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    动态蛋白质网络的构建、分析及应用研究进展

    The Construction, Analysis, and Applications of Dynamic Protein-Protein Interaction Networks

    • 摘要: 蛋白质组学的快速发展,特别是高通量技术的发展产生了大量的蛋白质相互作用数据,为人们从更深层次理解蛋白质之间的相互作用及其在复杂疾病的作用机理提供了基础.一个生物体内所有的蛋白质与蛋白质之间的相互作用组成的网络称为蛋白质网络.传统的研究多是基于静态的蛋白质网络模型.然而,由于蛋白质自身表达的动态性及蛋白质间相互作用的动态性,真实的蛋白质网络会随着时间和条件不断变化,与疾病的发生和发展有关的蛋白质功能模块也与这种动态变化密切相关.因此,研究者已经把注意力从关注蛋白质网络的静态属性转移到动态属性上,提出了一系列的动态蛋白质网络的构建方法.在介绍静态蛋白质网络的基础上,分类讨论了动态蛋白质网络的构建方法,将现有的动态蛋白质网络的构建方法归纳为基于蛋白质表达动态性的方法、基于多状态下表达及相关性变化的方法和基于时空动态变化的方法这3类:第1类体现的是蛋白质自身表达随时间演化的动态性,第2类则表现为不同条件下蛋白质之间表达相关性的改变,第3类则体现了蛋白质及蛋白质相互作用在时间和空间上的动态变化.然后,对动态蛋白质网络的蛋白质节点和相关子网络进行了动态分析并详细介绍了动态蛋白质网络在复杂疾病中的一些主流应用,如蛋白质复合物识别、蛋白质功能预测、生物标志物识别、疾病基因预测等.最后,对动态蛋白质网络所面临的挑战与未来的研究方向进行了探讨.

       

      Abstract: The rapid development of proteomics and high-throughput technologies, has produced a large amount of protein-protein interaction (PPI) data, which provides a foundation for further understanding the interactions between proteins and the biomedical mechanism of complex diseases. In an organism, a protein-protein interaction network (PIN) consists of all the proteins and their interactions. Most of the traditional studies on PINs are based on static networks. However, due to the dynamics of protein expressions and the dynamics of PPIs, the real PINs change with time and conditions. Protein function modules related with the occurrence and development of diseases are also bound with this dynamic change. Researchers have shifted their attentions from the static properties to dynamic properties, and proposed a series of methods for the construction of dynamic PINs. This paper is to review the construction, analysis and applications of dynamic PINs. Firstly, the existing dynamic PIN construction methods are discussed in three categories: the methods based on dynamic protein expressions, the methods based on multi-state expression and correlation changes and the methods based on spatial-temporal dynamic changes. The first category embodies the protein dynamic expression varying with time; the second category reflects the changes in the expression-related relationship between proteins under different conditions; while the third category describes the dynamic of proteins and the interactions in time and space. Then, the dynamic analysis of the proteins and the related subnetworks of the dynamic PINs are reviewed. Furthermore,the main applications in the complex diseases of dynamic PINs are discussed in details, such as the identification of protein complexes/functional modules, the detection of biomarkers, and the prediction of disease genes, etc. Finally, the challenges and future research directions of dynamic PINs are discussed.

       

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