An interconnected data infrastructure to support large-scale rare disease research

作者：Lennart Johansson, Steven Laurie, Dylan Spalding, Spencer Gibson, David Ruvolo, Coline Thomas, Davide Piscia, Fernanda de Andrade, Gerieke Been, Marieke Bijlsma, Han G. Brunner, Sandi Cimerman, Farid Yavari Dizjikan, Kornelia Ellwanger, Marcos Fernández-Callejo, Mallory Freeberg, Gert‐Jan van de Geijn, Roan Kanninga, Vatsalya Maddi, Mehdi Mehtarizadeh, Pieter B. Neerincx, Stephan Ossowski, Ana Rath, Dieuwke Roelofs-Prins, Marloes Stok-Benjamins, K. Joeri van der Velde, Colin Veal, Gerben van der Vries, Marc Wadsley, Greg Warren, Birte Zurek, Thomas Keane, Holm Graeßner, Sergi Beltrán, Morris A. Swertz, Anthony J. Brookes, Olaf Rieß, Tobias B. Haack, Holm Graeßner, Birte Zurek, Kornelia Ellwanger, Stephan Ossowski, German Demidov, Marc Sturm, Julia M. Schulze‐Hentrich, Rebecca Schüle, Jishu Xu, Christoph Keßler, Melanie Kellner, Matthis Synofzik, Carlo Wilke, Andreas Traschütz, Lüdger Schöls, Holger Hengel, Holger Lerche, Josua Kegele, Peter Heutink, Han G. Brunner, Hans Scheffer, Nicoline Hoogerbrugge, Alexander Hoischen, Peter A.C. ’t Hoen, Lisenka E.L.M. Vissers, Christian Gilissen, Wouter Steyaert, Karolis Šablauskas, Richarda M. de Voer, Erik-Jan Kamsteeg, Bart van de Warrenburg, Nienke van Os, Iris te Paske, Erik Janssen, Elke de Boer, Marloes Steehouwer, Burcu Yaldız, Tjitske Kleefstra, Anthony J. Brookes, Colin Veal, Spencer Gibson, Vatsalya Maddi, Mehdi Mehtarizadeh, Umar Riaz, Greg Warren, Farid Yavari Dizjikan, Thomas Shorter, Ana Töpf, Volker Straub, C. Marini Bettolo, Jordi Díaz‐Manera, Sophie Hambleton, Karin R. Engelhardt, Jill Clayton‐Smith, Siddharth Banka, Elizabeth Alexander, Adam Jackson, Laurence Faivre, Christel Thauvin, Antonio Vitobello, Anne‐Sophie Denommé‐Pichon, Yannis Duffourd, Ange‐Line Bruel, Christine Peyron, Aurore Pélissier, Sergi Beltrán, Marta Gut, Steven Laurie, Davide Piscia, Leslie Matalonga, Anastasios Papakonstantinou, Gemma Bullich, Alberto Corvò, Marcos Fernández-Callejo, Carles Hernandéz-Ferrer, Daniel Picó, Ida Paramonov, Hanns Lochmüller, Gulcin Gumus, Virginie Bros‐Facer, Ana Rath, Marc Hanauer, David Lagorce, Oscar Hongnat, Maroua Chahdil, Emeline Lebreton, Giovanni Stévanin, Alexandra Dürr, Claire-Sophie Davoine, Léna Guillot‐Noël, Anna Heinzmann, Giulia Coarelli, Gisèle Bonne, Teresinha Evangelista, Valérie Allamand, Isabelle Nelson, Rabah Ben Yaou, Corinne Métay, B. Eymard, Enzo Cohen, António Atalaia, Tanya Stojkovic, Milan Macek, Marek Turnovec, Dana Thomasová, Radka Pourová Kremliková, Věra Franková, Markéta Havlovicová, Petra Lišková, Pavla Doležalová, Helen Parkinson, Thomas Keane, Mallory Freeberg, Coline Thomas, Dylan Spalding, Peter N. Robinson, Daniel Danis, Glenn Robert, Alessia Costa, Christine Patch, Mike Hanna, Henry Houlden, Mary M. Reilly, Jana Vandrovcová, Stéphanie Efthymiou, Heba Morsy, Elisa Calì, Francesca Magrinelli, S. M. Sisodiya, Jonathan D. Rohrer, Francesco Muntoni, Irina Zaharieva, Anna Sárközy, Vincent Timmerman, Jonathan