particular, Núria gathered and aggregated clinical data of the LS cohort in Bonn (n=500) and supported the biostatistics team in Bonn to apply the Barcelona PRS pipeline. This collaborative project continues now that she is back in Barcelona through the application of additional models to calculate the PRS. Also, a meta-analysis combining the two populations included (Bonn and Barcelona) will be conducted. The collaborative study will hopefully lead to a first publication of the findings; follow-up projects are already planned.

The EJP-RD mobility fellowship has been a unique opportunity for Núria. She said: “Collaborating with professionals from different specialties and different countries has helped, not only to generate new knowledge in translational research and in the development of research projects but also to learn different ways of approaching scientific research”. Moreover, she has had the chance to refresh her German speaking skills – at least to order food and drinks by herself. And she was able to enjoy the rainiest summer of her life!