Boolean network model predicts cell cycle sequence of fission yeast.

Area of Science:

• Systems biology
• Computational biology
• Cell cycle regulation

Background:

• The cell cycle is a fundamental biological process crucial for cell division and organism development.
• Understanding the regulatory networks governing the cell cycle is key to deciphering cellular behavior and disease mechanisms.
• Existing models often rely on differential equations and numerous parameters, limiting insights into network topology's role.

Purpose of the Study:

• To construct a Boolean network model of the fission yeast (Schizosaccharomyces Pombe) cell-cycle regulatory network based solely on biochemical interaction topology.
• To simulate the model and compare its dynamics with known cell cycle progression in living cells.
• To investigate the robustness of cell cycle regulation and compare fission yeast dynamics with that of Saccharomyces cerevisiae.

Main Methods:

• Development of a Boolean network model using only the known biochemical interaction topology of the fission yeast cell-cycle regulatory network.
• Computer simulation of the Boolean model to reproduce the temporal sequence of regulatory protein activity during the cell cycle.
• Analysis of dynamical properties, including attractors and trajectories, and comparison with a similar model in Saccharomyces cerevisiae.

Main Results:

• The Boolean model successfully reproduced the known activity sequence of regulatory proteins in the fission yeast cell cycle without using any parameters.
• The model's dynamics demonstrated that the biological sequence is robustly implemented, with the G1 state as the dominant attractor and the cell cycle sequence as an attractive trajectory.
• A significant difference in circuitry and dynamics was observed when compared to a Saccharomyces cerevisiae model; fission yeast operates as an auto-excited system, unlike the damped system of S. cerevisiae.

Conclusions:

• Boolean network modeling, based purely on network topology, can faithfully represent complex biological dynamics like the cell cycle.
• The fission yeast cell-cycle network possesses inherent robustness, with its structure dictating a stable and predictable progression through cell cycle phases.
• Comparative analysis highlights distinct strategies employed by different yeast species in cell cycle regulation, suggesting evolutionary divergence in network architecture and dynamics.