Extracting drug-enzyme relation from literature as evidence for drug drug interaction

Yaoyun Zhang, Heng-Yi Wu, Jingcheng Du, Jun Xu, Jingqi Wang, Cui Tao, Lang Li, Hua Xu

Information about drug-drug interactions (DDIs) is crucial for computational applications such as pharmacovigilance and drug repurposing. However, existing sources of DDIs have the problems of low coverage, low accuracy and low agreement. One common type of DDIs is related to the mechanism of drug metabolism: a DDI relation may be caused by different interactions (e.g., substrate, inhibit) between drugs and enzymes in the drug metabolism process. Thus, information from drug enzyme interactions (DEIs) serves as important supportive evidence for DDIs. Further, potential DDIs present implicitly could be detected by inference and reasoning based on DEIs. In this article, we propose a hybrid approach to combining machine learning algorithm with trigger words and syntactic patterns, for DEI relation extraction from biomedical literature. The extracted DEI relations are used for reasoning to infer potential DDI relations, based on a defined drug-enzyme ontology incorporating biological knowledge. Evaluation results demonstrate that the performance of DEI relation extraction is promising, with an F-measure of 84.97 % on the in vivo dataset and 65.58 % on the in vitro dataset. Further, the inferred DDIs achieved a precision of 83.19 % on the in vivo dataset and 70.94 % on the in vitro dataset, respectively. A further examination showed that the overlaps between our inferred DDIs and those present in DrugBank were 42.02 % on the in vivo dataset and 19.23 % on the in vitro dataset, respectively. This paper proposed an effective approach to extract DEI relations from biomedical literature. Potential DDIs not present in existing knowledge bases were then inferred based on the extracted DEIs, demonstrating the capability of the proposed approach to detect DDIs with scientific evidence for pharmacovigilance and drug repurposing applications.