title: Dynamical and topological robustness of the mammalian cell cycle network: a reverse engineering approach.
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.
authors.affiliation: Facultad de Ingeniería y Ciencias, Universidad Adolfo Ibáñez, Av. Diagonal Las Torres 2640, Santiago, Chile. Electronic address: gonzalo.ruz@uai.cl.
authors.forename: Gonzalo A
authors.initials: GA
authors.lastname: Ruz
authors.affiliation: Facultad de Ingeniería y Ciencias, Universidad Adolfo Ibáñez, Av. Diagonal Las Torres 2640, Santiago, Chile.
authors.forename: Eric
authors.initials: E
authors.lastname: Goles
authors.affiliation: Facultad de Ingeniería y Ciencias, Universidad Adolfo Ibáñez, Av. Diagonal Las Torres 2640, Santiago, Chile.
authors.forename: Marco
authors.initials: M
authors.lastname: Montalva
authors.affiliation: Natural Selection, Inc., 5910 Pacific Center Boulevard, Suite 315, San Diego, CA 92121, USA.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Fogel
mesh_terms: D000465:Algorithms; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D053263:Gene Regulatory Networks / Q000502:physiology*; D008322:Mammals / Q000502:physiology*; D008954:Models, Biological; D049490:Systems Biology / Q000379:methods
keywords: Bees algorithm; Boolean networks; Gene regulatory networks; Threshold networks; Topology robustness; Update robustness