Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
13
10
2020
accepted:
26
02
2021
revised:
18
01
2021
pubmed:
3
6
2021
medline:
24
3
2022
entrez:
2
6
2021
Statut:
ppublish
Résumé
Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics.
Identifiants
pubmed: 34075210
doi: 10.1038/s41431-021-00852-7
pii: 10.1038/s41431-021-00852-7
pmc: PMC8440686
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1337-1347Subventions
Organisme : Medical Research Council
ID : MR/S002065/1
Pays : United Kingdom
Investigateurs
Enzo Cohen
(E)
Isabel Cuesta
(I)
Daniel Danis
(D)
Anne-Sophie Denommé-Pichon
(AS)
Yannis Duffourd
(Y)
Christian Gilissen
(C)
Mridul Johari
(M)
Steven Laurie
(S)
Shuang Li
(S)
Leslie Matalonga
(L)
Isabelle Nelson
(I)
Sophia Peters
(S)
Ida Paramonov
(I)
Sivakumar Prasanth
(S)
Peter Robinson
(P)
Karolis Sablauskas
(K)
Marco Savarese
(M)
Wouter Steyaert
(W)
Joeri K van der Velde
(JK)
Antonio Vitobello
(A)
Stefan Aretz
(S)
Gabriel Capella
(G)
Richarda M de Voer
(RM)
Gareth Evans
(G)
Jose Garcia Pelaez
(JG)
Elke Holinski-Feder
(E)
Nicoline Hoogerbrugge
(N)
Andreas Laner
(A)
Carla Oliveira
(C)
Andreas Rump
(A)
Evelin Schröck
(E)
Anna Katharina Sommer
(AK)
Verena Steinke-Lange
(V)
Iris Te Paske
(IT)
Marc Tischkowitz
(M)
Laura Valle
(L)
Siddharth Banka
(S)
Elisa Benetti
(E)
Giorgio Casari
(G)
Andrea Ciolfi
(A)
Jill Clayton-Smith
(J)
Bruno Dallapiccola
(B)
Elke de Boer
(E)
Anne-Sophie Denommé-Pichon
(AS)
Kornelia Ellwanger
(K)
Laurence Faivre
(L)
Holm Graessner
(H)
Tobias B Haack
(TB)
Anna Hammarsjö
(A)
Marketa Havlovicova
(M)
Alexander Hoischen
(A)
Anne Hugon
(A)
Adam Jackson
(A)
Tjitske Kleefstra
(T)
Anna Lindstrand
(A)
Estrella López-Martín
(E)
Milan Macek
(M)
Manuela Morleo
(M)
Vicenzo Nigro
(V)
Ann Nordgren
(A)
Maria Pettersson
(M)
Michele Pinelli
(M)
Simone Pizzi
(S)
Manuel Posada
(M)
Francesca Clementina Radio
(FC)
Alessandra Renieri
(A)
Caroline Rooryck
(C)
Lukas Ryba
(L)
Martin Schwarz
(M)
Marco Tartaglia
(M)
Christel Thauvin
(C)
Annalaura Torella
(A)
Aurélien Trimouille
(A)
Alain Verloes
(A)
Lisenka Vissers
(L)
Antonio Vitobello
(A)
Pavel Votypka
(P)
Klea Vyshka
(K)
Birte Zurek
(B)
Jonathan Baets
(J)
Danique Beijer
(D)
Gisèle Bonne
(G)
Enzo Cohen
(E)
Judith Cossins
(J)
Teresinha Evangelista
(T)
Alessandra Ferlini
(A)
Peter Hackman
(P)
Michael G Hanna
(MG)
Rita Horvath
(R)
Henry Houlden
(H)
Mridul Johari
(M)
Jarred Lau
(J)
Hanns Lochmüller
(H)
William L Macken
(WL)
Francesco Musacchia
(F)
Andres Nascimento
(A)
Daniel Natera-de Benito
(D)
Vincenzo Nigro
(V)
Giulio Piluso
(G)
Veronica Pini
(V)
Robert D S Pitceathly
(RDS)
Kiran Polavarapu
(K)
Pedro M Rodriguez Cruz
(PMR)
Anna Sarkozy
(A)
Marco Savarese
(M)
Rita Selvatici
(R)
Rachel Thompson
(R)
Bjarne Udd
(B)
Liedewei Van de Vondel
(L)
Jana Vandrovcova
(J)
Irina Zaharieva
(I)
Jonathan Baets
(J)
Peter Balicza
(P)
Patrick Chinnery
(P)
Alexandra Dürr
(A)
Tobias Haack
(T)
Holger Hengel
(H)
Henry Houlden
(H)
Erik-Jan Kamsteeg
(EJ)
