Determination of critical network interactions: an augmented Boolean pseudo-dynamics approach.

Network theory has established that highly connected nodes in regulatory networks (hubs) show a strong correlation with criticality in network function. Although topological analysis is fully capable of identifying network hubs, it does not provide an objective method for ranking the importance of a particular node by relating its contribution to the overall network response. Towards this end, the authors have developed an augmented Boolean pseudo-dynamics approach to a priori determine the critical network interactions in biological interaction networks. The approach utilises network topology and dynamic state information to determine the set of active pathways. The active pathways are used in conjunction with the key cellular properties of efficiency and robustness, to rank the network interactions based on their importance in the sustenance of network function. To demonstrate the utility of the approach, the authors consider the well characterised guard cell signalling network in plant cells. An integrated analysis of the network revealed the critical mechanisms resulting in stomata closure in the presence and absence of abscisic acid, in excellent agreement with published results.