Development of a human genetics-guided priority score for 19,365 genes and 399 drug indications.
Nat Genet
; 56(1): 51-59, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38172303
ABSTRACT
Studies have shown that drug targets with human genetic support are more likely to succeed in clinical trials. Hence, a tool integrating genetic evidence to prioritize drug target genes is beneficial for drug discovery. We built a genetic priority score (GPS) by integrating eight genetic features with drug indications from the Open Targets and SIDER databases. The top 0.83%, 0.28% and 0.19% of the GPS conferred a 5.3-, 9.9- and 11.0-fold increased effect of having an indication, respectively. In addition, we observed that targets in the top 0.28% of the score were 1.7-, 3.7- and 8.8-fold more likely to advance from phase I to phases II, III and IV, respectively. Complementary to the GPS, we incorporated the direction of genetic effect and drug mechanism into a directional version of the score called the GPS with direction of effect. We applied our method to 19,365 protein-coding genes and 399 drug indications and made all results available through a web portal.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacogenética
/
Genética Humana
Limite:
Humans
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos