25 November 2013   ●   Issue 2

Save the date for the next joint meeting!

RD-Connect, EURenOmics and Neuromics are holding their next joint meeting in Heidelberg, Germany, in February 2014.

23 February from 14:00: training courses open to all partiicpants
24-26 February: cross-project scientific conference
26 February afternoon: further training courses

All project partners and advisory board members are invited to save the date in their diaries now.

The agenda for the joint meeting will have a strong scientific focus, including plenary, breakout and poster sessions, sessions for early stage researchers, and many opportunities for interaction.

Eleven training courses will be offered. They will include dedicated sessions on bioinformatics, ontologies, linked data, next generation sequencing analysis and troubleshooting, biomarkers, data sharing and various bioinformatics tools e.g. COEUS, PhenoTips, PhenomeCentral, deCODE, Alamut, Genomatix, YABI and Nephromine. Registration for the meeting will open in December and participants will be asked to register for the training sessions at that point.

For further information, contact Emma Heslop.

Focus on ontologies

Enabling data sharing: two publications highlight ethical and legal questions to be addressed

Harmonizing terminology for describing phenotypes: ontology systems come together

It is increasingly recognized that advances in sequencing technology do not replace the need for detailed clinical analysis of patients with rare diseases. On the contrary, deep phenotyping is more important than ever in order to interpret whole exome and genome sequencing results. However, where clinical notes are on paper systems in hospitals, or where doctors enter free text in electronic systems, the power of computers cannot be leveraged to support analysis.

Phenotype ontologies are an attempt to standardize the collection of phenotypic data in order to make it accessible to computer analysis. Several different systems exist and are used in databases, registries and electronic health records around the world. However, the lack of compatibility between these systems and the lack of terminology specific enough for rare disease has been a challenge for a number of years. A new initiative called the International Consortium for Human Phenotype Terminologies (ICHPT) is working to standardize a core set of terminology across the major different systems in use. At a workshop preceding the American Society of Human Genetics meeting in Boston in October, representatives of the Human Phenotype Ontology, PhenoDB, Orphanet, Elements of Morphology and others came together to align over 2300 core terms across all phenotype ontologies. All tools using these ontologies will map to these terms to allow cross-compatibility between systems, and SNOMed-CT will also be requested to implement the full set of aligned terms. Where ontologies contain more detailed terms at a finer level of granularity, these terms will map "up" to the broader aligned terms. From early 2014 further information will be available at www.ichpt.org

Ensuring omics data sharing systems make use of standardized terminology in this way is critical to maximize the potential of the data from next-generation sequencing. The RD-Connect system is using the Human Phenotype Ontology as its primary mechanism for harmonizing clinical data entry and will also ensure full compatibility with the aligned terms.

Standardizing clinical data collection using HPO and PhenoTips

With over 10,000 classes (terms) describing human phenotypic abnormalities and over 13,000 subclass relations between the classes, together with extensive annotation and cross-referencing with other ontologies, the Human Phenotype Ontology (HPO) is a leading system for standardized collection of clinical information about patients with rare diseases. Many research and clinical projects in the field including the Decipher database and the Deciphering Developmental Disorders project at Sanger, the NIH Undiagnosed Diseases Program, GWAS Central, and the FORGE and Care for Rare projects use the HPO for all their clinical data entry. In collaboration with RD-Connect, Neuromics and EURenOmics are also now implementing the HPO to enable standardized cross-cohort comparisons and filtering. EURenOmics are developing a central HPO-based "phenome" database to collate clinical information from their cohort of kidney disease patients. A new collaboration between RD-Connect, Neuromics and the developers of a user-friendly HPO-based software solution called PhenoTips has enabled development of standardized online forms for clinicians to enter disease-specific phenotypic information for neuromuscular and neurodegenerative diseases. As part of the collaboration with HPO developers, terminology workshops with expert clinicians are planned for 2014 in order to augment the HPO, which is still under active expansion, with further phenotypic classes for neuromuscular, neurodegenerative and renal diseases.

