[en] The Solve-RD project brings together clinicians, scientists, and patient representatives from 51 institutes spanning 15 countries to collaborate on genetically diagnosing ("solving") rare diseases (RDs). The project aims to significantly increase the diagnostic success rate by co-analyzing data from thousands of RD cases, including phenotypes, pedigrees, exome/genome sequencing, and multiomics data. Here we report on the data infrastructure devised and created to support this co-analysis. This infrastructure enables users to store, find, connect, and analyze data and metadata in a collaborative manner. Pseudonymized phenotypic and raw experimental data are submitted to the RD-Connect Genome-Phenome Analysis Platform and processed through standardized pipelines. Resulting files and novel produced omics data are sent to the European Genome-Phenome Archive, which adds unique file identifiers and provides long-term storage and controlled access services. MOLGENIS "RD3" and Café Variome "Discovery Nexus" connect data and metadata and offer discovery services, and secure cloud-based "Sandboxes" support multiparty data analysis. This successfully deployed and useful infrastructure design provides a blueprint for other projects that need to analyze large amounts of heterogeneous data.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Johansson, Lennart F ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Laurie, Steve ; Centro Nacional de Análisis Genómico, C/Baldiri Reixac 4, 08028, Barcelona, Spain ; Universitat de Barcelona (UB), Gran Via de les Corts Catalanes, 585, L'Eixample, 08007, Barcelona, Spain
Spalding, Dylan ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CV10 1SD, UK
Gibson, Spencer ; Department of Genetics, Genomics and Cancer Sciences, University of Leicester, University Road, Leicester, Leicester, LE1 7RH, UK
Ruvolo, David ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Thomas, Coline ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CV10 1SD, UK
Piscia, Davide ; Centro Nacional de Análisis Genómico, C/Baldiri Reixac 4, 08028, Barcelona, Spain ; Universitat de Barcelona (UB), Gran Via de les Corts Catalanes, 585, L'Eixample, 08007, Barcelona, Spain
de Andrade, Fernanda ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Been, Gerieke ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Bijlsma, Marieke; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Brunner, Han ; Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, 6525 GA, The Netherlands ; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, P.O.Box 9103, Nijmegen, 6500 HD, The Netherlands ; Department of Clinical Genetics, Maastricht University Medical Centre, P. Debyelaan 25, Maastricht, 6229 HX, The Netherlands
Cimerman, Sandi ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Dizjikan, Farid Yavari; Department of Genetics, Genomics and Cancer Sciences, University of Leicester, University Road, Leicester, Leicester, LE1 7RH, UK
Ellwanger, Kornelia ; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstraße 7, Tübingen 72076, Germany
Fernandez, Marcos ; Centro Nacional de Análisis Genómico, C/Baldiri Reixac 4, 08028, Barcelona, Spain ; Universitat de Barcelona (UB), Gran Via de les Corts Catalanes, 585, L'Eixample, 08007, Barcelona, Spain
Freeberg, Mallory ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CV10 1SD, UK
van de Geijn, Gert-Jan ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Kanninga, Roan; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Maddi, Vatsalya ; Department of Genetics, Genomics and Cancer Sciences, University of Leicester, University Road, Leicester, Leicester, LE1 7RH, UK
Mehtarizadeh, Mehdi; Department of Genetics, Genomics and Cancer Sciences, University of Leicester, University Road, Leicester, Leicester, LE1 7RH, UK
Neerincx, Pieter ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Ossowski, Stephan ; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstraße 7, Tübingen 72076, Germany ; Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, Geschwister-Scholl-Platz, Tübingen 72074, Germany
Rath, Ana ; INSERM, US-14 Orphanet, 96 rue Didot, Paris 75014, France
Roelofs-Prins, Dieuwke; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Stok-Benjamins, Marloes ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
van der Velde, K Joeri ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Veal, Colin ; Department of Genetics, Genomics and Cancer Sciences, University of Leicester, University Road, Leicester, Leicester, LE1 7RH, UK
van der Vries, Gerben ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Wadsley, Marc ; Department of Genetics, Genomics and Cancer Sciences, University of Leicester, University Road, Leicester, Leicester, LE1 7RH, UK
Warren, Gregory; Department of Genetics, Genomics and Cancer Sciences, University of Leicester, University Road, Leicester, Leicester, LE1 7RH, UK
Zurek, Birte ; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstraße 7, Tübingen 72076, Germany
Keane, Thomas ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CV10 1SD, UK
Graessner, Holm ; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstraße 7, Tübingen 72076, Germany ; Centre for Rare Diseases, University of Tübingen, Geschäftsstelle Eisenbahnstraße 63, Tübingen 72072, Germany
Beltran, Sergi ; Centro Nacional de Análisis Genómico, C/Baldiri Reixac 4, 08028, Barcelona, Spain ; Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona (UB), Diagonal, 643, 08028, Barcelona, Spain
Swertz, Morris A ; Department of Genetics, University of Groningen, University Medical Center Groningen, HPC CB50, P.O. Box 30001, Groningen, 9700 RB, The Netherlands
Brookes, Anthony J ; Department of Genetics, Genomics and Cancer Sciences, University of Leicester, University Road, Leicester, Leicester, LE1 7RH, UK
MAY, Patrick ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Horizon 2020 Framework Programme Instituto de Salud Carlos III CINECA
Funding text :
We acknowledge all Solve-RD partners (see Solve-RD consortium) and all hospitals and patients that shared data. We acknowledge Olaf Riess as Solve-RD project coordinator. We acknowledge RedIris (https://www.rediris.es/rediris/) for enabling data transfer from the data providers to GPAP. The Solve-RD project has received funding from the European Union's Horizon2020 research and innovation program under grant agreement 779257. The RD-Connect Genome-Phenome Analysis Platform received funding from EU projects RD-Connect, Solve-RD, and EJP-RD (grants FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grants PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinform\u00E1tica, INB), and ELIXIR Implementation Studies. The UMCG VRE and RD3 received funding from the EU projects Solve-RD, EJP-RD, and CINECA Project (H2020 779257, H2020 825575, H2020 825775, respectively) and NWO VIDI grant number 917.164.455.The Solve-RD project has received funding from the European Union\u2019s Horizon 2020 research and innovation program under grant agreement 779257. The RD\u2010Connect Genome\u2010Phenome Analysis Platform received funding from EU projects RD\u2010Connect, Solve-RD, and EJP-RD (grants FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grants PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinform\u00E1tica, INB), and ELIXIR Implementation Studies. The UMCG VRE and RD3 received funding from the EU projects Solve-RD, EJP-RD, and CINECA Project (H2020 779257, H2020 825575, H2020 825775, respectively) and NWO VIDI grant number 917.164.455.
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