Computer Science Research Institute, University of Ulster, Newtownabbey, UK.
IEEE Trans Nanobioscience. 2013 Sep;12(3):182-8. doi: 10.1109/TNB.2013.2263556. Epub 2013 Aug 19.
It has been well recognized that the pace of the development of new drugs and therapeutic interventions lags far behind biological knowledge discovery. Network-based approaches have emerged as a promising alternative to accelerate the discovery of new safe and effective drugs. Based on the integration of several biological resources including 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 firstly constructed, followed by topological analysis and functional characterization of the network. The results show that My-DDome has a very clear modular structure, where drugs interacting with the same domain(s) within each module tend to have similar therapeutic effects. Moreover it has been found 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), indicating that by incorporating protein domain information into My-DTome, more detailed insights into the interplay between drugs, their known targets, and seemingly unrelated proteins can be revealed.
人们已经认识到，新药和治疗干预措施的发展速度远远落后于生物知识的发现。基于网络的方法已经成为加速发现新的安全有效的药物的一种有前途的替代方法。本文基于整合了几种生物资源，包括最近发表的两个数据集，即心肌梗死中的药物-靶标相互作用（My-DTome）和药物域相互作用网络，报告了在心肌梗死（MI）背景下药物与蛋白质域之间的关联。首先构建了心肌梗死药物-域相互作用网络 My-DDome，然后对网络进行拓扑分析和功能表征。结果表明，My-DDome 具有非常清晰的模块结构，其中在每个模块中与相同域（多个）相互作用的药物往往具有相似的治疗效果。此外，还发现作用于血液和造血器官（ATC 代码 B）和感觉器官（ATC 代码 S）的药物在 My-DDome 中显著富集（p < 0.000001），这表明通过将蛋白质域信息纳入 My-DTome，可以更详细地揭示药物、其已知靶标和看似无关的蛋白质之间的相互作用。
