December 2014  ●   Issue 10


Publication highlights

Current trends in biobanking for rare diseases: a review

Biospecimens held in biobanks are a valuable resource that allows researchers and clinicians to understand the mechanism and underlying cause of rare disease. Collections of DNA have been used to discover new genes and gene mutations, identify new diagnostic criteria, and genotype–phenotype correlations. On the other hand, sera and plasma have enabled the identification of new biomarkers and protein profiles to identify disease. Other types of biospecimens such as mRNA, cell lines, and tissues have assisted in collecting functional data to identify new pathways and new therapies to be applied to rare diseases. In the future, linking biobanks and registries with other data source will enable clinicians and researchers to gain a better understanding of a disease.

In a recent publication in the Journal of Biorepository Science for Applied Medicine (Current trends in biobanking for rare diseases: a review) RD-Connect, NeurOmics and EURenOmics partners review the current and future direction of rare disease biobanks and discuss the research and development stemming from the use of biospecimens and how this is used to improve management of rare diseases.

The full review and video abstract with commentary from RD-Connect partners Hugh Dawkins and Caroline Graham (Office of Population Health Genomics, Western Australian Department of Health), and Kate Bushby, (Newcastle University) can be found here.

Biomarkers and their use in monitoring disease progression in rare diseases 

Biomarkers are particularly important for monitoring disease progression and therapeutic efficacy in rare diseases where cohort sizes are small and clinical phenotypes can be highly variable. Two research groups have published results from proteomic studies in an attempt to identify and validate blood borne biomarkers in patients with muscular dystrophy.

Ayoglu et al (2014) used a multiplexed antibody suspension bead array to perform proteomic profiling of 345 samples collected by the EU-FP7 BIO-NMD consortium partners. Results from this study identified the presence of a number of proteins including carbonic anhydrase III (CA3), myosin light chain 3 (MYL3), malate dehydrogenase 2 (MDH2) and electron transfer flavoprotein A (ETFA) that were present in the blood from DMD patients at a higher level than healthy controls.

In a separate paper by Martin et al (2014), a MS-based bottom-up pipeline approach was used to identify and validate serum biomarkers for the progression of DMD. Results showed a significant increase in Fibronectin levels in patients with DMD when compared to other muscular dystrophies such as Becker muscular dystrophy or Bethlem myopathy. Furthermore, elevated levels were also observed in longitudinal studies in DMD patients over duration of 4 years.

Collectively, the results from these publications suggest protein biomarkers found in blood and serum have the potential to be used as indicators of disease phenotype and severity which make them key candidates for novel diagnostic clinical tests and management of muscular dystrophies.

Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants

Duchenne muscular dystrophy (DMD) is characterised by muscle degeneration with variable progression towards loss of ambulation. Recent studies have suggested such differences in disease progression could be associated with genetic modifiers in the SPP1 and LTBP4 loci. In this paper, van den Bergen et al (2014) present the results from a large multicentre genetic association study of SNPs at the LTBP4 and SPP1 loci in patients with DMD. Results demonstrated a correlation between disease progression and the IAAM haplotype of the LTBP4 gene (rs2303729, rs1131620, rs1051303 and rs10880). However, as opposed to previous studies, no significant correlation between SNP rs28357094 in the SSPP1 gene and disease progression was observed. These results highlight the importance of replicating genetic association studies in order to qualify prognostic biomarkers, and also that future DMD trials should consider the LTBP4 haplotype prior to stratification of patients. 

EuroBioBank: 10 year review

Established in 2001 and operational in 2003, the EuroBioBank (EBB) network was established under the European Commission’s 5th framework programme, with the aim of improving accessibility of biospecimens and associated data on rare diseases. The network is made up of 16 partners from 8 European countries (Belgium, France,Germany, Hungary, Italy, Malta, Slovenia and Spain). In this review, Mora et al., 2014 have provided an overview of the past 10 years of EuroBioBank from the start-up and consolidation phases to current partnerships with RD-Connect and BBMRI-ERIC. 


