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An open-loop approach to calculate noise-induced transitions
Farzaneh Maleki1, Attila Becskei1
1Biozentrum, Computational and systems biology, University of Basel, 4056 Basel, Switzerland.
Journal of Theoretical Biology
|December 21, 2016
Summary
This study introduces an open-loop approach to accurately predict cell fate transitions in bistable systems. This method simplifies calculations of mean first passage time (MFPT) and has practical applications in experimental data analysis.
Area of Science:
- Systems Biology
- Nonlinear Dynamics
- Stochastic Processes
Background:
- Bistability allows genetically identical cells to adopt distinct fates.
- Calculating noise-induced transitions in bistable systems is complex due to nonlinear dynamics and feedback loops.
Purpose of the Study:
- To develop a simplified theoretical framework for analyzing noise-induced transitions in bistable systems.
- To establish a method for predicting mean first passage time (MFPT) using an open-loop approach.
Main Methods:
- Opened multivariable feedback loops at the slowest variable to derive the open-loop function and output fluctuations.
- Reclosed the loop and employed the Fokker-Planck equation to calculate MFPT.
- Validated results against exact stochastic simulations.
Main Results:
- The open-loop approach accurately predicts MFPT, showing good agreement with simulations.
- External component interaction amplifies noise, shifting the open-loop function but maintaining predictive power for MFPT.
- Transition rates between cell fates increase with amplified extrinsic noise.
Conclusions:
- The stochastic open-loop approach simplifies theoretical analysis of bistable systems.
- Experimental measurement of open-loop output characteristics (mean, variance, timescale) allows direct prediction of MFPT.
- This method offers practical value for predicting system dynamics from experimental data.
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