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

Abstract

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.

Network‐Wide Screen Identifies Variation of Novel Precise On‐Module Targets Using Conformational Modudaoism

“…Among them, the BA_8 module was conserved in all the 3 compound groups, and its functions involved regulation of apoptosis and cell death, transcription activator activity, MAPK, neurotrophin signaling pathway, etc. These functions were shown to be closely related to cerebral ischemia and also consistent with the findings from our previous studies . As for other CAMs in the three compound groups, the phosphorylation process was significantly enriched, which was a basically pathologic process in cerebral ischemia .…”

“…These functions were shown to be closely related to cerebral ischemia and also consistent with the findings from our previous studies. 18,42 As for other CAMs in the three compound groups, the phosphorylation process was significantly enriched, which was a basically pathologic process in cerebral ischemia. 42 These CAMs between different drugs reflect their common or synergetic pharmacological actions in treating a disease.…”

“…Based on the MDc value, more CAMs in BA, JA, and UA were identified than the Z summary ‐based method . Some modules were consistently defined as CAMs by both methods, such as the BA_8, JA_5, and UA_6 modules.…”

“…Based on the MDc value, more CAMs in BA, JA, and UA were identified than the Z summary -based method. 18 Some modules were consistently defined as CAMs by both methods, such as the BA_8, JA_5, and UA_6 modules. Among them, the BA_8 module was conserved in all the 3 compound groups, and its functions involved regulation of apoptosis and cell death, transcription activator activity, MAPK, neurotrophin signaling pathway, etc.…”

“…Our previous studies showed that baicalin (BA), jasminoidin (JA), and ursodeoxycholic acid (UA) had both similar and differential pharmacological mechanisms in treating cerebral ischemia at the pathway and network levels . A Z summary ‐based method was selected to identify the convergent or divergent modules, but the internal quality of modules was not considered . In this paper, based on the novel concept of MD, we proposed conserved MD (MDc) and varied MD (MDv) values to quantitatively discriminate the conserved and discrepant AMs of BA, JA, and UA in mice anti‐ischemic gene co‐expression networks, so as to further elucidate and compare their pharmacological mechanisms.…”