Predicting the clinical impact of human mutation with deep neural networks.
Nat Genet
; 50(8): 1161-1170, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-30038395
ABSTRACT
Millions of human genomes and exomes have been sequenced, but their clinical applications remain limited due to the difficulty of distinguishing disease-causing mutations from benign genetic variation. Here we demonstrate that common missense variants in other primate species are largely clinically benign in human, enabling pathogenic mutations to be systematically identified by the process of elimination. Using hundreds of thousands of common variants from population sequencing of six non-human primate species, we train a deep neural network that identifies pathogenic mutations in rare disease patients with 88% accuracy and enables the discovery of 14 new candidate genes in intellectual disability at genome-wide significance. Cataloging common variation from additional primate species would improve interpretation for millions of variants of uncertain significance, further advancing the clinical utility of human genome sequencing.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Genoma Humano
/
Mutação
/
Rede Nervosa
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos