Quantitative Identification of Compound-Dependent On-Modules and Differential Allosteric Modules From Homologous Ischemic Networks.

Quantitative Identification of Compound-Dependent On-Modules and Differential Allosteric Modules From Homologous Ischemic Networks.
复制标题

从同源缺血网络中的化合物依赖性上模块和差异变构模块的定量鉴定。

DOI:
10.1002/psp4.12127
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发表时间:
2016-10
影响因子:
3.5
通讯作者:
Wang, Y Y
Wang, Y Y
中科院分区:
医学3区
文献类型:
--
作者:
Li, B;Liu, J;Zhang, Y Y;Wang, P Q;Yu, Y N;Kang, R X;Wu, H L;Zhang, X X;Wang, Z;Wang, Y Y

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基于模块的方法在解构生物网络方面取得了很大进展。然而,定量比较不同情况下模块(变构模块[AMs])的拓扑结构变化是一个很大的挑战。在全球抗缺血小鼠网络中,黄芩苷(BA)、茉莉素(JA)和熊去氧胆酸(UA)分别鉴定出23、42和15个共表达模块。然后,我们结合基于模块的一致性比率(MCR)和改进的Zsummary模块统计方法,在与车辆比较的基础上验证了模块上的12个BA, 22个JA和8个UA。两两比较的mcr分别为1.55% (BA vs JA)、1.45% (BA vs UA)和1.27% (JA vs UA)。在这些群体中鉴定出5个保守的变构模(CAMs)和17个独特的变构模(UAMs)。总之,以模块为中心的分析可以为我们提供一种独特的方法来理解模块化药理学时代与差异表型相关的多种药理学机制。
Module‐based methods have made much progress in deconstructing biological networks. However, it is a great challenge to quantitatively compare the topological structural variations of modules (allosteric modules [AMs]) under different situations. A total of 23, 42, and 15 coexpression modules were identified in baicalin (BA), jasminoidin (JA), and ursodeoxycholic acid (UA) in a global anti‐ischemic mice network, respectively. Then, we integrated the methods of module‐based consensus ratio (MCR) and modified Zsummary module statistic to validate 12 BA, 22 JA, and 8 UA on‐modules based on comparing with vehicle. The MCRs for pairwise comparisons were 1.55% (BA vs. JA), 1.45% (BA vs. UA), and 1.27% (JA vs. UA), respectively. Five conserved allosteric modules (CAMs) and 17 unique allosteric modules (UAMs) were identified among these groups. In conclusion, module‐centric analysis may provide us a unique approach to understand multiple pharmacological mechanisms associated with differential phenotypes in the era of modular pharmacology.