Rare Disease Biobanks are invited to publish their collection the RD-Connect Catalogue

Access to high-quality biological materials is essential for research on rare diseases. The new RD-Connect Catalogue of rare disease biological samples aims to unite rare biomaterials by facilitating sample search, and creating a strong network of rare disease biobanks in Europe. The sample catalogue, together with patient databases and clinical bioinformatics, is one of the three essential assets of the RD-Connect integrated platform.

The IT infrastructure of the sample catalogue has been built, and we are now inviting rare disease biobanks to register their interest to publish their sample collection. The RD-Connect ID-Card is the entry point where biobanks can be enlisted and be a part of the rare disease network. Many benefits that bring a positive impact on the operations of the rare disease biobanks are available when they participate:

• Visibility: listing biosamples via RD-Connect can lead to increased visibility in a global setting and increased sample acquisition and sharing. These facilitate the establishment of new collaborations and enhance networking activities in the field of RD research. 

• Impact: maximise the impact of biobanks by connecting clinical to bioinformatics data generated from patients’ biological samples. Pooling of data supports the advancement of research in rare diseases.

• Quality standards & Training: biobanks will have access to training material on SOPs and policies according to international standards. These materials contribute the quality system and operational development of rare disease biobanks.

• Interoperability: particular attention is paid to the crosstalk of the sample catalogue with the US and Australian counterparts to ensure the platform is internationally interoperable. System optimisation is essential for resource sharing in the rare disease context.

Existing European rare disease biobank networks such as EuroBioBank and TNGB (Telethon Network of Genetic Biobanks) are associated partners of RD-Connect, where they have contributed the establishment of data models and workflows. In addition, means to standardize biosample and data sharing procedures on ethical and legal grounds has been carefully considered within RD-Connect with dialogues from patient associations and international bodies. Biobanks that participate in the RD-Connect catalogue will become a part of a dynamic community that seeks to bring advancements in rare disease research.


How to make your registry or biobank visible: the RD-Connect registry and biobank ID-Cards 

The RD-Connect Catalogue will contain information about new and already existing databases, registries and biobanks in a system known as ID-Cards. Each ID-Card will contain the following information:

• general overview and organisation

• diseases collected

• standards and procedures

• accessibility of data

• study documents e.g. study protocol, case report form, informed consent template and data access agreement.

The 'diseases collected' section will be of particular interest to rare disease researchers as it contains a "disease matrix" which lists the ORPHAcodes, OMIM numbers and synonyms, for every disease. It also provides information about the number of registered cases or samples available within a database, registry or biobank. This section will be continually updated by the database curators to ensure information is current and accurate.

Over the past 24 months, ID-Cards have been created for a list of 97 pioneering rare disease registries and databases which were invited to participate. Potential biobanks are welcome to register their interest via the propose page of the catalogue, where after registration, a secure access to the evaluation form will be generated for the new proposed Biobank.


How rare disease biobanks can contribute to the sample catalogue

In order to ensure the high quality of biological samples in research, all biobanks wishing to list biosamples via RD-Connect will be subjected to a simple assessment process before formal acceptance to the RD-Connect Catalogue and platform.

In this phase of the project, rare disease biobanks are invited to register their interest by filling an online assessment form via the ID-Card. A number of European rare disease biobanks that have been identified during a mapping exercise will receive an invitation email that contains a direct link to their assessment page. Spontaneous candidacies are welcome via the propose page of the catalogue, where after registration, a secure access to the evaluation form will be generated for the new proposed Biobank.

A panel of internationally recognised biobanking expert will consider the biobanks against a set of criteria to ensure minimum quality assurance is met. Only rare disease biobanks, or biobanks with a clear focus on rare diseases, will be accepted on to the RD-Connect catalogue. The quality assurance criteria cover the implementation of Quality Standards, SOPs, adherence to ELSI principles, and a minimum informatics setup. More details on these criteria can be found on the RD-Connect website. Biobanks will receive feedback within two months of submission on the outcome of the review.

Once accepted onto the RD-Connect catalogue, the biobank will have access to the catalogue database, where its own basic information can be inserted or curated. The biobank will at this point on be visible and be listed as one of the contributing RD-Connect biobanks. During the next phase the biobanks will submit the minimal dataset on their sample collection to the platform, and begin sharing samples via the RD-Connect catalogue.


