Drug-target network in myocardial infarction: A structural analysis

The identification of drug-target interactions is a crucial step in the drug-discovery process. It has been suggested that drug-target interactions are driven by drug-domain interactions. Based on the integration of two recently published datasets, i.e., Drug-target interactions in myocardial infarction (My-DTome) and drug-domain interaction network, this paper reports the association between drugs and protein domains in the context of myocardial infarction (MI). A MI drug-domain interaction network, My-DDome, was constructed. The functional similarity between domains based on their Gene Ontology (GO) annotations was estimated. The association between domains and therapeutic effects was investigated. Lists of GO annotations and Anatomical Therapeutic Chemical classification (ATC) codes highly enriched in My-DDome were identified. We show that drugs acting on blood and blood forming organs (ATC code B) and sensory organs (ATC code S) are significantly enriched in My-DDome (p <; 0.000001). Top enriched GO terms include GO:0003824 (catalytic activity), GO:0008152 (metabolic process) and GO:0030170 (pyridoxal phosphate binding). By incorporating protein domain information into My-DTome, more detailed insights into the interplay between drugs, their known targets and seemingly unrelated proteins are provided.