Baets, Geert de Vries, Jonathan De Winter, Danique Beijer, Peter De Jonghe, Liedewei Van de Vondel, Willem De Ridder, Sarah Weckhuysen, Vincenzo Nigro, Margherita Mutarelli, Manuela Morleo, Michele Pinelli, Alessandra Varavallo, Sandro Banfi, Annalaura Torella, Francesco Musacchia, Giulio Piluso, Alessandra Ferlini, Rita Selvatici, Francesca Gualandi, Stefania Bigoni, Rachele Rossi, Marcella Neri, Stefan Aretz, Isabel Spier, Anna Katharina Sommer, Sophia Peters, Carla Oliveira, José Garcia‐Pelaez, Rita Barbosa‐Matos, Celina São José, Marta Ferreira, Irene Gullo, Susana Fernandes, Luzia Garrido, Pedro Ferreira, Fátima Carneiro, Morris A. Swertz, Lennart Johansson, Joeri K. van der Velde, Gerben van der Vries, Pieter B. Neerincx, David Ruvolo, Kristin M. Abbott, Wilhemina S. Kerstjens Frederikse, Eveline Zonneveld-Huijssoon, Dieuwke Roelofs-Prins, Mariëlle van Gijn, Sebastian Köhler, Alison Metcalfe, Alain Verloes, Séverine Drunat, Delphine Héron, Cyril Mignot, Boris Keren, Jean‐Madeleine de Sainte Agathe, Caroline Rooryck, Didier Lacombe, Aurélien Trimouille, Manuel Posada de la Paz, Eva Bermejo, Estrella López‐Martín, Beatriz Martínez Delgado, F. Javier Alonso García de la Rosa, Andrea Ciolfi, Bruno Dallapiccola, Simone Pizzi, Francesca Clementina Radio, Marco Tartaglia, Alessandra Renieri, Simone Furini, Chiara Fallerini, Elisa Benetti, Peter Balicza, Mária Judit Molnár, Aleš Maver, Borut Peterlin, Alexander Münchau, Katja Lohmann, Rebecca Herzog, Martje G. Pauly, Alfons Macaya, Ana Cazurro‐Gutiérrez, Belén Pérez-Dueñas, Francina Munell, Clara Franco‐Jarava, Laura Batlle-Masó, Anna Marcé‐Grau, Roger Colobrán, A. Nascimento Osorio, Daniel Natera‐de Benito, Hanns Lochmüller, Rachel Thompson, Kiran Polavarapu, Bodo Grimbacher, David Beeson, Judith Cossins, Peter Hackman, Mridul Johari, Marco Savarese, Bjarne Udd, Rita Horváth, Patrick F. Chinnery, Thiloka Ratnaike, Fei Gao, Katherine Schon, Gabriel Capellá, Laura Valle, Elke Holinski‐Feder, Andreas Laner, Verena Steinke‐Lange, Evelin Schröck, Andreas Rump, A. Nazlı Başak, Dimitri Hemelsoet, Bart Dermaut, Nika Schuermans, Bruce Poppe, Hannah Verdin, Davide Mei, Annalisa Vetro, Simona Balestrini, Renzo Guerrini, Kristl G. Claeys, Gijs W.E. Santen, Emilia K. Bijlsma, Mariëtte J.V. Hoffer, Claudia Ruivenkamp, Kaan Boztuǧ, Matthias Haimel, Isabelle Maystadt, Isabell Cordts, Marcus Deschauer, Ioannis Zaganas, Evgenia Kokosali, Mathioudakis Lambros, Athanasios Evangeliou, Martha Spilioti, Elisabeth Kapaki, Mara Bourbouli, Pasquale Striano, Federico Zara, Antonella Riva, Michele Iacomino, Paolo Uva, Marcello Scala, Paolo Scudieri, Maria-Roberta Cilio, Evelina Carpancea, Chantal Depondt, Damien Lederer, Yves Sznajer, Sarah Duerinckx, Sandrine Mary, Christel Depienne, Andreas Roos, Patrick May · 发表于：GigaScience · 年份：2024 · DOI：10.1093/gigascience/giae058 · 被引用次数：9 · 研究领域：Genomics and Rare Diseases、Cancer Genomics and Diagnostics、Genomic variations and chromosomal abnormalities

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.