A novel paradigm for potential drug-targets discovery: quantifying relationships of enzymes and cascade interactions of neighboring biological processes to identify drug-targets

摘要: Target discovery is the most crucial step in a modern drug development. Our objective this study to propose novel paradigm for better discrimination of drug-targets and non-drug-targets with minimum disruptive side-effects under biological pathway context. We introduce metric, namely, “pathway closeness centrality”, each gene that jointly considers relationships its neighboring enzymes cross-talks processes, evaluate probability being drug-target. This metric could distinguish non-drug-targets. Genes lower centrality values are prone play marginal roles processes have less lethality risk, but appear tissue-specific expressions. Compared traditional metrics, our method outperforms degree, betweenness bridging human Analysis existing top 20 drugs indicates an appropriate index predict occurrence adverse pharmacological effects. Case studies prostate cancer type 2 diabetes mellitus indicate likely well from pathways. Thus, promising tool aid target identification discovery.