6 June 2014  ●   Issue 6

Joint projects meeting - Heidelberg, Germany

RD-Connect, Neuromics and EURenOmics held their annual joint meeting at Heidelberg University, Germany at the end of February 2014. The meeting provided over 300 attendees including project partners, associated partners and committee members with an opportunity to report on progress and plan for future work. Other participants included members of the Joint Patient Advisory Council (RD-PAC) as well as several representatives from industry who provided sponsorship for the meeting. Industry representatives were able to attend the joint sessions and also contributed to the discussion during the industry forum.

During the meeting each project had the opportunity to discuss how they are individually and collaboratively addressing several challenges in the field of rare disease research:

  • establishing and providing access to harmonized data and samples,
  • performing the molecular and clinical characterization of rare diseases,
  • boosting translational, preclinical and clinical research,
  • and streamlining ethical and regulatory procedures.

Results from the first year are already contributing towards the two main  International Rare Diseases Research Consortium (IRDIRC) objectives of delivering 200 new therapies and means to diagnose most rare diseases by the year 2020. Through whole-exome sequencing, Neuromics and EURenOmics have identified a number of potential novel disease causing genes. Major progress has also been achieved in understanding some of the underlying causes of disease, as demonstrated for example in spinal muscular atrophy (SMA) and membranous nephropathy (MN).

Advances in the identification of new biomarkers and validation or improvement of existing ones have also begun. Samples have been collected and methods established to conduct biomarker studies for Huntington’s disease (HD), spinocerebellar ataxia (SCA), fronto-temporal lobe dementia and hereditary spastic paraplegia. Proof of concept for certain therapeutic approaches have been initiated such as antisense oligonucleotide-mediated exon skipping for HD, SCA and Duchenne muscular dystrophy.

For RD-Connect, the primary focus of the year has been to ensure that the project is aligned with the needs of researchers submitting data to the platform. Progress is being made towards integrating biomaterials and phenotypic data through the development of a searchable online catalogue for biosamples and agreement on the use of standard terminology for describing a patient’s phenotype using the Human Phenotype Ontology (HPO). A technical meeting (jamboree) at the end of June 2014 will work on variant analysis use cases from the associated projects and aims to prove the utility of version 1 of the RD-Connect platform for analysis of variants.

As the IRDiRC mandates that all data generated by the research projects it funds is released for the benefit of the wider research community, Neuromics and EURenOmics have committed to securely archiving their data in the European Genome-phenome Archive (EGA) at the European Bioinformatics Institute (EBI) and sharing it within the RD-Connect system. The first datasets have been uploaded and policies for how data can be shared with the research community have been established across projects. One important feature of the data sharing policy is that it ensures that investigators are allowed time to analyse their own results prior to sharing with others, but nevertheless ensures that all data is released according to a defined timeline, whilst still protecting patient confidentiality.

Posters from the joint meeting available online

The three associated projects are committed to making as much information as possible publicly available to the broader community and a number of posters from the Heidelberg poster session have therefore been made available via figshare, an online system for sharing research data and results. To add your poster to this list, upload it to figshare and contact the RD-Connect coordination office. Uploaded posters are given a DOI, which means they can be cited in other publications.

Click here to view the posters.

Training material available online

As part of the joint project meeting in Heidelberg eleven training courses were offered to all RD-Connect, NeurOmics and EURenOmics attendees. Over 180 delegates attended sessions on bioinformatics, ontologies, linked data, next generation sequencing analysis and troubleshooting, biomarkers, data sharing and various software tools including COEUS, PhenoTips, PhenomeCentral, deCODE Clinical Sequence Analyzer, Alamut, Genomatix, YABI and Nephromine. Feedback was very positive and further training sessions will be organised at future meetings.

Training presentations, including video recordings of Bioinformatics for Beginners (Jan Taylor, The Nowgen Centre, Manchester) and PhenoTips and PhenomeCentral (Michael Brudno, Hospital for Sick Children, University of Toronto) are available here.

9th IRDiRC executive meeting - Berlin, Germany

The Executive Committee of the International Rare Diseases Research Consortium (IRDiRC) met on 7-8 May 2014 in Berlin, Germany. Launched in 2011, IRDiRC is an umbrella organization for more than 30 participating global funding organizations and their aligned research projects. IRDiRC's two main objectives by the year 2020 are to deliver 200 new therapies for rare diseases and the means to diagnose most rare diseases. Three scientific committees (Diagnostics, Interdisciplinary and Therapeutics) advise the Executive Committee (comprised of representatives of each of the funders) on the best way forward to meet the IRDiRC objectives.

