The RD‐Connect Genome‐Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases

Human Mutation, vol. 43, pp. 717–733

Abstract

Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes.

Authors 50

1. Steven Laurie

   Barcelona Institute of Science and Technology · Centre for Genomic Regulation

   Affiliation as printed

   CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

   CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

2. Davide Piscia

   Barcelona Institute of Science and Technology · Centre for Genomic Regulation

   Affiliation as printed

   CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

   CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

3. Leslie Matalonga

   Barcelona Institute of Science and Technology · Centre for Genomic Regulation

   Affiliation as printed

   CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

   CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

4. Alberto Corvò

   Barcelona Institute of Science and Technology · Centre for Genomic Regulation

   Affiliation as printed

   CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

   CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

5. Carles García

   Barcelona Institute of Science and Technology · Centre for Genomic Regulation

   Affiliation as printed

   CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

   CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

6. Marcos Fernández-Callejo

   Barcelona Institute of Science and Technology · Centre for Genomic Regulation

   Affiliation as printed

   CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

   CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

7. Carles Hernandéz-Ferrer

   Barcelona Institute of Science and Technology · Centre for Genomic Regulation

   Affiliation as printed

   CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

   CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

8. Cristina Luengo

   Barcelona Institute of Science and Technology · Centre for Genomic Regulation

   Affiliation as printed

   CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

   CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

9. Anastasios Papakonstantinou

   Barcelona Institute of Science and Technology · Centre for Genomic Regulation · Centro Nacional de Análisis Genómico

   Affiliation as printed

   CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

   Centro Nacional de Análisis Genómico

   CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

10. Joan Protassio

    Barcelona Institute of Science and Technology · Centre for Genomic Regulation

    Affiliation as printed

    CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

11. Daniel Picó

    Barcelona Institute of Science and Technology · Centre for Genomic Regulation

    Affiliation as printed

    CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

12. Rachel Thompson

    Children's Hospital of Eastern Ontario

    Affiliation as printed

    Children's Hospital of Eastern Ontario Research Institute

    Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada

13. Raúl Tonda

    Barcelona Institute of Science and Technology · Centre for Genomic Regulation

    Affiliation as printed

    CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

14. Mónica Bayés

    Barcelona Institute of Science and Technology · Centre for Genomic Regulation

    Affiliation as printed

    CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

15. Gemma Bullich

    Barcelona Institute of Science and Technology · Centre for Genomic Regulation

    Affiliation as printed

    CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

16. Jordi Camps

    Barcelona Institute of Science and Technology · Centre for Genomic Regulation

    Affiliation as printed

    CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

17. Ida Paramonov

    Barcelona Institute of Science and Technology · Centre for Genomic Regulation

    Affiliation as printed

    CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

18. Jean-Rémi Trotta

    Barcelona Institute of Science and Technology · Centre for Genomic Regulation

    Affiliation as printed

    CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

19. Ángel Miguel Alonso

    Universidad Pública de Navarra (UPNA) · Navarrabiomed

    Affiliation as printed

    Navarrabiomed; Universidad Publica de Navarra

20. Marcella Attimonelli

    University of Bari Aldo Moro

    Affiliation as printed

    University of Bari Department of Biosciences Biotechnology and Pharmacological Bioscience

    Department of Biosciences, Biotechnology and Biopharmaceutics, University of A. Moro, Bari, Italy

21. Christophe Béroud

    Inserm · Hôpital de la Timone · Centre de Génétique Médicale de Marseille

    Affiliation as printed

    Marseille Medical Genetics, INSERM UMR_S910; APHM, Hôpital d'Enfants de la Timone, Déparement de Génétique Médicale

22. Virginie Bros‐Facer

    European Organisation for Rare Diseases

    Affiliation as printed

    EURORDIS, Paris

    EURORDIS-Rare Diseases Europe

23. Orion J. Buske
    Affiliation as printed

    Phenotips, Toronto

    Phenotips, Toronto, Ontario, Canada

24. Andrés Cañada

    Spanish National Cancer Research Centre

    Affiliation as printed

    Centro Nacional de Investigaciones Oncologicas

25. José M. Fernández

    Barcelona Supercomputing Center

    Affiliation as printed

    Barcelona Supercomputing Center

    Barcelona Supercomputing Center, Spain

26. MATS G. HANSSON

    Uppsala University

    Affiliation as printed

    Uppsala Universitet Medicinska fakulteten,

    Centre for Research Ethics & Bioethics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden

27. Rita Horváth

    University of Cambridge

    Affiliation as printed

    University of Cambridge Cambridge Centre for Brain Repair

    Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom

28. Julius O.B. Jacobsen

    Queen Mary University of London · William Harvey Research Institute

    Affiliation as printed

    Queen Mary University of London ‐ Charterhouse Square Campus

    Queen Mary University of London, William Harvey Research Institute, London, UK

29. Rajaram Kaliyaperumal Aachen

    Leiden University Medical Center

    Affiliation as printed

    Leiden University Medical Center

    Leiden University Medical Center, Leiden, The Netherlands

30. Séverine Lair
    Affiliation as printed

    Interactive Biosoftware, Rouen

31. Luana Licata

    University of Rome Tor Vergata · Human Technopole

    Affiliation as printed

    University of Rome Tor Vergata, Department of Biology

    Department of Biology, University of Rome Tor Vergata, Rome, Italy

    Fondazione Human Technopole, Milan, Italy

32. Pedro Lopes
    Affiliation as printed

    IEETA

    IEETA, Aveiro, Portugal

33. Estrella López Martín

    Instituto de Salud Carlos III · Centre for Biomedical Network Research on Rare Diseases · Instituto de Investigación de Enfermedades Raras

