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Toxicol Appl Pharmacol ; 343: 71-83, 2018 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-29454060

RESUMEN

The Adverse Outcome Pathway (AOP) framework describes the progression of a toxicity pathway from molecular perturbation to population-level outcome in a series of measurable, mechanistic responses. The controlled, computer-readable vocabulary that defines an AOP has the ability to, automatically and on a large scale, integrate AOP knowledge with publically available sources of biological high-throughput data and its derived associations. To support the discovery and development of putative (existing) and potential AOPs, we introduce the AOP-DB, an exploratory database resource that aggregates association relationships between genes and their related chemicals, diseases, pathways, species orthology information, ontologies, and gene interactions. These associations are mined from publically available annotation databases and are integrated with the AOP information centralized in the AOP-Wiki, allowing for the automatic characterization of both putative and potential AOPs in the context of multiple areas of biological information, referred to here as "biological entities". The AOP-DB acts as a hypothesis-generation tool for the expansion of putative AOPs, as well as the characterization of potential AOPs, through the creation of association networks across these biological entities. Finally, the AOP-DB provides a useful interface between the AOP framework and existing chemical screening and prioritization efforts by the US Environmental Protection Agency.


Asunto(s)
Rutas de Resultados Adversos/tendencias , Minería de Datos/métodos , Minería de Datos/tendencias , Bases de Datos Factuales/tendencias , Animales , Minería de Datos/estadística & datos numéricos , Bases de Datos Factuales/estadística & datos numéricos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/metabolismo , Redes Reguladoras de Genes/efectos de los fármacos , Redes Reguladoras de Genes/fisiología , Humanos , Medición de Riesgo/métodos , Medición de Riesgo/tendencias
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