Timing robustness in the budding and fission yeast cell cycles

Area of Science:

• Systems biology
• Computational biology
• Cell cycle regulation

Background:

• Synchronous updates in Boolean models limit analysis of timing variations.
• Robustness to timing variations is essential for biological model accuracy under noisy conditions.

Purpose of the Study:

• To assess the speed independence of existing Boolean models of budding and fission yeast cell cycles.
• To investigate the impact of timing variations on biological model predictions and identify potential inaccuracies.

Main Methods:

• Construction of Boolean models from published mathematical models.
• Analysis using model-checking software to evaluate speed independence.
• In silico random mutations to assess robustness preservation.

Main Results:

• Cell cycle models are nearly, but not completely, speed-independent.
• Timing issues revealed model inaccuracies, which were corrected by biologically justified revisions.
• Random mutations rarely preserved speed independence in functional models.

Conclusions:

• Timing robustness is a significant feature in cell cycle models, likely driven by evolutionary selection.
• Timing robustness can guide hypothesis generation and identify areas for model refinement.
• Boolean models can be refined to improve accuracy and robustness to timing variations.