    Affiliation as printed

    Instituto de Salud Carlos III, Institute of Rare Diseases Research (IIER) & Centre for Biomedical Network Research on Rare Diseases

    Institute of Rare Diseases Research, Spanish Undiagnosed Rare Diseases Cases Program (SpainUDP) & Undiagnosed Diseases Network International (UDNI), Instituto de Salud Carlos III, Madrid, Spain

34. Deborah Mascalzoni

    Uppsala University · University of Lübeck

    Affiliation as printed

    Centre for Research Ethics and Bioethics

    University of lubeck Institute of biomedicine

    Uppsala Universitet Medicinska fakulteten,

35. Lucía Monaco

    Fondazione Telethon

    Affiliation as printed

    Fondazione Telethon, Milan

    Fondazione Telethon, Milan, Italy

36. Luis Pérez Jurado

    Universitat Pompeu Fabra · Instituto de Salud Carlos III · Centre for Biomedical Network Research on Rare Diseases · Hospital Del Mar · Municipal Institute for Medical Research · Hospital del Mar Research Institute

    Affiliation as printed

    ISCIII, CIBERER

    Institut Hospital del Mar d'Investigacions Mediques, Servei de Genètica, Hospital del Mar

    Universitat Pompeu Fabra, Unitat de Genètica, Departament de Ciències Experimentals i de la Salut

    Genetics Service, Hospital del Mar & Hospital del Mar Research Institute (IMIM), Barcelona, Spain

37. Manuel Posada de la Paz

    Instituto de Salud Carlos III · Centre for Biomedical Network Research on Rare Diseases · Instituto de Investigación de Enfermedades Raras

    Affiliation as printed

    Instituto de Salud Carlos III (ISCIII), SpainRDR and CIBERER, Instituto de Investigación en Enfermedades Raras (IIER)

    Institute of Rare Diseases Research, Spanish Undiagnosed Rare Diseases Cases Program (SpainUDP) & Undiagnosed Diseases Network International (UDNI), Instituto de Salud Carlos III, Madrid, Spain

38. Jordi Rambla

    Universitat Pompeu Fabra · Barcelona Institute of Science and Technology · Centre for Genomic Regulation

    Affiliation as printed

    Center for Genomic Regulation, EGA

    Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain

    Universitat Pompeu Fabra (UPF), Barcelona, Spain

39. Ana Rath

    Inserm

    Affiliation as printed

    INSERM, US14

    INSERM, US-14 Orphanet, Paris, France

40. Olaf Horst Riess

    University of Tübingen

    Affiliation as printed

    University of Tubingen Institute for Medical Genetics and Applied Genomics

41. Peter N. Robinson

    The Jackson Laboratory for Genomic Medicine · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Charite Universitätsmedizin Berlin, The Jackson Laboratory

    The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA

42. Damian P. Smedley

    Queen Mary University of London · William Harvey Research Institute

    Affiliation as printed

    Barts and The London School of Medicine and Dentistry William Harvey Research Institute

    Queen Mary University of London Barts and The London School of Medicine and Dentistry

43. Dylan Spalding

    CSC - IT Center for Science (Finland)

    Affiliation as printed

    CSC IT Center for Science Ltd

44. Peter A.C. ’t Hoen

    Radboud University Medical Center · Radboud Institute for Molecular Life Sciences

    Affiliation as printed

    Radboud Universiteit Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences

    Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

45. Ana Töpf

    Newcastle upon Tyne Hospitals NHS Foundation Trust · Newcastle University

    Affiliation as printed

    The John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University

    John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK

46. Irina T. Zaharieva

    University College London

    Affiliation as printed

    UCL Great Ormond Street Institute of Child Health, Dubowitz Neuromuscular Centre

    UCL Great Ormond Street Institute of Child Health, Dubowitz Neuromuscular Unit, London, UK

47. Holm Graeßner

    Universitätsklinikum Tübingen · ERN-RND · University of Tübingen

    Affiliation as printed

    University Hospital Tubingen Centre for Rare Diseases

    University of Tubingen Institute for Medical Genetics and Applied Genomics

    European Reference Network for Rare Neurological Diseases

48. Ivo Glynne Gut

    Universitat Pompeu Fabra · Barcelona Institute of Science and Technology · Centre for Genomic Regulation · Centro Nacional de Análisis Genómico

    Affiliation as printed

    Centro Nacional de Análisis Genómico Baldiri Reixac

    Pompeu Fabra University

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

    Universitat Pompeu Fabra (UPF), Barcelona, Spain

49. Hanns Lochmüller

    University of Ottawa · Children's Hospital of Eastern Ontario · Ottawa Hospital · Barcelona Institute of Science and Technology · Centre for Genomic Regulation · uOttawa Brain and Mind Research Institute

    Affiliation as printed

    Children's Hospital of Eastern Ontario Research Institute

    Ottawa Hospital, Division of Neurology, Department of Medicine

    University of Ottawa, Brain and Mind Research Institute

    Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

    Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada

    Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada

50. Sergi Beltrán corresponding

    Universitat Pompeu Fabra · Barcelona Institute of Science and Technology · Centre for Genomic Regulation · Universitat de Barcelona

    Affiliation as printed

    CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

    Pompeu Fabra University

    Universitat de Barcelona, Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia

    CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

    Universitat Pompeu Fabra (UPF), Barcelona, Spain