title: Quantitative Determination of Flexible Pharmacological Mechanisms Based On Topological Variation in Mice Anti-Ischemic Modular Networks.
abstract: Targeting modules or signalings may open a new path to understanding the complex pharmacological mechanisms of reversing disease processes. However, determining how to quantify the structural alteration of these signalings or modules in pharmacological networks poses a great challenge towards realizing rational drug use in clinical medicine. Here, we explore a novel approach for dynamic comparative and quantitative analysis of the topological structural variation of modules in molecular networks, proposing the concept of allosteric modules (AMs). Based on the ischemic brain of mice, we optimize module distribution in different compound-dependent modular networks by using the minimum entropy criterion and then calculate the variation in similarity values of AMs under various conditions using a novel method of SimiNEF. The diverse pharmacological dynamic stereo-scrolls of AMs with functional gradient alteration, which consist of five types of AMs, may robustly deconstruct modular networks under the same ischemic conditions. The concept of AMs can not only integrate the responsive mechanisms of different compounds based on topological cascading variation but also obtain valuable structural information about disease and pharmacological networks beyond pathway analysis. We thereby provide a new systemic quantitative strategy for rationally determining pharmacological mechanisms of altered modular networks based on topological variation.
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.|Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Yin-Ying
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Yu
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Mathematical Sciences, Peking University, Beijing, China.
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Li
authors.affiliation: Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Yong-Yan
authors.initials: YY
authors.lastname: Wang
mesh_terms: D000495:Allosteric Site; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D002545:Brain Ischemia; D001931:Brain Mapping; D002626:Chemistry, Pharmaceutical / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D015233:Models, Statistical; D015398:Signal Transduction; D046888:Tissue Array Analysis