Extended Robust Boolean Network of Budding Yeast Cell Cycle.

BACKGROUND

How to explore the dynamics of transition probabilities between phases of budding yeast cell cycle (BYCC) network based on the dynamics of protein activities that control this network? How to identify the robust structure of protein interactions of BYCC Boolean network (BN)? Budding yeast allows scientists to put experiments into effect in order to discover the intracellular cell cycle regulating structures which are well simulated by mathematical modeling.

METHODS

We extended an available deterministic BN of proteins responsible for the cell cycle to a Markov chain model containing apoptosis besides G1, S, G2, M, and stationary G1. Using genetic algorithm (GA), we estimated the kinetic parameters of the extended BN model so that the subsequent transition probabilities derived using Markov chain model of cell states as normal cell cycle becomes the maximum while the structure of chemical interactions of extended BN of cell cycle becomes more stable.

RESULTS

Using kinetic parameters optimized by GA, the probability of the subsequent transitions between cell cycle phases is maximized. The relative basin size of stationary G1 increased from 86% to 96.48% while the number of attractors decreased from 7 in the original model to 5 in the extended one. Hence, an increase in the robustness of the system has been achieved.

CONCLUSION

The structure of interacting proteins in cell cycle network affects its robustness and probabilities of transitions between different cell cycle phases. Markov chain and BN are good approaches to study the stability and dynamics of the cell cycle network.