Motivation: It is widely accepted that cell signaling networks have been evolved to be robust against perturbations. To investigate the topological characteristics resulting in such robustness, we have examined large-scale signaling networks and found that a number of feedback loops are present mostly in coupled structures. In particular, the coupling was made in a coherent way implying that same types of feedback loops are interlinked together.
Results: We have investigated the role of such coherently coupled feedback loops through extensive Boolean network simulations and found that a high proportion of coherent couplings can enhance the robustness of a network against its state perturbations. Moreover, we found that the robustness achieved by coherently coupled feedback loops can be kept evolutionarily stable. All these results imply that the coherent coupling of feedback loops might be a design principle of cell signaling networks devised to achieve the robustness.