The Diagnostics Scientific Committee is focused on enabling the diagnosis of most rare diseases by 2020. To meet this goal an understanding of the mechanism of most rare diseases and facilitation of clinical translation of genomic sequencing for patients with rare diseases is required. A number of standards, tools and infrastructures must be put in place and made available to facilitate discovery and collaboration to meet this objective. Most urgent amongst these are a standard ontology to facilitate sharing of rare disease phenotypes and a large-scale platform to share rare disease phenotypes and genotypes to enable discovery of new disease genes.

The Therapeutics Scientific Committee is focused on reaching the target of 200 new therapies for rare diseases by 2020. The committee should develop a minimum but comprehensive set of recommendations engaging all relevant stakeholders in alternative pathways to develop medicines from early stage research right up to their regulatory approval. These include adaptive clinical trial design and statistical methods, alternatives to animal models, promotion of research on biomarkers and further used on existing ones, optimal use of scientific guidance by regulatory agencies. The committee works closely with the two other scientific committees for an integrated approach while working through working groups in relevant areas such as orphan drugs & regulatory affairs, biomarkers for disease progression and therapy response, chemically derived products including repurposing of medicines, biotechnology derived products including cell & gene therapies.

The Interdisciplinary Scientific Committee closely collaborates with the other scientific committees and is concerned with cross-cutting themes relevant for RD research, in particular ethics and governance, data sharing and bioinformatics, patient registries and natural history studies, and biobanks. Contributions to the IRDiRC road map were proposed that include infrastructural support in these areas to underpin the research and remove bottlenecks towards the ambitious IRDiRC goals.

The next Executive Committee meeting will be held prior to the 2nd IRDiRC conference in Shenzhen, China during November 2014. Previous IRDiRC executive committee reports can be found here.

Informed consent guidelines workshop - Rome, Italy

A workshop dedicated to the informed consent process in RD-Connect was organised by the National Center for Rare Diseases at the Istituto Superiore di Sanità in Rome. During this workshop, participants were invited to discuss the common values and principles on informed consent and data sharing in the rare disease field.

A number of new complexities in the informed consent process have become apparent in recent years due to an increase in the exchange of data inside and outside international research consortia. An increased exchange in data results in the need to provide research participants with additional information for them to be able to make an informed choice about participation and requires coordination and comparability between different research centres worldwide.

Previous work on informed consent in international consortia suggests, amongst other things, that in order to create useful guidelines: (i) core consent elements should be defined and agreed by all members and (ii) guidelines should be wide enough to be adaptable to the differing ethical, legal and cultural norms of their members.

In RD-Connect, the Guidelines on Informed Consent will have to consider the needs of B-Projects (NeurOmics and EURenOmics) and of other candidate registries and biobanks. Some of these projects already have in place procedures and templates for data collection, adapted to different contexts. Others are just starting and have thus the possibility to adopt new templates and procedures for the informed consent process well suited to the new needs of international data sharing and to the new promises of -omics research.

The workshop described and made proposals for the informed consent process according to different situations. For example:

- old collections obtained with / without informed consent and the possibility to include them in RD-Connect by using old or new informed consent; update of information with the possibility to opt out; waiver of consent but REC approval; anonomysation.

- new collections of existing study projects, gathered using old informed consent forms

- new research projects for which new information sheets and consent templates can be created ex-novo.

A specific section of the workshop was dedicated to the informed consent of children.

The two day workshop was structured into oral presentations and discussions followed by working group sessions. All the material collected during the workshop will be used to prepare the Guidelines on Informed Consent which will be made available through the RD-Connect website.

Further reading: Wallace SE, Knoppers BM. Harmonised consent in international research consortia: an impossible dream? Genomics, Society and Policy 2011;(7):35-46

Rare disease patients give their views on the RD- Connect platform - Berlin, Germany

Thirty-four rare disease advocates took part in focus groups to give their views on various aspects of linking and sharing data internationally for rare disease research during the EURORDIS Membership Meeting in Berlin in May. While the views of the general public and those with common diseases are widely known, the specific views of rare disease patients on this subject are not documented.  The groups were preceded by two talks: in the first Justin Paschall outlined how the RD- Connect platform would work practically and in the second, Simon Woods provided background to the ethics legislation and governance that exists today.

