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8 days ago

Mechanism-Based Pharmacovigilance Over the Life-Sciences Linked-Open-Data Cloud


Adverse drug reactions (ADR) result in significant morbidity and mortality in patients, and a substantial proportion of these ADRs are caused by drug--drug interactions (DDIs). Pharmacovigilance methods are used to detect unanticipated DDIs and ADRs by mining Spontaneous Reporting Systems, such as the US FDA Adverse Event Reporting System (FAERS). However, these methods do not provide mechanistic explanations for the discovered drug--ADR associations in a systematic manner. In this paper, we present a systems pharmacology-based approach to perform mechanism-based pharmacovigilance. We integrate data and knowledge from four different sources using Semantic Web Technologies and Linked Data principles to generate a systems network. We present a network-based Apriori algorithm for association mining in FAERS reports. We evaluate our method against existing pharmacovigilance methods for three different validation sets. Our method has AUROC statistics of 0.7--0.8, similar to current methods, and event

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