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Main Authors: Faquir, Hamza, Pájaro, Manuel, Otero-Muras, Irene
Format: Preprint
Published: 2024
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Online Access:https://arxiv.org/abs/2409.11036
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author Faquir, Hamza
Pájaro, Manuel
Otero-Muras, Irene
author_facet Faquir, Hamza
Pájaro, Manuel
Otero-Muras, Irene
contents Engineering biology requires precise control of biomolecular circuits, and Cybergenetics is the field dedicated to achieving this goal. A significant challenge in developing controllers for cellular functions is designing systems that can effectively manage molecular noise. To address this, there has been increasing effort to develop model-based controllers for stochastic biomolecular systems, where a major difficulty lies in accurately solving the chemical master equation. In this work we develop a framework for optimal and Model Predictive Control of stochastic gene regulatory networks with three key advantageous features: high computational efficiency, the capacity to control the overall probability density function enabling the fine-tuning of the cell population to obtain complex shapes and behaviors (including bimodality and other emergent properties), and the capacity to handle high levels of intrinsic molecular noise. Our method exploits an efficient approximation of the Chemical Master Equation using Partial Integro-Differential Equations, which additionally enables the development of an effective adjoint-based optimization. We illustrate the performance of the methods presented through two relevant studies in Synthetic Biology: shaping bimodal cell populations and tracking moving target distributions via inducible gene regulatory circuits.
format Preprint
id arxiv_https___arxiv_org_abs_2409_11036
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle A computational framework for optimal and Model Predictive Control of stochastic gene regulatory networks
Faquir, Hamza
Pájaro, Manuel
Otero-Muras, Irene
Quantitative Methods
Engineering biology requires precise control of biomolecular circuits, and Cybergenetics is the field dedicated to achieving this goal. A significant challenge in developing controllers for cellular functions is designing systems that can effectively manage molecular noise. To address this, there has been increasing effort to develop model-based controllers for stochastic biomolecular systems, where a major difficulty lies in accurately solving the chemical master equation. In this work we develop a framework for optimal and Model Predictive Control of stochastic gene regulatory networks with three key advantageous features: high computational efficiency, the capacity to control the overall probability density function enabling the fine-tuning of the cell population to obtain complex shapes and behaviors (including bimodality and other emergent properties), and the capacity to handle high levels of intrinsic molecular noise. Our method exploits an efficient approximation of the Chemical Master Equation using Partial Integro-Differential Equations, which additionally enables the development of an effective adjoint-based optimization. We illustrate the performance of the methods presented through two relevant studies in Synthetic Biology: shaping bimodal cell populations and tracking moving target distributions via inducible gene regulatory circuits.
title A computational framework for optimal and Model Predictive Control of stochastic gene regulatory networks
topic Quantitative Methods
url https://arxiv.org/abs/2409.11036