期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-019-10016-3
关键词
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资金
- Wellcome [WT095908, WT098051, WT108749/Z/15/Z, WT200990/Z/16/Z, HICF-1009-003]
- European Molecular Biology Laboratory
- European Union's Horizon 2020 research and innovation programme [634143]
- Department of Health [HICF-1009-003]
- Wellcome Sanger Institute [WT098051]
- Cambridge South REC [10/H0305/83]
- Republic of Ireland REC [GEN/284/12]
- National Institute for Health Research, through the Comprehensive Clinical Research Network
- Wellcome Trust [200990/Z/16/Z, WT091310]
- MRC Human Genetics Unit
- IGMM Translational Science Award
- Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6]
- Scottish Funding Council [HR03006]
- Medical Research Council UK
- Wellcome Trust (Wellcome Trust Strategic Award STratifying Resilience and Depression Longitudinally (STRADL)) [104036/Z/14/Z]
- MRC [MC_PC_U127527198, MC_UU_00007/1, MC_U127527198, G0600329, G0600237, MC_UU_00007/3] Funding Source: UKRI
We aimed to develop an efficient, flexible and scalable approach to diagnostic genome-wide sequence analysis of genetically heterogeneous clinical presentations. Here we present G2P (www.ebi.ac.uk/gene2phenotype) as an online system to establish, curate and distribute datasets for diagnostic variant filtering via association of allelic requirement and mutational consequence at a defined locus with phenotypic terms, confidence level and evidence links. An extension to Ensembl Variant Effect Predictor (VEP), VEP-G2P was used to filter both disease-associated and control whole exome sequence (WES) with Developmental Disorders G2P (G2P(DD); 2044 entries). VEP-G2P(DD) shows a sensitivity/precision of 97.3%/33% for de novo and 81.6%/22.7% for inherited pathogenic genotypes respectively. Many of the missing genotypes are likely false-positive pathogenic assignments. The expected number and discriminative features of background genotypes are defined using control WES. Using only human genetic data VEP-G2P performs well compared to other freely-available diagnostic systems and future phenotypic matching capabilities should further enhance performance.
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