[论文解读] Heat shock partially dissociates the overlapping modules of the yeast protein-protein interaction network

Ágoston Mihalik, Péter Csermely|arXiv (Cornell University)|May 15, 2011

Bioinformatics and Genomic Networks被引用 1

一句话总结

本研究揭示，热休克导致酿酒酵母蛋白质-蛋白质相互作用网络的全局组织出现部分解体，模块重叠和连接性降低，加权直径增加4.9倍。重组过程类似于层积云到积云的转变，关键热休克蛋白形成局部枢纽和残余连接，表明这是一种普遍存在的系统级应激适应机制。

ABSTRACT

Network analysis became a powerful tool in recent years. Heat shock is a well-characterized model of cellular dynamics. S. cerevisiae is an appropriate model organism, since both its protein-protein interaction network (interactome) and stress response at the gene expression level have been well characterized. However, the analysis of the reorganization of the yeast interactome during stress has not been investigated yet. We calculated the changes of the interaction-weights of the yeast interactome from the changes of mRNA expression levels upon heat shock. The major finding of our study is that heat shock induced a significant decrease in both the overlaps and connections of yeast interactome modules. In agreement with this the weighted diameter of the yeast interactome had a 4.9-fold increase in heat shock. Several key proteins of the heat shock response became centers of heat shock-induced local communities, as well as bridges providing a residual connection of modules after heat shock. The observed changes resemble to a stratus-cumulus type transition of the interactome structure, since the unstressed yeast interactome had a globally connected organization, similar to that of stratus clouds, whereas the heat shocked interactome had a multifocal organization, similar to that of cumulus clouds. Our results showed that heat shock induces a partial disintegration of the global organization of the yeast interactome. This change may be rather general occurring in many types of stresses. Moreover, other complex systems, such as single proteins, social networks and ecosystems may also decrease their inter-modular links, thus develop more compact modules, and display a partial disintegration of their global structure in the initial phase of crisis. Thus, our work may provide a model of a general, system-level adaptation mechanism to environmental changes.

研究动机与目标

• 研究酵母蛋白质-蛋白质相互作用网络（相互作用组）在热休克应激下的重组机制。
• 利用mRNA表达数据，分析相互作用组中模块重叠和连接性的变化。
• 确定应激期间相互作用组的结构重组是否反映了一种普遍存在的系统级适应机制。
• 探讨关键热休克反应蛋白在重组网络中作为枢纽和连接体的作用。

提出的方法

• 基于热休克期间mRNA表达变化，计算酵母相互作用组中相互作用权重的变化。
• 使用加权网络分析映射蛋白质-蛋白质相互作用，评估连接性和模块组织结构。
• 量化网络拓扑结构的变化，包括加权直径和模块重叠，以评估结构重组。
• 识别热休克网络中的关键枢纽蛋白，并分析其在模块间连接中的作用。
• 使用层积云和积云的视觉与结构类比，描述从全局连通到多焦点网络结构的转变。

实验结果

研究问题

• RQ1 热休克如何改变酵母相互作用组中功能模块之间的重叠和连接性？
• RQ2 热休克对酵母蛋白质-蛋白质相互作用网络的全局拓扑组织结构有何影响？
• RQ3 哪些蛋白质在重组网络中成为核心，它们在维持部分连接性方面发挥什么作用？
• RQ4 所观察到的网络重组是否类似于已知的结构转变，例如从层积云到积云的形态转变？

主要发现

• 热休克导致酵母相互作用组的加权直径增加4.9倍，表明发生了显著的结构重组。
• 热休克后，相互作用组中功能模块之间的重叠和连接性均显著降低。
• 关键热休克反应蛋白在局部社区中成为核心枢纽，并作为模块间的桥梁，维持了部分连接性。
• 未受胁迫的相互作用组呈现全局连通的、类似层积云的结构，而热休克后的相互作用组则呈现出多焦点的、类似积云的组织结构。
• 所观察到的重组表明全局网络结构出现部分解体，这可能代表了一种普遍存在的系统级应激适应机制。