Community Research and Development Information Service - CORDIS

FP7

RD-CONNECT Report Summary

Project ID: 305444
Funded under: FP7-HEALTH
Country: United Kingdom

Periodic Report Summary 4 - RD-CONNECT (RD-CONNECT: An integrated platform connecting registries, biobanks and clinical bioinformatics for rare disease research)

Project Context and Objectives:
RD-Connect is a global research and infrastructure resource for rare diseases (RD). Set up to overcome the siloing, fragmentation and inaccessibility of datasets from different projects, it links omics data with phenotypic data and information in registries and biobanks at both an individual-patient and whole-cohort level to enable researchers to analyse their own data and gain a complete view of their disease and patient population of interest. Data shared through RD-Connect is accessible beyond the usual institutional and national boundaries and researchers across the world can benefit from the opportunity to work with others with an interest in the same field, relate human phenotypes to a particular gene or pathway of interest, pool data to create larger cohorts, find confirmatory cases, and access samples for further study.
The project’s objectives are to develop:
• an integrated platform to host and analyse data from RD omics research projects
• clinical bioinformatics tools for analysis and integration of molecular and clinical data to discover new disease genes, pathways and therapeutic targets in RD
• common standards and data elements for RD patient registries
• common standards and a sample-level catalogue for RD biobanks
• best ethical practices and recommendations for a regulatory framework for linking medical and personal data related to RD
RD-Connect was launched on 1 November 2012 and this report focuses on the project’s fourth year of operation, from November 2015 to October 2016.
The integrated platform developed by RD-Connect brings together omics data and clinical data from participating projects with tools and services to analyse this data online. The central portal available at http://platform.rd-connect.eu provides access to the genomics analysis interface, the PhenoTips database that stores human phenotype ontology-coded phenotypic profiles for the individuals whose genomic data is accessible in the system, and the catalogue of biobanks and patient registries, which provides a searchable interface summarising each resource and the cohorts it contains. The biosample catalogue that allows drill-down to details of individual samples hosted in participating biobanks will become fully operational in 2017.
Interactions with the ESFRI research infrastructures, in particular BBMRI and ELIXIR, have been further strengthened in 2016. BBMRI-ERIC is now a full partner of RD-Connect, which is a valuable means of ensuring synergy in overlapping activities relating to the existing BBMRI common services for ELSI and IT, as well as for working on sustainability for RD-Connect’s biobanking resources through a potential BBMRI common service for rare disease. Thanks to the fact that a large number of RD-Connect partners are also ELIXIR members active in the ELIXIR-EXCELERATE project, many activities relating to the rare disease use case and the interoperability and training work packages are carried out together with RD-Connect, and this has been extremely beneficial for both sides.
RD-Connect’s mechanism for sharing and analysis of rare disease genomic data begins with submission of the raw .bam or .fastq files, which is essential in order to allow data from multiple sequencing providers to be processed through a standard pipeline to ensure comparability. The raw data are stored for long-term access at the European Genome-phenome Archive (EGA), a secure, controlled-access repository, while the processed data are made accessible online for real-time analysis in the RD-Connect genomics analysis interface. The standard analysis pipeline for aligning, variant calling and annotating raw exome and genome data has been applied to 1142 samples to date (November 2016) and the fully annotated results are available to authorised users through the online interface. Several thousand more datasets are planned for submission in the coming year, now that the platform is open for submission of data from all rare disease projects.

