Control strategies for mitigating the effect for external perturbations on gene regulatory networks

Mathias Foo; Iulia Gherman; Katherine Denby; Declan Bates

doi:10.1016/j.ifacol.2017.08.2237

Control strategies for mitigating the effect for external perturbations on gene regulatory networks

Mathias Foo, Iulia Gherman, Katherine Denby, Declan Bates

Research output: Chapter in Book/Report/Conference proceeding › Conference proceeding › peer-review

2 Citations (Scopus)

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Abstract

External perturbations affecting gene regulatory networks, such as pathogen/virus attacks, can lead to adverse effects on the phenotype of the biological system. In this paper, we propose a systematic approach to mitigate the effect of such perturbations that can be implemented using the tools of synthetic biology. We use system identification techniques to build accurate models of an example gene regulatory network from time-series data, and proceed to identify the kernel architecture of the network, which is defined as the minimal set of interactions needed to reproduce the wild type temporal behaviour. The kernel architecture reveals four key pathways in the network which allow us to investigate a number of different mitigation strategies in the event of external perturbations. We show that while network reoptimisation can reduce the impact of perturbations, combining network rewiring with a synthetic feedback control loop allows the effect of the perturbation to be completely eliminated. The proposed approach highlights the potential of combining feedback control theory with synthetic biology for developing more resilient biological systems.

Original language	English
Title of host publication	IFAC World Congress
Publisher	IFAC-Papers OnLine
Pages	12647-12652
Number of pages	6
Volume	50
Edition	1
DOIs	https://doi.org/10.1016/j.ifacol.2017.08.2237
Publication status	Published - 9 Jul 2017
Event	The 20th World Congress of the International Federation of Automatic Control - Toulouse, France Duration: 9 Jul 2017 → 14 Jul 2017 https://www.ifac2017.org/

Conference

Conference	The 20th World Congress of the International Federation of Automatic Control
Abbreviated title	IFAC 2017
Country/Territory	France
City	Toulouse
Period	9/07/17 → 14/07/17
Internet address	https://www.ifac2017.org/

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in IFAC-Papers OnLine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in IFAC-Papers OnLine, Vol 50, (2017)] DOI: 10.1016/j.ifacol.2017.08.2237

© 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

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10.1016/j.ifacol.2017.08.2237

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Foo, M, Gherman, I, Denby, K & Bates, D 2017, Control strategies for mitigating the effect for external perturbations on gene regulatory networks. in IFAC World Congress. 1 edn, vol. 50, IFAC-Papers OnLine, pp. 12647-12652, The 20th World Congress of the International Federation of Automatic Control, Toulouse, France, 9/07/17. https://doi.org/10.1016/j.ifacol.2017.08.2237

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title = "Control strategies for mitigating the effect for external perturbations on gene regulatory networks",

abstract = "External perturbations affecting gene regulatory networks, such as pathogen/virus attacks, can lead to adverse effects on the phenotype of the biological system. In this paper, we propose a systematic approach to mitigate the effect of such perturbations that can be implemented using the tools of synthetic biology. We use system identification techniques to build accurate models of an example gene regulatory network from time-series data, and proceed to identify the kernel architecture of the network, which is defined as the minimal set of interactions needed to reproduce the wild type temporal behaviour. The kernel architecture reveals four key pathways in the network which allow us to investigate a number of different mitigation strategies in the event of external perturbations. We show that while network reoptimisation can reduce the impact of perturbations, combining network rewiring with a synthetic feedback control loop allows the effect of the perturbation to be completely eliminated. The proposed approach highlights the potential of combining feedback control theory with synthetic biology for developing more resilient biological systems.",

author = "Mathias Foo and Iulia Gherman and Katherine Denby and Declan Bates",

note = "NOTICE: this is the author{\textquoteright}s version of a work that was accepted for publication in IFAC-Papers OnLine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in IFAC-Papers OnLine, Vol 50, (2017)] DOI: 10.1016/j.ifacol.2017.08.2237 {\textcopyright} 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ ; The 20th World Congress of the International Federation of Automatic Control, IFAC 2017 ; Conference date: 09-07-2017 Through 14-07-2017",

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AU - Foo, Mathias

AU - Gherman, Iulia

AU - Denby, Katherine

AU - Bates, Declan

N1 - NOTICE: this is the author’s version of a work that was accepted for publication in IFAC-Papers OnLine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in IFAC-Papers OnLine, Vol 50, (2017)] DOI: 10.1016/j.ifacol.2017.08.2237 © 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2017/7/9

Y1 - 2017/7/9

N2 - External perturbations affecting gene regulatory networks, such as pathogen/virus attacks, can lead to adverse effects on the phenotype of the biological system. In this paper, we propose a systematic approach to mitigate the effect of such perturbations that can be implemented using the tools of synthetic biology. We use system identification techniques to build accurate models of an example gene regulatory network from time-series data, and proceed to identify the kernel architecture of the network, which is defined as the minimal set of interactions needed to reproduce the wild type temporal behaviour. The kernel architecture reveals four key pathways in the network which allow us to investigate a number of different mitigation strategies in the event of external perturbations. We show that while network reoptimisation can reduce the impact of perturbations, combining network rewiring with a synthetic feedback control loop allows the effect of the perturbation to be completely eliminated. The proposed approach highlights the potential of combining feedback control theory with synthetic biology for developing more resilient biological systems.

AB - External perturbations affecting gene regulatory networks, such as pathogen/virus attacks, can lead to adverse effects on the phenotype of the biological system. In this paper, we propose a systematic approach to mitigate the effect of such perturbations that can be implemented using the tools of synthetic biology. We use system identification techniques to build accurate models of an example gene regulatory network from time-series data, and proceed to identify the kernel architecture of the network, which is defined as the minimal set of interactions needed to reproduce the wild type temporal behaviour. The kernel architecture reveals four key pathways in the network which allow us to investigate a number of different mitigation strategies in the event of external perturbations. We show that while network reoptimisation can reduce the impact of perturbations, combining network rewiring with a synthetic feedback control loop allows the effect of the perturbation to be completely eliminated. The proposed approach highlights the potential of combining feedback control theory with synthetic biology for developing more resilient biological systems.

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DO - 10.1016/j.ifacol.2017.08.2237

M3 - Conference proceeding

VL - 50

SP - 12647

EP - 12652

BT - IFAC World Congress

PB - IFAC-Papers OnLine

T2 - The 20th World Congress of the International Federation of Automatic Control

Y2 - 9 July 2017 through 14 July 2017

ER -

Control strategies for mitigating the effect for external perturbations on gene regulatory networks

Abstract

Conference

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