Focus group participants discussed two scenarios designed to explore their thoughts and feelings about consent issues and around having their health and genomic data widely shared outside of their local care provider. They discussed a wide range of issues including: what we can learn from historical precedents; the responsibilities of researchers; who should have access to collections and how this should be managed; and how researchers can improve communication with participants. Patients were from across Europe with a few from North America.

More focus groups are forthcoming in June in Barcelona, after which the data will be analysed, written up and the results made widely available. In addition this knowledge of the rare disease patient’s viewpoint will be widely disseminated throughout RD Connect, Neuromics and EURenOmics and will be used in educational activities for researchers attached to these three projects.

Neuromics newsletter available on-line

NeurOmics is an EU-funded research project that addresses ten rare neurodegenerative and neuromuscular disorders. Next generation whole-exome sequencing and detailed clinical information is now being combined and used to improve the diagnoses and understanding of these diseases with an aim to developing future therapies - contributing to the IRDiRC goals of delivering 200 new therapies for rare diseases by 2020.

This current newsletter focuses on the project's achievements in its first year of operation and explains some of the techniques used to analyse the samples donated by patients. It also touches upon a number of new genes that have been discovered as a result of the project, gives an update on biomarkers and concludes with a look to what the coming months will hold for the project.

 Download the newsletter here.


Upcoming events

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

Advanced NGS Course: RNA-seq data analysis (4th edition)

7-9 July, Berlin, Germany Leiden University Medical Center, Leiden, Netherlands 

The BioSB research school and partners LUMC and ErasmusMC are organising a 3-day course on RNA-seq data analysis from 7-9 July, 2014. This is an advanced course for people with experience in Next Generation Sequencing. The course will consist of seminars and hands-on command line, Galazy and R practicals and will cover the analysis pipeline for differential transcript expression and variant calling. Examples will be taken from human and mouse studies. The course does not cover prokaryotic RNA profiling nor plant-and metagenomics aspcts.

ISMB 2014

11-15 July 2014, John B. Hynes Memorial Convention Center, Boston, USA

The Intelligent Systems for Molecular Biology (ISMB) conference brings together computational biology researchers of every career stage from around the world. Hosted by the International Society for Computational Biology (ISCB), ISMB has grown over 22 years to become the world’s largest bioinformatics/computational biology conference.

ISMB attracts top international scientists in the life sciences and offers a strong scientific program and the broadest scope of any international bioinformatics/computational biology. Topics of interest include sequence analysis, evolution and phylogeny, comparative genomics, protein structure, molecular and supramolecular dynamics, molecular evolution, gene regulation and transcriptomics, RNA biology, proteomics, systems biology, ontologies, databases and data integration, text mining and information extraction, and human health.

 Phenotype Day

 12 July 2014, John B. Hynes Memorial Convention Center, Boston USA

Phenotype Day will bring researchers together from different disciplines to share information about phenotype resources and issues as well as experiences with defining, representing, processing and using phenotype data.

The systematic description of phenotype variation has gained increasing importance since the discovery of the causal relationship between a genotype placed in a certain environment and a phenotype. It plays not only a role when accessing and mining medical records but also for the analysis of model organism data, genome sequence analysis and translation of knowledge across species. Accurate phenotyping has the potential to be the bridge between studies that aim to advance the science of medicine (such as a better understanding of the genomic basis of diseases), and studies that aim to advance the practice of medicine (such as phase IV surveillance of approved drugs).

The Phenotype day is a joint special day of the Bio-Ontologies and BioLINK Special Interest Groups. Selected submissions accepted for the phenotype day will be published as a special edition of the Journal of Biomedical Semantics.

Molecular Neurology and Therapeutics

July 12 - July 18, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

This popular Wellcome Trust course provides a concentrated examination of the molecular basis of neurological diseases and strategies being developed for their treatment. The course curriculum offers a unique opportunity to learn the latest concepts associated with the study of both rare and common neurological disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, stroke, the ataxias, Fragile X syndrome and others. Participants will discuss in detail the strengths and weaknesses of the experimental evidence underlying our current understanding of these diseases and how this knowledge is being applied to develop small molecule and nucleic acid based therapies. Participants will also have the opportunity to share their work with faculty and other trainees, as well as engage in informal discussions throughout the course.

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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.