Abstract
Network analysis became a powerful tool giving new insights to the understanding of cellular behavior. Heat shock, the archetype of stress responses, is a well-characterized and simple 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.
Highlights
In the last decade due to the advance of high-throughput technologies system level inquiries became widespread
The major finding of our study is that heat shock induced a marked decrease in the inter-community connections of the yeast interactome
The observed changes resembled 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
Summary
In the last decade due to the advance of high-throughput technologies system level inquiries became widespread. The network approach emerged as a versatile tool to assess the background of the regulation and changes of cellular functions. Analysis of protein-protein interaction (PPI) networks gives rich system level information to understand the functional organization of living cells [1,2,3,4,5,6]. In protein-protein interaction networks tight modules are corresponding to large protein complexes. More extensive, pervasively overlapping modules detected by recent methods, including ours, revealed a deeper insight to the multifunctionality of cellular proteins [7,8,9]. Despite of the widespread studies on network modules, the overlaps of interactome modules have not been studied yet in detail
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