期刊
ACS SYNTHETIC BIOLOGY
卷 -, 期 -, 页码 -出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.1c00632
关键词
control-based continuation; synthetic biology; bifurcations; toggle switch
资金
- EPSRC DTP Scholarship
- Medical Research Council [MR/N021444/1]
- Engineering and Physical Sciences Research Council [EP/R041695/1, EP/S01876X/1]
- European Union [766840]
- Royal Academy of Engineering [RF1516/15/11]
Control-Based Continuation (CBC) is a method for bifurcation analysis in physical experiments that overcomes uncertainty introduced through modeling and parameter estimation. By demonstrating its applicability in biochemical processes and cell growth and division simulations, CBC shows potential for accelerating the prototyping of synthetic gene regulatory networks.
Control-Based Continuation (CBC) is a general and systematic method to carry out the bifurcation analysis of physical experiments. CBC does not rely on a mathematical model and thus overcomes the uncertainty introduced when identifying bifurcation curves indirectly through modeling and parameter estimation. We demonstrate, in silico, CBC applicability to biochemical processes by tracking the equilibrium curve of a toggle switch, which includes additive process noise and exhibits bistability. We compare the results obtained when CBC uses a model-free and model-based control strategy and show that both can track stable and unstable solutions, revealing bistability. We then demonstrate CBC in conditions more representative of an in vivo experiment using an agent-based simulator describing cell growth and division, cell-to-cell variability, spatial distribution, and diffusion of chemicals. We further show how the identified curves can be used for parameter estimation and discuss how CBC can significantly accelerate the prototyping of synthetic gene regulatory networks.
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