Purpose(s)
Precision medicine has become a trend in medical treatment. In the field of drug metabolism, the crosstalk among multiple interaction types of Drug-metabolizing enzymes (DMEs) is key to facilitate the study of disease etiology and the optimization of clinical treatment. There are three major interaction types in an interactome: microbiome-DME interaction, xenobiotics-DME interaction and host protein-DME interaction.
Nowadays, various databases have been developed to provide DME-related data. However, no database has been designed to describe the key role of microbial DME in drug metabolism, and the interaction data of neither microbiome nor host protein, that alter drug metabolism by affecting DMEs, are provided in any available knowledge base. As the crosstalk among different interaction types is essential for drug metabolism and disposition, it is urgent to construct a database that comprehensively describes all three types of DME interactions.
Method(s)
A comprehensive literature review of all drugs (FDA approved, in clinical/preclinical) was performed to confirm their corresponding DMEs by searching the PubMed using keyword combinations.
The tissue/disease specific DME abundances data were collected as follows. Gene expression series records from the same microarray platform were gathered for data normalization, transformation, integration, perfect match correction, robust multiarray average and median polish. And the differential expression analysis was conducted.
A comprehensive literature review of all DMEs related interactome information by searching the PubMed using keyword combinations. And Data on differential methylation expression of DMEs in different diseases were obtained by integrating and calculating methylation expression microarray data.
Result(s)
A newly developed comprehensive database containing drug-metabolizing enzymes and their interactions, interactome of drug-metabolizing enzymes (INTEDE) was introduced.
Provided details of DMEs (1047 unique DMEs)
(1) the general information (2) the full list of drugs metabolized by this DME
(3) the tissue and disease specific-protein abundance of the DME
Provided three types of DME interaction data
(1) microbiome-DME interactions (MICBIOs) (2) host protein-DME interactions (HOSPPIs)
(3) xenobiotics-DME interactions (XEOTICs)
Conclusion(s)
INTEDE is unique in:
providing the largest number of DMEs that are manually curated and systematically confirmed based on their metabolizing drug(s)
covering the novel DME data of diverse microbes (parasitizing in different sites of human body) together with their metabolizing drug(s)
describing the comprehensive interactome data from three perspectives for both human and microbial DMEs
enabling the crosstalk analysis among various types of DME interaction