中文摘要
本项目拟在前期基础上,以上市后清热解毒中药注射剂判断为IgE介导过敏反应为例,采用主动监测嵌套网络药理学网络分析、遗传流行病学GWAS分析、血液样本检测、复杂系统多维涌现等理论及方法,站在临床真实世界角度,进行上市后中药注射剂过敏反应探究。首先,构建药物组分与靶标蛋白之间的关系,寻找过敏网络靶标,采用网络分析及可视化软件,对网络进行拓扑分析及能量转换、信息传递分析,并实现路径优化与可视化,虚拟筛选IgE介导过敏反应分子机制并进行通路定位;进而,对IgE基因多态性与过敏易感性基于GWAS进行meta综合评价,并与主动监测得到的患者临床数据过敏反应特征和危险因素分析、血液样本检测结果相关联,映射到"过敏表征一基因一靶标一组分"网络,实现微观机制到宏观辨证论治的多维涌现,有利于明确临床前安全性研究方向,节约科研资源。
英文摘要
The project intends to research the IgE-mediated allergy mechanism of TCM injections based on the active surveillance nested with the methods such as network analysis of network pharmacology, GWAS analysis of genetic epidemiology, blood samples tested and the multidimensional emerge of complex systems from virtual network target prediction to the real world, et cetera. So, first solving the problem of the allergic mechanism in the real world effectiveness of clinical safety.Above all, constructing the relationship between the drug component and target protein and searching the network target based on the analysis of blood samples of the allergic patients and matched ones in the active surveillance which based on the pre-project. Furthermore, achieving the route optimization and visualization, virtual screening the molecular mechanisms of IgE-mediated allergy and realizing the channel positioning based on the network analyzer which does the topological analysis and the optimization Dijkstra and Force-directed layout of the Cytoscape which is the network analysis and visualization software. Subsequently, analyzing the gene polymorphisms and IgE allergy susceptibility based on GWAS analysis of genetic epidemiology. And then, mapping the allergic reaction characteristics and factors from the active surveillance in the real world to the "allergic characterize -gene -target-drug component" SOD network, achieving micro to macro emergence of multi-dimensional by MAS. Finally, the project aims to the direction of premarket safety in the laboratory research and to save the research resources and industry costs.
