Show simple item record

dc.contributor.authorMatalonga, Leslie
dc.contributor.authorHernández-Ferrer, Carles
dc.contributor.authorPiscia, Davide
dc.contributor.authorSolve-RD SNV-indel working group
dc.contributor.authorSchüle, Rebecca
dc.contributor.authorSynofzik, Matthis
dc.contributor.authorTöpf, Ana
dc.contributor.authorVissers, Lisenka ELM
dc.contributor.authorde Voer, Richarda
dc.contributor.authorSolve-RD DITF-GENTURIS
dc.contributor.authorSolve-RD DITF-ITHACA
dc.contributor.authorSolve-RD DITF-euroNMD
dc.contributor.authorSolve-RD DITF-RND
dc.contributor.authorTonda, Raul
dc.contributor.authorLaurie, Steven
dc.contributor.authorFernandez-Callejo, Marcos
dc.contributor.authorPicó, Daniel
dc.contributor.authorGarcia-Linares, Carles
dc.contributor.authorPapakonstantinou, Anastasios
dc.contributor.authorCorvó, Alberto
dc.contributor.authorJoshi, Ricky
dc.contributor.authorDiez, Hector
dc.contributor.authorGut, Ivo
dc.contributor.authorHoischen, Alexander
dc.contributor.authorGraessner, Holm
dc.contributor.authorBeltran, Sergi
dc.contributor.authorSolve-RD Consortia
dc.date.accessioned2021-09-15T15:23:55Z
dc.date.available2021-09-15T15:23:55Z
dc.date.issued2021-09
dc.date.submitted2020-10-13
dc.identifier.issn1018-4813
dc.identifier.others41431-021-00852-7
dc.identifier.other852
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/328076
dc.descriptionFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 305444, 305444
dc.descriptionFunder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329
dc.descriptionFunder: Generalitat de Catalunya (Government of Catalonia); doi: https://doi.org/10.13039/501100002809
dc.descriptionFunder: EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj); doi: https://doi.org/10.13039/501100008530
dc.descriptionFunder: Instituto Nacional de Bioinformática ELIXIR Implementation Studies Centro de Excelencia Severo Ochoa
dc.descriptionFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)
dc.description.abstractReanalysis 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.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/692/699
dc.subject/631/208/2489/1512
dc.subject/631/114/2785
dc.subject/631/1647/2217
dc.subject/45/23
dc.subjectarticle
dc.titleSolving patients with rare diseases through programmatic reanalysis of genome-phenome data.
dc.typeArticle
dc.date.updated2021-09-15T15:23:54Z
prism.endingPage1347
prism.issueIdentifier9
prism.publicationNameEur J Hum Genet
prism.startingPage1337
prism.volume29
dc.identifier.doi10.17863/CAM.75533
dcterms.dateAccepted2021-02-26
rioxxterms.versionofrecord10.1038/s41431-021-00852-7
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidHernández-Ferrer, Carles [0000-0002-8029-7160]
dc.contributor.orcidSynofzik, Matthis [0000-0002-2280-7273]
dc.contributor.orcidVissers, Lisenka ELM [0000-0001-6470-5497]
dc.contributor.orcidde Voer, Richarda [0000-0002-8222-0343]
dc.contributor.orcidJoshi, Ricky [0000-0003-4463-0453]
dc.contributor.orcidGut, Ivo [0000-0001-7219-632X]
dc.contributor.orcidGraessner, Holm [0000-0001-9803-7183]
dc.contributor.orcidBeltran, Sergi [0000-0002-2810-3445]
dc.identifier.eissn1476-5438
pubs.funder-project-idEC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) (779257, 825575, 779257, 779257, 825575)
pubs.funder-project-idMinistry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) (PT13/0001/0044, PT17/0009/0019, PT13/0001/0044, PT17/0009/0019)
cam.issuedOnline2021-06-01


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record