模块分析法:解密复杂疾病和药物作用机制的新策略

Module-based analysis: deciphering pathological and pharmacological mechanisms of complex diseases and multi-target drugs

大部分复杂疾病并不是由单个致病基因引起的,药物作用于疾病网络的多个靶点,产生协同效应,从而干预疾病的发生和发展。与作用于单个分子或通路的传统方法不同,高通量数据构建的疾病-药物靶点网络形象地展示了药物、靶点和疾病之间的复杂关系。但此类网络通常极为复杂,为了降低分析的复杂性,必须对大网络进行分解,识别出模块结构。该研究从模块的概念、结构和识别方法、疾病-药物模块识别的重要性及应用4个方面对模块分析法的框架进行了概述。模块分析法以一个全新的视角来解密药物干预复杂疾病的机制,为揭示多组分多靶点药物作用机制提供了新思路和新途径。

A complex disease is rarely a consequence of abnormality in a single gene. It is known that many drugs exhibit a therapeutic effect by acting on multiple targets,produce synergies to intervene the occurrence and development of diseases. Unlike the traditional methods which act on single molecule or pathway,this disease-drug target network constructed with high throughput data vividly showed the complex relationship between drugs,their targets and diseases. However,the networks are usually extremely complex. In order to reduce the complexity,it is necessary to deconstruct the network and identify module structures. In this study,framework of module analysis was summarized from four aspects： module concept,structure and identification methods,importance of disease-drug module identification,and its application. Module-based analysis provides a new perspective for deciphering the drug intervention mechanisms for complex diseases,and provides new ideas and pathways to reveal the mechanisms of multi-target and multi-component drugs.