"Matchmaking" to find confirmatory cases: systems developers work on interconnection

As the use of next generation techniques increases, individual diagnostic and research labs around the world are collecting increasing numbers of unsolved cases for which final diagnosis cannot be made due to lack of a "second family" or confirmatory case. Several groups are actively working on systems for "exome/genome matchmaking" to enable an environment that allows cases with candidate genes/variants to be brought together with other unsolved cases though phenotype and genotype matching algorithms. At the American Society of Human Genetics meeting in Boston, a meeting initiated by Heidi Rehm and Kym Boycott brought together interested parties plus representatives of systems including PhenomeCentral, PhenoDB Gene Matcher, LOVD VIP, Decipher, ClinGen, Cafe Variome and others, with the aim of interconnecting efforts to increase the likelihood of success. As an outcome of this meeting, two working groups were established. The first, a systems development/API working group, will work on technical solutions for making the existing systems more interoperable. The second, a "matchmaking tiers" working group, will come up with definitions and recommendations for different levels or "tiers" of data sharing, from a minimal sharing level that might enable some matchmaking goals to be achieved, to a more extensive level that would also enable other important scientific research on submitted data. Data shared within the RD-Connect system will also be made available securely for this matchmaking goal.

For further information please contact Heidi Rehm or Rachel Thompson.

Meeting reports and updates

EuroBioBank annual meeting provides updates on RD-Connect integration

Biobanking activities within RD-Connect are a collaboration between EuroBioBank, a pan-European biobanking network specifically focused on rare diseases, and BBMRI, the Biobanking and Biomolecular Resources Research Infrastructure. The 11th EuroBioBank Annual General Assembly was held in Milan on 14 October 2013.

The 21 biobanks within EuroBioBank are now supplying approx. 74,000 samples through the central online catalogue. A total of 209 publications acknowledging EuroBioBank have now been published since the network began. Other discussions focused on ISO certification for biobanks and for the entire EuroBioBank network, cost recovery options for use of biomaterials, informed consent issues, and integration with registries containing clinical data.

In a dedicated RD-Connect session, RD-Connect coordinator Hanns Lochmüller updated the General Assembly on RD-Connect's progress and on the IRDiRC consortium and the ongoing discussions taking place at the European level on the possibility to create an ERIC dedicated to RDs. 

Additional updates were received from RD-Connect task leaders and partners:

  • Heimo Muller, from Kurt Zatloukal's team at Medical University of Graz (Austria), provided updates on RD-Connect’s strategy for the mapping of rare disease biobanks in Europe and abroad, and the development of a questionnaire, based on the BBMRI exercise, to survey RD Biobanks
  • RD-Connect partner Manuel Posada from Instituto de Salud Carlos III (Spain) described the plans for interoperability with rare disease registries and implementation of a GUID (Globally Unique Identifier)
  • Marco Crimi and Marina Mora from Fondazione Telethon and the Telethon Network of Genetic Biobanks described the procedures and policies for the collection and distribution of RD biospecimens.
  • Lucia Monaco, Fondazione Telethon, presented an overview of the main objectives and tasks for the second year of the RD-Connect biobank workpackage. Specifically, the development of the core searchable catalogue of samples and the setting up of procedures for new incoming biobanks, such as application procedures and training.

The General Assembly unanimously agreed that EuroBioBank should apply to become an associated partner of RD-Connect. 

RD-Connect Exec discuss data sharing and GUID

The RD-Connect Executive Management Committee (EMC) held a face-to-face meeting in Leiden on 10 October 2013. Eight members of the EMC, representing all of the work packages, were present, along with the coordination office and management team. 

The meeting provided the project's steering committee with the opportunity to discuss important strategic issues. The main emphasis of the meeting was on the work relating to the development of the data platform and its integration with registries and biobanks. Data transfer from Neuromics, EURenOmics and other IRDiRC projects and the establishment of the Global Unique Identifier were also key topics of discussion.

RD-Connect partner EBI reported that preparations to upload the first set of exome data from Neuromics to the European Genome-phenome Archive are almost complete, and a similar pilot is also ongoing with EURenOmics. The data sharing process has been approved by the collaborating projects and precise agreements on timelines for data release are currently being established, as well as the convening of data access committees who will grant access to the data in both the EGA and RD-Connect systems. The first batch of data will be transferred within the next few weeks and once the process is validated and proved to be working effectively will be opened up to other IRDiRC projects.

The EMC also recognized that it is important to solve the issues relating to the development of a Globally Unique Identifier to link different datasets belonging to a single individual. The EMC discussed the options currently available to the project and will make a decision, in collaboration with all WP leaders and guidance from the patient community, on which system to adopt.

Update on the Global Alliance

As previously reported, in June this year RD-Connect joined over 100 institutions worldwide in signing up to the Global Alliance, an initiative that was established to help encourage sharing of linked clinical and genomic data. Over the past few months progress has been made to drive the alliance forward and onto the next phase of development.

The Translational Steering Committee and five interim working groups have been launched to work on a range of topics. Each group has at least one leader who is a member of the Transitional Steering Committee, and includes a diverse team of alliance partners chosen based on their experience and expertise. 

