Quantitative Identification of Compound‐Dependent On‐Modules and Differential Allosteric Modules From Homologous Ischemic Networks
B Li, Jing Liu, YY Zhang, P.C. Wang, YN Yu, RX Kang, Wu Hl, Zhang Xx, Zheng Wang, Yueying Wang · CPT Pharmacometrics & Systems Pharmacology · 2016
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.