Control-based continuation: a new approach to prototype synthetic gene networks.
File(s)acssynbio.1c00632.pdf (2.9 MB)
Published version
Author(s)
de Cesare, Irene
Salzano, Davide
di Bernardo, Mario
Renson, Ludovic
Marucci, Lucia
Type
Journal Article
Abstract
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.
Date Issued
2022-06-21
Date Acceptance
2022-06-01
Citation
ACS Synthetic Biology, 2022, 11 (7), pp.2300-2313
ISSN
2161-5063
Publisher
American Chemical Society
Start Page
2300
End Page
2313
Journal / Book Title
ACS Synthetic Biology
Volume
11
Issue
7
Copyright Statement
© 2022 The Authors. Published by American Chemical Society. This work is published under CC BY 4.0 International licence.
License URL
Sponsor
Royal Academy of Engineering
Royal Academy Of Engineering
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35729740
Grant Number
RF1516/15/11
RF1516/15/11
Subjects
bifurcations
control-based continuation
synthetic biology
toggle switch
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2022-06-21