Robert G. Todd, Tomáš Helikar

It has been suggested that irreducible sets of states in Probabilistic Boolean Networks correspond to cellular phenotype. In this study, we identify such sets of states for each phase of the budding yeast cell cycle. We find that these "ergodic sets" underly the cyclin activity levels during each phase of the cell cycle. Our results compare to the observations made in several laboratory experiments as well as the results of differential equation models. Dynamical studies of this model: (i) indicate that under stochastic external signals the continuous oscillating waves of cyclin activity and the opposing waves of CKIs emerge from the logic of a Boolean-based regulatory network without the need for specific biochemical/kinetic parameters; (ii) suggest that the yeast cell cycle network is robust to the varying behavior of cell size (e.g., cell division under nitrogen deprived conditions); (iii) suggest the irreversibility of the Start signal is a function of logic of the G1 regulon, and changing the structure of the regulatory network can render start reversible.