BBMRI-ERIC as a resource for pharmaceutical and life science industries

BBMRI-ERIC (Biobanking and Biomolecular Resources Research Infrastructure - European Research Infrastructure Consortium, BBMRI- ERIC) is an infrastructure with sustainable funding from European member states covering a wide spectrum of biobanks including bioresources for all diseases, irrespective of whether they are considered common or rare, as well as population-based cohort studies.

As described in a recent review by van Ommen et al., 2014, BBMRI-ERIC biobanks offer a wide range of biospecimens that cover the whole drug discovery and development process, from early stage research, to pre-clinical through to clinical. BBMRI-ERIC is therefore a relevant and important source for researchers working in academia and industry. BBMRI-ERIC are also establishing Expert Centers which will act to provide a trusted, operational middle ground between the public and private sectors to ensure the provision of high quality biological material and associated data. It is hoped that these Expert Centers will act as new ‘highways’ to promote transnational research.

EuroBioBank is now a member of  BBMRI-ERIC  thanks to its partnership with RD-Connect. BBMRI-ERIC has acknowledged that rare diseases and rare disease biobanking presents its own unique set of challenges and procedures. For this reason BBMRI-ERIC is considering the establishment of a common service for rare disease to specifically address issues related to RD biobanks.

Prof. Jan-Eric Litton, BBMRI-ERIC Director General and RD-Connect partner, has been working with RD-Connect with the aim of forming an official partnership between the RD-Connect and BBMRI-ERIC over the coming months.


Biobanking: the importance of patient support and participation 

More and more, rare disease patient organisations recognise the importance of access to high-quality human biological materials as essential for advancing research. As a result, many have facilitated the collection of biosamples by supporting biobanking activities, starting their own biobanks or playing a special role in liaising with their patient members in guiding their participation.

As such, one major task of the work on biobanking in RD-Connect focuses on facilitating the process of collecting biosamples from rare disease patients by collaborating with patient organisations. With the support of EURORDIS, patient organisations across Europe will be invited to sign agreements with the RD-Connect biobanks to encourage participation. By entering such non-binding, but formal, agreements patient groups can receive information and advice about biobanking research to help encourage their constituents to participate. This process is inspired by an existing alliance between UNIAMO (Italian Rare Disease Alliance) and Telethon Network of Genetic Biobanks (TNGB) that has already demonstrated success.

During a recent BBMRI-NL conference on November 28th, one session titled Biobanking 2.0: towards big data, open access and involving participants proposed a discussion on the importance of keeping a two way dialogue (via personal or overall feedback on findings, access to results, etc.) with patients to increase buy-in from the patient community. Marieke van Meel, member of the RD-Connect Patient Advisory Group and EURenOmics Scientific Advisory Board presented on behalf of NephcEurope about best practices in retaining patient support of participants in biobanking research.

If you are a patient organisation interested in more information about collaborating with RD-Connect biobanks, please contact Matt Johnson,matt.johnson@eurordis.org


Upcoming events

For further information on future events please visit the events page on the RD-Connect website.

20th-23th April 2015, Prague, Czech Republic

A 4-day course on Next Generation Sequencing in Prague - Czech Republic in the period of 20-23 April 2015. The focus of the course is on clinical diagnostics using exome/ genome sequencing, variant identification and analysis including afternoon practicals (limited places). The course will also include an evening symposium co-organised by
Milan Macek; “Genotranslation: Interpretation of genome data in diagnostics” Some of the topics to be covered:

- Whole Genome Sequencing

- Targeted sequencing

- Wet lab procedures

- Annotation and priorization of variants

- Next Generation Sequencing: problems and solutions

- Data analysis

- Afternoon practicals (limited places available - participants should bring their own laptop).


Why did I get this email?

You received this email because you are associated with RD-Connect, EURenOmics or Neuromics or because you signed up online. We will send out around one email per month with news of relevance to these projects and to IRDiRC. If you don't want to receive any further newsletters, you can unsubscribe using the link below. If you're reading this online or if it was forwarded by a friend, you can sign up to future editions here.