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Control of a bi-stable genetic system via parallelized reinforcement learning

Abstract:
Achieving real-time control of genetic systems is critical for improving the reliability, efficiency, and reproducibility of biological research and engineering. Yet the intrinsic stochasticity of these systems makes this goal difficult. Prior efforts have faced three recurring challenges: (a) predictive models of gene expression dynamics are often inaccurate or unavailable, (b) nonlinear dynamics and feedback in genetic circuits frequently lead to multi-stability, limiting the effectiveness of deterministic control strategies, and (c) slow biological response times make data collection for learning-based methods prohibitively time-consuming. Recent experimental advances now allow the parallel observation and manipulation of over a million individual cells, opening the door to model-free, data-driven control strategies. Here we investigate the use of Parallelized Q-Networks (PQN), a recently-developed reinforcement learning algorithm, to learn control policies for a simulated bistable gene regulatory network. We show that PQN can not only control this self-activating system more accurately than other model-free and model-based control methods previously used in the field, but also converges efficiently enough to be practical for experimental application. Our results suggest that parallelized experiments coupled with advances in reinforcement learning provide a viable path for real-time, model-free control of complex, multi-stable biological systems.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1109/cdc57313.2025.11312651

Authors

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Institution:
University of Oxford
Division:
MPLS
Department:
Engineering Science
Role:
Author
ORCID:
0000-0002-6587-840X
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Engineering Science
Oxford college:
Worcester College
Role:
Author
ORCID:
0000-0002-8374-6590


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Funder identifier:
https://ror.org/0439y7842
Grant:
EP/Y034791/1
EP/Y014073/1
Programme:
Engineering Biology CDT


Publisher:
IEEE
Host title:
2025 IEEE 64th Conference on Decision and Control (CDC)
Pages:
2898-2904
Publication date:
2025-12-12
Acceptance date:
2025-07-16
Event title:
64th IEEE Conference on Decision and Control (CDC 2025)
Event location:
Rio de Janeiro, Brazil
Event website:
https://cdc2025.ieeecss.org/
Event start date:
2025-12-10
Event end date:
2025-12-12
DOI:
EISSN:
2576-2370
ISSN:
0743-1546
EISBN:
9798331526276
ISBN:
9798331526283

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