Laboratory of Cardiovascular Research, Public Research Centre for Health (CRP-Santé), 120 route d'Arlon, L-1150 Luxembourg, Luxembourg.
Sci Rep. 2011;1:52. doi: 10.1038/srep00052. Epub 2011 Aug 2.
The systems-level characterization of drug-target associations in myocardial infarction (MI) has not been reported to date. We report a computational approach that combines different sources of drug and protein interaction information to assemble the myocardial infarction drug-target interactome network (My-DTome). My-DTome comprises approved and other drugs interlinked in a single, highly-connected network with modular organization. We show that approved and other drugs may both be highly connected and represent network bottlenecks. This highlights influential roles for such drugs on seemingly unrelated targets and pathways via direct and indirect interactions. My-DTome modules are associated with relevant molecular processes and pathways. We find evidence that these modules may be regulated by microRNAs with potential therapeutic roles in MI. Different drugs can jointly impact a module. We provide systemic insights into cardiovascular effects of non-cardiovascular drugs. My-DTome provides the basis for an alternative approach to investigate new targets and multidrug treatment in MI.
迄今为止，尚未有研究对心肌梗死（MI）中的药物-靶点关联进行系统水平的描述。我们报告了一种计算方法，该方法结合了不同的药物和蛋白质相互作用信息来源，以构建心肌梗死药物-靶点相互作用网络（My-DTome）。My-DTome 由已批准的药物和其他药物相互连接在一个单一的、高度连接的网络中，具有模块化的组织。我们表明，已批准的药物和其他药物都可能具有高度的连接性，并代表网络瓶颈。这突出了这些药物通过直接和间接相互作用对看似不相关的靶点和途径的影响作用。My-DTome 模块与相关的分子过程和途径相关。我们发现证据表明，这些模块可能受 miRNA 调控，在 MI 中具有潜在的治疗作用。不同的药物可以共同影响一个模块。我们提供了系统的见解，了解非心血管药物对心血管的影响。My-DTome 为研究 MI 中的新靶点和多药物治疗提供了一种替代方法。
