Modeling and integrating interactions involving the CYP450 enzyme system in a multi-terminology server: Contribution to information extraction from a clinical data warehouse

•Cytochromic interactions has an impact on the therapeutic management of patients.•Detecting these drug interactions by informatic solutions will allow for better predictability in therapeutic response.•These enzymatic relations have been integrated in the HeTOP web server which is multi-terminological and cross-lingual.•These data allowed us to query the EDSaN CDW to high-light these cytochromic interactions. The cytochrome P450 (CYP450) enzyme system is involved in the metabolism of certain drugs and is responsible for most drug interactions. These interactions result in either an enzymatic inhibition or an enzymatic induction mechanism that has an impact on the therapeutic management of patients. Detecting these drug interactions will allow for better predictability in therapeutic response. Therefore, computerized solutions can represent a valuable help for clinicians in their tasks of detection. The objective of this study is to provide a structured data-source of interactions involving the CYP450 enzyme system. These interactions are aimed to be integrated in the cross-lingual multi-terminology server HeTOP (Health Terminologies and Ontologies Portal), to support the query processing of the clinical data warehouse (CDW) EDSaN (Entrepôt de Données de Santé Normand). A selection and curation of drug components (DCs) that share a relationship with the CYP450 system was performed from several international data sources. The DCs were linked according to the type of relationship which can be substrate, inhibitor, or inducer. These relationships were then integrated into the HeTOP server. To validate the CYP450 relationships, a semantic query was performed on the CDW, whose search engine is founded on HeTOP data (concepts, terms, and relations). A total of 776 DCs are associated by a new interaction relationship, integrated in HeTOP, by 14 enzymes. These are CYP450 1A2, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A7, 11B1,11B2 mitochondrial and P-glycoprotein, constituting a total of 2,088 relationships. A general modelling of cytochromic interactions was performed. From this model, 233,006 queries were processed in less than two hours, demonstrating the usefulness and performance of our CDW implementation. Moreover, they showed that in our university hospital, the concurrent prescription that could cause a cytochromic interaction is Bisoprolol with Amiodarone by enzymatic inhibition for 2,493 patients. The queries submitted to the CDW EDSaN allowed to h