Goles, E., Montalva, M., & Ruz, G. A. (2013). Deconstruction and Dynamical Robustness of Regulatory Networks: Application to the Yeast Cell Cycle Networks. Bull. Math. Biol., 75(6), 939–966.
Abstract: Analyzing all the deterministic dynamics of a Boolean regulatory network is a difficult problem since it grows exponentially with the number of nodes. In this paper, we present mathematical and computational tools for analyzing the complete deterministic dynamics of Boolean regulatory networks. For this, the notion of alliance is introduced, which is a subconfiguration of states that remains fixed regardless of the values of the other nodes. Also, equivalent classes are considered, which are sets of updating schedules which have the same dynamics. Using these techniques, we analyze two yeast cell cycle models. Results show the effectiveness of the proposed tools for analyzing update robustness as well as the discovery of new information related to the attractors of the yeast cell cycle models considering all the possible deterministic dynamics, which previously have only been studied considering the parallel updating scheme.
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Ruz, G. A., Goles, E., Montalva, M., & Fogel, G. B. (2014). Dynamical and topological robustness of the mammalian cell cycle network: A reverse engineering approach. Biosystems, 115, 23–32.
Abstract: A common gene regulatory network model is the threshold Boolean network, used for example to model the Arabidopsis thaliana floral morphogenesis network or the fission yeast cell cycle network. In this paper, we analyze a logical model of the mammalian cell cycle network and its threshold Boolean network equivalent. Firstly, the robustness of the network was explored with respect to update perturbations, in particular, what happened to the attractors for all the deterministic updating schemes. Results on the number of different limit cycles, limit cycle lengths, basin of attraction size, for all the deterministic updating schemes were obtained through mathematical and computational tools. Secondly, we analyzed the topology robustness of the network, by reconstructing synthetic networks that contained exactly the same attractors as the original model by means of a swarm intelligence approach. Our results indicate that networks may not be very robust given the great variety of limit cycles that a network can obtain depending on the updating scheme. In addition, we identified an omnipresent network with interactions that match with the original model as well as the discovery of new interactions. The techniques presented in this paper are general, and can be used to analyze other logical or threshold Boolean network models of gene regulatory networks. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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