DEL 10.5 Report on the State of the Art of existing resources EJP RD European Joint Programme on Rare Diseases H2020-SC1-2018-Single-Stage-RTD SC1-BHC-04-2018 Rare Disease European Joint Programme Cofund Grant agreement number 825575 Del 10.5 Report on the State of the Art of existing resources in Europe Organisation name of lead beneficiary for this deliverable: Partner 1 – INSERM Contributors: EMBL-EBI, RaDiCo Due date of deliverable: month 09 Dissemination level: Public 1 DEL 10.5 Report on the State of the Art of existing resources Table of contents 1 Background ..................................................................................................................... 3 1.1 Resources fragmentation ....................................................................................... 3 1.2 Researcher’s needs ................................................................................................. 3 2 Objectives ....................................................................................................................... 5 3 Methods ........................................................................................................................... 5 3.1 Working group creation .......................................................................................... 5 3.2 Identification of infrastructural components necessary for research for diagnostic improvement and therapeutic development ................................ 6 3.3 Benchmarking and prioritisation of existing resources........................................ 6 3.3.1 2017 survey on RD resources .............................................................................. 7 3.3.2 2019 survey on RD resources .............................................................................. 7 4 Results ............................................................................................................................... 9 Resources assessment ................................................................................................ 11 5 Conclusions ................................................................................................................... 18 ANNEX I. List of research resources for rare diseases ................................................. 20 ANNEX II. List of WG-identified resources contacted for the 2017 survey ............... 44 ANNEX III. List of questions asked in the 2017 survey ................................................... 47 ANNEX IV. List of questions asked in the 2019 survey ................................................... 49 ANNEX V. Results of the 2017 survey on RD resources ................................................ 50 ANNEX VI. Results of the 2019 survey on RD resources ................................................ 52 ANNEX VII. List of members of the 2017 working group ................................................ 58 List of figures Figure 1. Survey ERNs: Is this resource of utmost importance in your research? (ERNs survey 2019) .............................................................................................................. 4 Figure 2. RD research resources landscape (see ANNEX I for resources details). .......... 8 Figure 3. Expected effect of EJP RD on research efforts. ................................................. 19 List of tables Table 1. Evaluation of resources based on the 2017 and 2019 surveys on resources .. 17 2 DEL 10.5 Report on the State of the Art of existing resources 1 Background 1.1 Resources fragmentation Resources relevant for rare disease (RD) research already in existence, such as knowledge bases, databases, registries, tools, and infrastructures, are significant. However, despite the multitude of efforts, most of them allowed by European funding, in providing the RD research community with appropriate tools and platforms, research advancements in the RD field remain hampered by the duplications of efforts and fragmentation of resources making their efficient use challenging1. The aim of collaborative work in Pillar 2 is geared towards decreasing fragmentation and maximizing European capacity to enable better and more efficient research on RD by bringing the interdisciplinary key players, their assets and know-how together with the end-users. The foreseen EJP RD Virtual Platform aims at decreasing fragmentation and overlaps by building a single access point to find and query resources, and to provide data analysis facilities. Not only will it be made possible by coordinated access to the most important catalogues for RD (e.g. Orphanet, RD- Connect biobanks and patient registry catalogues) and tools (customized ELIXIR bio.tools), as well as to the main data deposition and analysis resources for genomics, phenomics and multi-omics data, but access to infrastructures providing support to clinical and translational research will be improved. This will be ultimately accessible to the whole RD community. 1.2 Researcher’s needs The priority of the EJP RD is that needs of researchers are met but these needs must be identified first. In 2019, the EJP RD Pillar 2 sent a survey to European Reference Networks (ERNs) in order identify the RD researchers’ needs (WP10.2.2; Deliverable 10.1). Two hundred and ninety-one responses were received (response rate of 31%) that allowed Pillar 2 to characterize current RD research as follows: 1. Almost all (97%) ERN units do clinical research, and many do also translational and basic research. 2. The main purposes of research are (in order of importance): (a) improve diagnostics (73%), (b) identify disease modifiers (69%), (c) develop novel therapies (64%), and (d) develop disease models (22%). 1 Thompson, R., Johnston, L., Taruscio, D., Monaco, L., Béroud, C., Gut, I. G., et al. (2014). RD- Connect: an integrated platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research. Journal of General Internal Medicine, 29 Suppl 3(S3), S780–7. http://doi.org/10.1007/s11606-014-2908-8 3 DEL 10.5 Report on the State of the Art of existing resources 3. Researchers use mostly the following data types: (a) patient information (95%), (b) natural history (91%), (c) biological samples (85%), (d) electronic medical health records (81%), (e) phenotypes (73%), (f) medical images (71%). 4. Out of 165 respondents, 79% of researchers do not deposit their -omics data in open or controlled access resources (esp. due to legal jurisdiction and complexity of use issues). 5. ICD, OMIM, ORDO, and HPO are the main ontologies/standards used to annotate data. 6. Very few researchers (13%) have FAIRified (<1%) or are in the process of FAIRifying data (12%), due in part to insufficient understanding of FAIRification as well as technical barriers. 7. Services of utmost importance for research are: (a) support to conduct clinical trials (69%), (b) facility to find patient registries (63%), (c) support to conduct translational research (53%), (d) facility to find biobanks/biosamples/cell lines (45%), (e) facility to find software and tools (40%), and (f) databases of re-usable data related to RDs (-omics) (30%). 8. Research infrastructures and resources of utmost importance for research are: (a) international/national registries (84% of respondents), Orphanet catalogue of RD resources (61% of respondents), ERDRI (50% of respondents), RaDiCo (26% of respondents), RD-Connect sample and registry and biobank finder (17% of respondents), BBMRI-ERIC directory of biobanks (15% of respondents). 9. ERNs often do not know about existing research infrastructures or resources (see Figure 1). This survey made clear that researchers need resources to be better exposed, ordered, and accessible to save them time, money, workforce, and reduce overall data management and analysis hassles. Yes No Unknown No reply Is this resource of utmost importance in your research? ERNs survey 2019 Registries RD-Connect G-P Orphanet ORDO HPO (inter)national Analysis PhenoMeNal neXtProt UniprotKB DECIPHER EUPID Yes No Unknown No reply Is this resource of utmost importance in your research? ERNs survey 2019 BBMRI RD Connect Are resouErcLIXeIRs visible enouIgNFhR?AFRONTIER ECRIN Funded by the European Union GA n°825575 hPSCreg EATRIS Cellosaurus RaDiCo ERDRI Funded by the European Union GA n°825575 Figure 1. Survey ERNs: Is this resource of utmost importance in your research? (ERNs survey 2019). (See ANNEX I for resources details.) 4 DEL 10.5 Report on the State of the Art of existing resources 2 Objectives The aim of this report is threefold: (1) to provide an overview of existing resources that can be valuable for RD research, (2) to assess them in terms of readiness for this use, and (3) to estimate the value that the planned EJPRD Virtual Platform can add to these resources by making them usable cooperatively. This report is not intended to expose the Pillar 2 strategy, which has been detailed in the deliverable 10.1. It focuses on infrastructural RD research resources such as platforms, tools, and standards. Resources of expertise, such as ERNs, and data sources such as individual registries were considered out scope for this deliverable and therefore excluded. These resources can still be found in the list of research resources for RD provided in ANNEX I. 3 Methods 3.1 Working group creation The overall concept of the Pillar 2 is to improve the research cycle from bedside to bench and back again. That is the aim of the planned EJP RD Virtual Platform (VP) to be created within the Pillar. Three steps were