Regulatory Working Group
Chair: Bartha Knoppers
Co-Chair: Kazuto Kato
Co-Chair: Partha Majumder

Genomic Data Working Group
Chair: Paul Flicek

Security Working Group
Co-Chair: David Haussler
Co-Chair: Richard Durbin

Clinical Interface Working Group
Chair: Charles Sawyers

The official launch of the alliance is planned for early 2014, which will also coincide with a meeting of all the major partners.

RD-Connect Stakeholder Conference discusses the regulatory hurdles and challenges of data sharing for genomic research in rare disease

Enabling data sharing for the benefit of research while still adequately protecting patient data is a challenge that must be addressed if progress is to be made in rare disease research. A Stakeholder Conference was organized in Brussels on 17-18 October 2013 to discuss issues surrounding regulatory hurdles for international data-sharing in rare disease research.  Prior to the conference, the Patient Advisory Council (PAC) met to discuss the patient perspective on data sharing as well as other issues. During the two day meeting, there was a particular focus on issues surrounding informed consent, data-sharing governance and transparency, with a special focus on implications for industry involvement. The conference brought together experts including patients and patients’ representatives, industry representatives, academics and clinicians in order to identify the hurdles hampering research. A round table process took place in order to identify hurdles and possible solutions. Agreements on the type of consent required to maximize the use of data and biospecimens was obtained, but further work is needed to establish consensus on the information process related to consent and the strategy for follow up information.

A report based on the meeting will be prepared for publication.

IRDiRC interdisciplinary committee works on "road map" for IRDiRC research and funding

The 4th meeting of the IRDiRC Interdisciplinary Scientific Committee (ISC) took place in Montreal, Canada on 17 and 18 October 2013, hosted by Bartha Knoppers and chaired by Hanns Lochmüller. Previous meetings were dedicated to setting up IRDiRC working groups and defining policies and guidelines for IRDiRC researchers and funding organizations. At the Montreal meeting, the ISC discussed recommendations for the IRDiRC road map to advise the IRDiRC executive committee. The objective of the road map is to set scientific priorities and define milestones/key issues in a proactive way.  The overarching objectives of IRDiRC are to develop 200 new therapies for RD and diagnosing most RD by 2020. The ISC has received expert input from its 4 working groups (WG ethics and governance; WG data sharing and bioinformatics; WG registries and natural history; WG biobanks). Similarly, a set of recommendations is expected from  the diagnostic and therapeutic science committees.

2nd International Workshop on Rare Diseases and Orphan Drug Registries (Rome, 21-22 October, 2013)

The 2nd Rare Diseases and Orphan Drug Registries workshop, a follow-up to the event held in October 2012, was organized by the EU-funded EPIRARE project. EPIRARE aims to build consensus and synergies for the development of an EU platform for rare disease registries and address relevant regulatory, ethical and technical issues associated with the registration of RD patients in Europe and at the international level.

The workshop intended to give an update on the moving context of RD registries and to present and discuss possible uses and outputs of a European Platform for rare disease registries. Moreover, case studies of relevant international rare disease registries were presented, with updates on their recent activity and with the lessons learned in their particular study field.

Part of the debate was dedicated to the Personal Data Protection regulations, the revision of which is on-going in the European Parliament. The importance of promoting registration of rare disease patients and the special needs of rare disease registries were explained in the video Half of a Score. Moreover, EPIRARE communicated the launch of an on-line petition (Don’t stop research on rare diseases!), which you are kindly invited to sign, with the aim of avoiding the dramatic impact that this revision may have on health research. Translations of the video and the petition, as well as the Workshop abstract book and the slides of the presentations are available on the EPIRARE website.



Our online events listing details events organized by RD-Connect as well as selected relevant external events. 

7th European Conference on Rare Diseases and Orphan Products

8-10 May 2014, Berlin, Germany

The three-day European Conference on Rare Diseases and Orphan Products (ECRD) will provide an opportunity for patients, policy makers, healthcare professionals, industry, payers, regulators, researchers and academics working in the rare disease field to meet and exchange information and ideas. With over 100 speakers and numerous professionals in attendance, the annual conference will cover the latest research, developments in new treatments and information regarding innovations in health care, social care and support at both the European and national levels.

Workshop: Implementation of clinical genetic databases

17 December 2013, Manchester, UK

This workshop will provide training for current and future implementers of accessible or shared databases for collection of actionable clinical genotype and phenotype data. Training will cover:

  • Tools and resources used in the process of creating and running a database
  • Standards important for databasing
  • Strategies for successful planning and implementation of a database project

The workshop will include practical computer-based training and group exercises to explore the resources available and the issues relating to sustainable database implementation.

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