Quantitative identification of compounds-dependent on-modules and differential allosteric modules from homologous ischemic networks

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 15co-expression 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 Z summary 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),and1.27%(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.