Christoph Kamsteeg
(C)
Katja Lohmann
(K)
Alfons Macaya
(A)
Anna Marcé-Grau
(A)
Ales Maver
(A)
Judit Molnar
(J)
Alexander Münchau
(A)
Borut Peterlin
(B)
Olaf Riess
(O)
Ludger Schöls
(L)
Rebecca Schüle-Freyer
(R)
Giovanni Stevanin
(G)
Matthis Synofzik
(M)
Vincent Timmerman
(V)
Bart van de Warrenburg
(B)
Nienke van Os
(N)
Melanie Wayand
(M)
Carlo Wilke
(C)
Tobias B Haack
(TB)
Holm Graessner
(H)
Birte Zurek
(B)
Kornelia Ellwanger
(K)
Stephan Ossowski
(S)
German Demidov
(G)
Marc Sturm
(M)
Julia M Schulze-Hentrich
(JM)
Rebecca Schüle
(R)
Christoph Kessler
(C)
Melanie Wayand
(M)
Ludger Schöls
(L)
Holger Hengel
(H)
Peter Heutink
(P)
Han Brunner
(H)
Hans Scheffer
(H)
Nicoline Hoogerbrugge
(N)
Peter A C 't Hoen
(PAC)
Wouter Steyaert
(W)
Karolis Sablauskas
(K)
Erik-Jan Kamsteeg
(EJ)
Bart van de Warrenburg
(B)
Iris Te Paske
(I)
Erik Janssen
(E)
Marloes Steehouwer
(M)
Burcu Yaldiz
(B)
Anthony J Brookes
(AJ)
Colin Veal
(C)
Spencer Gibson
(S)
Marc Wadsley
(M)
Mehdi Mehtarizadeh
(M)
Umar Riaz
(U)
Greg Warren
(G)
Farid Yavari Dizjikan
(FY)
Thomas Shorter
(T)
Volker Straub
(V)
Chiara Marini Bettolo
(CM)
Sabine Specht
(S)
Jill Clayton-Smith
(J)
Siddharth Banka
(S)
Elizabeth Alexander
(E)
Adam Jackson
(A)
Laurence Faivre
(L)
Christel Thauvin
(C)
Yannis Duffourd
(Y)
Emilie Tisserant
(E)
Ange-Line Bruel
(AL)
Christine Peyron
(C)
Aurore Pélissier
(A)
Sergi Beltran
(S)
Ivo Glynne Gut
(IG)
Steven Laurie
(S)
Davide Piscia
(D)
Leslie Matalonga
(L)
Anastasios Papakonstantinou
(A)
Gemma Bullich
(G)
Alberto Corvo
(A)
Carles Garcia
(C)
Marcos Fernandez-Callejo
(M)
Carles Hernández
(C)
Daniel Picó
(D)
Ida Paramonov
(I)
Hanns Lochmüller
(H)
Gulcin Gumus
(G)
Virginie Bros-Facer
(V)
Ana Rath
(A)
Marc Hanauer
(M)
Annie Olry
(A)
David Lagorce
(D)
Svitlana Havrylenko
(S)
Katia Izem
(K)
Fanny Rigour
(F)
Alexandra Durr
(A)
Claire-Sophie Davoine
(CS)
Léna Guillot-Noel
(L)
Anna Heinzmann
(A)
Giulia Coarelli
(G)
Gisèle Bonne
(G)
Teresinha Evangelista
(T)
Valérie Allamand
(V)
Isabelle Nelson
(I)
Rabah Ben Yaou
(RB)
Corinne Metay
(C)
Bruno Eymard
(B)
Enzo Cohen
(E)
Antonio Atalaia
(A)
Tanya Stojkovic
(T)
Milan Macek
(M)
Marek Turnovec
(M)
Dana Thomasová
(D)
Radka Pourová Kremliková
(RP)
Vera Franková
(V)
Markéta Havlovicová
(M)
Vlastimil Kremlik
(V)
Helen Parkinson
(H)
Thomas Keane
(T)
Dylan Spalding
(D)
Alexander Senf
(A)
Daniel Danis
(D)
Glenn Robert
(G)
Alessia Costa
(A)
Christine Patch
(C)
Mike Hanna
(M)
Henry Houlden
(H)
Mary Reilly
(M)
Jana Vandrovcova
(J)
Francesco Muntoni
(F)
Anna Sarkozy
(A)
Vincent Timmerman
(V)
Jonathan Baets
(J)
Liedewei Van de Vondel
(L)
Danique Beijer
(D)
Peter de Jonghe
(P)
Sandro Banfi
(S)
Annalaura Torella
(A)
Alessandra Ferlini
(A)
Rita Selvatici
(R)
Rachele Rossi
(R)
Marcella Neri
(M)
Stefan Aretz
(S)
Isabel Spier
(I)
Sophia Peters
(S)
Carla Oliveira
(C)
Jose Garcia Pelaez
(JG)
Ana Rita Matos
(AR)
Celina São José
(CS)
Marta Ferreira
(M)
Irene Gullo
(I)
Susana Fernandes
(S)
Luzia Garrido
