UK OFFICE : +44 (0)1260 273 802
BRUSSELS OFFICE : +32 (0)2 895 5909

UK OFFICE : +44 (0)1260 273 802
BRUSSELS OFFICE : +32 (0)2 895 5909

Research for rare diseases
There are between 6,000 and 8,000 rare diseases; 75% of them affect children

Research for rare diseases


RD-Connect’s Libby Wood, Dorota Badowska, Lucia Monaco and Mary Wang highlight the important relationship between biobanks and rare diseases and consider what can be done to improve participation in collaborative research.

Funded by the European Union’s Seventh Framework Programme, RD-Connect is a unique infrastructure that brings together databases, patient registries, biobanks and clinical bioinformatics data to speed up research, improve diagnostic methods and accelerate the development of new therapeutics for the millions of people around the world affected by a rare disease.

To this end, the online resource, which is free for use by scientists and clinicians in Europe and across the globe, combines a Genome-Phenome Analysis Platform which links researchers with no bioinformatic training to clinical information about rare disease patients, a Registry&Biobank Finder, which directs researchers to patient registries and biobanks centred on their disease of interest, and a Sample Catalogue, which allows researchers to browse individual or collections of biosamples from rare disease patients.

Speaking to Pan European Networks Libby Wood, RD-Connect project manager, and Lucia Monaco and Mary Wang, two members of the biobanking work package, discuss some of the longstanding obstacles to data sharing and collaboration in the area of rare diseases and reflect on the particular role of biobanks in boosting research efforts.

Genome sequencing has transformed rare disease research – what is the importance of combining this genetic data with clinical expertise?

This is extremely important as 80% of rare diseases have a genetic component; the genomics revolution has brought hope of gene-based treatments for many rare diseases a step closer. We believe genomics and other newly emerging omics techniques hold the key to new diagnoses and therapies for rare diseases.

However, RD-Connect recognises that sequencing is only the first part of the story and does not replace clinical expertise – in fact, combining genetic and clinical data is more important than ever. The genome sequence of each individual has several hundred thousand ‘private’ variants that are not found in the general population. The majority of these changes are not directly disease causing, but may still be relevant for gene regulation and the symptom severity. Our current understanding of the underlying biology is often too limited for making appropriate predictions for an individual patient.

This is why all genomics data in the RD-Connect Genome-phenome Analysis Platform is linked to a detailed phenotypic description in PhenoTips. PhenoTips is a software tool that applies the human phenotype ontology (HPO). HPO ensures that all data collected is interoperable and computer readable. This is an important feature as though clinical expertise is essential, it is vital that clinical descriptions be standardised to increase the possibilities for sharing and comparison.

What is the especial importance of collaboration and interoperability in rare disease research, and what is to blame for continued data siloing?

Research in rare diseases is more challenging than in common diseases as there are fewer patients. This means less data is available and there are fewer experts to interpret it. Therefore, transnational and trans-disease efforts are essential to make optimal use of resources and ensure research is as effective and efficient as possible. Patient registries, biobanks and bioinformatics analysis tools are some of the key infrastructure tools required for research, which RD-Connect is supporting.  Hundreds of rare disease biobanks and patient registries already exist in Europe alone, and collaborative initiatives in specific disease groups (e.g. Huntington’s disease, cystic fibrosis and neuromuscular diseases) have advanced infrastructure harmonisation in several areas.

Despite the collaborative spirit seen in many rare disease fields there are still a number of bottlenecks and data are not routinely or systematically connected. The reasons for this data siloing are complex and some are longstanding – for example, the traditional lack of sharing in the academic community, which wants to protect results ahead of publication. There are additional obstacles with industry, which has greater concerns about intellectual property (IP) and confidentiality, in addition to asking more questions of data, and to ensure it is regulatory compliant. However, even when the will is there, issues such as lack of consent, poor infrastructure and lack of standards and interoperability can prevent sharing and lead to continued siloing.

However, there is great progress in the rare disease field, and RD-Connect is doing a lot of work to reduce the number of silos, in particular in the area of data interoperability and introducing standards for data collection, as well as providing tools to share genomics, phenotype and biosample information.

What role do biobanks play in the development of precision medicine for rare diseases?

As in the other areas discussed, the reduced numbers of patients with rare diseases mean it is also more challenging for researchers to get access to samples (DNA, RNA, tissue). Work on these samples is often key to a better understanding of disease mechanisms and for therapy development.

Biobanks are crucial in brokering access to larger numbers of samples to researchers who might not otherwise be able to access them. Biobanks provide reliable high-quality biological samples with associated clinical data, and have established, trusted infrastructures for the distribution of such samples. They are also in a position to manage the ethical issues relating to this type of work.

What are some of the key concerns rare disease patients and families have about biobanking and collaborative research involving data and biosample sharing, and how might these be addressed to ensure widespread participation?

Rare disease patients are often eager to participate in research, and biobanks can be an easy way to contribute. However, there are still concerns, including the privacy of data generated and the sample itself. One of the main concerns is that samples are actually useful to research and utilised to their full potential. The use of samples can be promoted through better visibility of biobanks and a more networked approach – something we are promoting through RD-Connect EuroBioBank. Patients also ask that results be fed back; this can be more challenging depending on contents in place.

If biobanks provided more information on the quality and ethical management of the samples, this would help patients to develop  trust and increase participation. It is important to have training and education to explain the importance of their contribution in allowing and validating rare disease research; this should be part of the informed consent process.

How is RD-Connect working to build the infrastructure necessary to achieve the IRDiRC objectives of delivering new therapies and diagnostics for rare diseases?

IRDiRC has recently updated its goals after reaching its target of 200 new therapies by 2020 earlier this year; the new goals still focus on accelerating diagnosis and access to therapies.

The most significant way RD-Connect is supporting these goals is through developing the resources and infrastructure needed to overcome the siloing, fragmentation and inaccessibility of datasets from different rare disease projects. RD-Connect has three main pillars of work, the Genome- Phenome Analysis Platform, the Registry&Biobank Finder, and the Sample Catalogue. These play different parts in facilitating diagnosis and therapy development.

The Genome-Phenome Analysis Platform is accelerating gene discovery and diagnosis by enabling researchers to analyse their own data and compare them with others to gain a complete view of their disease and patient population of interest. This has proven a success and, through many collaborations, RD-Connect has been involved in the identification of over a hundred novel rare disease genes and phenotypes.


1          For more information about the RD-Connect project, visit

2          To find out more about the biobank work taking place within RD-Connect, see


Libby Wood

Lucia Monaco

Mary Wang

Dorota Badowska

Communications and Impact Officer



This article will appear in issue three of Pan European Networks: Health, which will be published in November. 

Pan European Networks Ltd