Machine learning workflow to enhance predictions of Adverse Drug Reactions (ADRs) through drug-gene interactions: application to drugs for cutaneous diseases

Abstract Adverse drug reactions (ADRs) pose critical public health issues, affecting over 6% of hospitalized patients. While knowledge of potential drug-drug interactions (DDI) is necessary to prevent ADR, the rapid pace of drug discovery makes it challenging to maintain a strong insight into DDIs....

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Autores principales: Kalpana Raja, Matthew Patrick, James T. Elder, Lam C. Tsoi
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/4ba7224201d24ca9b7d08693a91a8245
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Sumario:Abstract Adverse drug reactions (ADRs) pose critical public health issues, affecting over 6% of hospitalized patients. While knowledge of potential drug-drug interactions (DDI) is necessary to prevent ADR, the rapid pace of drug discovery makes it challenging to maintain a strong insight into DDIs. In this study, we present a novel literature-mining framework for enhancing the predictions of DDIs and ADR types by integrating drug-gene interactions (DGIs). The ADR types were adapted from a DDI corpus, including i) adverse effect; ii) effect at molecular level; iii) effect related to pharmacokinetics; and iv) DDIs without known ADRs. By using random forest classifier our approach achieves an F-score of 0.87 across the ADRs classification using only the DDI features. We then enhanced the performance of the classifier by including DGIs (F-score = 0.90), and applied the classification model trained with the DDI corpus to identify the drugs that might interact with the drugs for cutaneous diseases. We successfully predict previously known ADRs for drugs prescribed to cutaneous diseases, and are also able to identify promising new ADRs.