(L)
Pedro Ferreira
(P)
Fátima Carneiro
(F)
Morris A Swertz
(MA)
Lennart Johansson
(L)
Gerben van der Vries
(G)
Pieter B Neerincx
(PB)
Dieuwke Roelofs-Prins
(D)
Sebastian Köhler
(S)
Alison Metcalfe
(A)
Caroline Rooryck
(C)
Aurelien Trimouille
(A)
Raffaele Castello
(R)
Manuela Morleo
(M)
Alessandra Varavallo
(A)
Manuel Posada De la Paz
(MP)
Eva Bermejo Sánchez
(EB)
Estrella López Martín
(EL)
Beatriz Martínez Delgado
(BM)
F Javier Alonso García de la Rosa
(FJAG)
Francesca Clementina Radio
(FC)
Marco Tartaglia
(M)
Alessandra Renieri
(A)
Elisa Benetti
(E)
Peter Balicza
(P)
Maria Judit Molnar
(MJ)
Ales Maver
(A)
Borut Peterlin
(B)
Alexander Münchau
(A)
Katja Lohmann
(K)
Rebecca Herzog
(R)
Martje Pauly
(M)
Alfons Macaya
(A)
Anna Marcé-Grau
(A)
Andres Nascimiento Osorio
(AN)
Daniel Natera de Benito
(DN)
Hanns Lochmüller
(H)
Rachel Thompson
(R)
Kiran Polavarapu
(K)
David Beeson
(D)
Judith Cossins
(J)
Pedro M Rodriguez Cruz
(PMR)
Peter Hackman
(P)
Mridul Johari
(M)
Marco Savarese
(M)
Bjarne Udd
(B)
Rita Horvath
(R)
Gabriel Capella
(G)
Laura Valle
(L)
Elke Holinski-Feder
(E)
Andreas Laner
(A)
Verena Steinke-Lange
(V)
Evelin Schröck
(E)
Andreas Rump
(A)
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
Références
Genet Med. 2015 Jul;17(7):578-86
pubmed: 25356970
Genet Med. 2017 Feb;19(2):209-214
pubmed: 27441994
J Mol Diagn. 2020 Sep;22(9):1205-1215
pubmed: 32619640
Hum Mutat. 2019 Oct;40(10):1797-1812
pubmed: 31231902
Curr Protoc Bioinformatics. 2017 Jun 27;58:1.2.1-1.2.12
pubmed: 28654725
Genet Med. 2019 Jun;21(6):1267-1270
pubmed: 31015575
Am J Hum Genet. 2017 Feb 2;100(2):267-280
pubmed: 28132688
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Nucleic Acids Res. 2019 Jan 8;47(D1):D1018-D1027
pubmed: 30476213
Lancet. 2015 Apr 4;385(9975):1305-14
pubmed: 25529582
Eur J Hum Genet. 2020 Feb;28(2):165-173
pubmed: 31527858
Genome Med. 2019 Dec 17;11(1):83
pubmed: 31847883
Bioinformatics. 2019 Jun 1;35(11):1978-1980
pubmed: 30376034
Genet Med. 2018 Oct;20(10):1216-1223
pubmed: 29323667
Eur J Hum Genet. 2021 Sep;29(9):1348-1353
pubmed: 34075209
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Nucleic Acids Res. 2015 Jan;43(Database issue):D789-98
pubmed: 25428349
Eur J Hum Genet. 2021 Sep;29(9):1359-1368
pubmed: 34075211
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
J Mol Diagn. 2019 Jan;21(1):38-48
pubmed: 30577886
Nucleic Acids Res. 2016 Jan 4;44(D1):D862-8
pubmed: 26582918
Cell. 2019 Mar 21;177(1):32-37
pubmed: 30901545
Genet Med. 2020 Mar;22(3):633-639
pubmed: 31616070
N Engl J Med. 2019 Jun 20;380(25):2478-2480
pubmed: 31216405
Hum Mutat. 2016 Dec;37(12):1263-1271
pubmed: 27604516
Eur J Hum Genet. 2021 Sep;29(9):1332-1336
pubmed: 33972714
Nucleic Acids Res. 2020 Jan 8;48(D1):D913-D926
pubmed: 31642496
Eur J Hum Genet. 2021 Sep;29(9):1325-1331
pubmed: 34075208
Eur J Hum Genet. 2021 Sep;29(9):1354-1358
pubmed: 34075207
Genet Med. 2016 Nov;18(11):1090-1096
pubmed: 26938784