Abstract
Synthetic biology aims at engineering synthetic circuits with pre-defined target functions. From a systems (model-based) perspective, the following problems are of central importance: (1) given the model of a biomolecular circuit, elucidate whether it is capable of a certain behavior/functionality; and (2) starting from a pre-defined required functionality and a library of biological parts, find the biomolecular circuit that, built as a combination of such parts, achieves the desired behavior. These two problems, framed, respectively, as nonlinear analysis and automated design problems, are tackled here by efficient optimization methods. We illustrate these methods with case studies considering the analysis and design of biocircuits capable of bistability (bistable switches). Bistability is of particular interest in the context of systems and synthetic biology because it endows cells with the capacity to make decisions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Dasika MS, Maranas CD (2008) OptCircuit: an optimization based method for computational design of genetic circuits. BMC Syst Biol 2:24
Pedersen M, Phillips A (2009) Towards programming languages for genetic engineering of living cells. J R Soc Interface 6:S437–S450
Marchisio MA, Stelling J (2011) Automatic design of digital synthetic gene circuits. PLOS Comp Biol 7:e1001083
Rodrigo G, Jaramillo A (2012) AutoBioCAD: full biodesign automation of genetic circuits. ACS Synth Biol 2:230–236
Marchisio MA (2014) Parts & Pools: a framework for modular design of synthetic gene circuits. Front Bioeng Biotechnol 2:42
Huynh L, Tagkopoulos I (2015) Fast and accurate circuit design automation through hierarchical model switching. ACS Synth Biol 4(8):890–897
Nielsen AAK, Der BS, Shin J et al (2016) Genetic circuit design automation. Science 352:aac7341
Otero-Muras I, Henriques D, Banga JR (2016) SYNBADm: a tool for optimization-based automated design of synthetic gene circuits. Bioinformatics 32(21):3360–3362
Watanabe L, Nguyen T, Zhang M et al (2019) iBioSim 3: a tool for model-based genetic circuit design. ACS Synth Biol 8(7):1560–1563
Pajaro M, Otero-Muras I, Vazquez C et al (2018) SELANSI: a toolbox for simulation of stochastic gene regulatory networks. Bioinformatics 34(5):893–895
Pajaro M, Otero-Muras I, Vazquez C et al (2019) Transient hysteresis and inherent stochasticity in gene regulatory networks. Nat Commun 10:4581
Kuznetsov YA (1998) Elements of applied bifurcation theory. Springer, New York
Gardner TS, Cantor CR, Collins JJ (2000) Construction of a genetic toggle switch in Escherichia coli. Nature 403:339–342
Gnügge R, Dharmarajan L, Lang M et al (2016) An orthogonal permease-inducer-repressor feedback loop shows bistability. ACS Synth Biol 403:339–342, 5(10):1098
Egea JA, Henriques D, Cokelaer T et al (2014) MEIGO: an open-source software suite based on metaheuristics for global optimization in systems biology and bioinformatics. BMC Bioinf 15:136
Yordanov P, Stelling J, Otero-Muras I (2020) BioSwitch: a tool for the detection of bistability and multi-steady state behaviour in signalling and gene regulatory networks. Bioinformatics. https://doi.org/10.1093/bioinformatics/btz746
Otero-Muras I, Banga JR (2018) Optimization-based prediction of fold bifurcations in nonlinear ODE models. IFAC-PapersOnLine 51(15):485–490
Govaerts W, Dhooge A, Kuznetsov Y et al (2003) Cl_MatCont: a continuation toolbox in Matlab. In: Proceedings of the 2003 ACM Symposium on Applied Computing, pp 161–166
Exler O, Schittkowski K (2007) A trust region SQP algorithm for mixed integer nonlinear programming. Optim Lett 1(3):269–280
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Otero-Muras, I., Banga, J.R. (2021). Synthetic Gene Circuit Analysis and Optimization. In: Marchisio, M.A. (eds) Computational Methods in Synthetic Biology. Methods in Molecular Biology, vol 2189. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0822-7_8
Download citation
DOI: https://doi.org/10.1007/978-1-0716-0822-7_8
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-0821-0
Online ISBN: 978-1-0716-0822-7
eBook Packages: Springer Protocols