Project Results:
During the fourth year of the project, the genomics analysis interface has become a mature tool for diagnosis and gene discovery. The user-friendly online system allows users to analyse their own data as well as data submitted by others. A researcher can study one or multiple individuals and filter and refine the results by mode of inheritance, population frequencies, in silico pathogenicity prediction tools etc. After performing the initial filtration, extensive further details are provided for each variant. A new update in 2016 also allows users to search by gene across all cases in the system in order to find others in which the same gene is affected, which enables “matchmaking” to find confirmatory cases for gene discovery and allows researchers with an interest in a particular gene to find corresponding human cases in which the gene is affected.
RD-Connect continues to collaborate with other international data sharing initiatives, including the Global Alliance for Genomics and Health’s “beacon” API and Matchmaker Exchange. In a collaboration with BBMRI-LPC, RD researchers were provided with exome sequencing at no cost through transnational access, but the project conditions mandated that biosamples must be made accessible through EuroBioBank biobanks and phenotypic data must be submitted to the RD-Connect PhenoTips instance, while the resulting sequencing data will be automatically submitted to the RD-Connect platform. This not only allows the researchers themselves to analyse their own cases but also ensures that the samples and data will be accessible to other researchers in future. The datasets from this project, numbering almost 1000 cases, will be accessible within the genomics analysis interface from January 2017.
The 2016 activities relating to patient registries have focused extensively on enabling data linkage and the principle of making registry data Findable, Accessible, Interoperable and Reusable (FAIR). A successful proof of concept showing that it is possible to enable questions across biobanks and registries by making data machine readable at the source was demonstrated and a comprehensive cross-project data linkage plan has now been developed together with ELIXIR and BBMRI. The providers of a number of software solutions for patient registries are engaged with this process, receiving support from data linkage experts in making their solutions into FAIR data points that can expose their data for queries in a secure fashion.
A second focus has been on improving the visibility of RD biobanking and registry resources. To this end, RD-Connect has developed two complementary systems: ID Cards, a catalogue providing information about existing registries and biobanks across Europe and beyond, and the sample catalogue, a database providing searchable access to biosample records at an individual sample level.
For biobanking, technical activities this year focused on importing data from EuroBioBank and integration with the ID-Cards system and the main platform, including preparation for the hosting of both systems within the main platform infrastructure in Barcelona. Discussions were initiated to ensure the tools under development are interoperable, in particular with the BBMRI-ERIC IT Common Service. A further major achievement is the agreement between RD-Connect and EuroBioBank that EuroBioBank will be the de facto biobank network for RD-Connect.
In addition to the central resources offered through the platform interface, RD-Connect partners have also developed a number of bioinformatics tools to assist researchers in omics analysis and therapeutic target identification. At this point in the project, the tools are continuing to be further developed and their features improved and extended. Work on omics data integration has also continued via exemplar integration projects for pathway and network analysis, and through the joint multi-omics task force established across RD-Connect, NeurOmics and EURenOmics.

Potential Impact:
ELSI experts within RD-Connect have been actively engaged in establishing the ethical framework under which RD-Connect can enable sharing of sensitive human data in a secure and ethical fashion. Building on the preceding work within the project, a Code of Practice based on legal requirements and ethical principles as well as patient and scientific needs has been drafted. All principal investigators requesting access to the RD-Connect platform must accept the Code of Practice on their own behalf and that of their team by signing an Adherence Agreement. While established specifically for RD-Connect, the Code of Practice has relevance for other disease areas. The Code may also be of relevance in relation to the application of the new EU General Data Protection Regulation (GDPR), and RD-Connect will participate in a BBMRI-led consortium to develop a Code of Conduct related to the GDPR.
At the end of its fourth year, RD-Connect is a recognised resource within the rare disease genomic research community. The maturity of the central RD-Connect platform as a tool for genomic analysis has facilitated many new data-focused collaborations in 2016. Poster and platform presentations at a number of international conferences, both disease-specific and genetics-focused, have encouraged researchers to submit data to the system, and around 2000 further datasets from new projects are set to arrive in early 2017.
In the public health sphere, the establishment of European Reference Networks has the potential for substantial synergy with RD-Connect. While ERNs have primarily a healthcare focus, they must also establish research aims, and the majority of ERN expert centres do themselves have substantial research and diagnostic activity and would value the opportunity to collaborate with RD-Connect to share research-related clinical, biosample and omics data. RD-Connect has offered all ERN coordinators the opportunity to work together on such activities and will make its services available to all ERNs successful in the first call.
Sustaining the infrastructural resources generated through RD-Connect has been an important topic in 2016 and must continue to be consolidated in the coming year. RD-Connect partners are involved in or leading a number of upcoming grant applications in the H2020 Health and Infrastructures work programmes, some of which may provide sustainability for elements of the central platform and data linkage resources. Other sustainability mechanisms are being actively pursued, including fee-for-service and cost-recovery models, as well as deeper integration with the ESFRI research infrastructures where appropriate.
RD-Connect has continued to interact closely with the IRDiRC, with RD-Connect coordinator Hanns Lochmüller chairing the IRDiRC Interdisciplinary Scientific Committee and a number of RD-Connect partners contributing to IRDiRC committees and engaging with various task forces. At EU level a number of RD-Connect partners are also engaged in the ongoing discussions relating to potential new funding mechanisms for rare disease, and here we are strongly advocating not only the use where appropriate of existing infrastructures such as RD-Connect and the ESFRI research infrastructures, but also of establishing the primacy of data sharing and interoperability as one of the cornerstones of the initiative.
Overall, at the end of its fourth year, RD-Connect is consolidating its position as a key player within the rare disease genomics field. 2017 must see further use of the platform by new projects, including further successes in terms of gene discovery from its use as a primary analysis interface. The successful implementation of the data linkage plan to enable cross-resource queries through making databases interoperable at the source is another important goal that will drive forward interoperability of patient registries and biobanks across the field.

List of Websites:
http://rd-connect.eu

Contact

Rory Deane, (Grants and Contracts Manager)
Tel.: +44 191 2824514
Fax: +44 191 2824524
E-mail
Record Number: 195907 / Last updated on: 2017-03-14
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