arXiv:2511.22893eess.SYcs.AI2025-11中稿 · conference paper: …

用强化学习控制光遗传开关时间,实现更精细的基因表达调控。

Switching-time bioprocess control with pulse-width-modulated optogenetics

  • 用占空比作为连续代理变量,避免细网格二值决策变量。
  • 脉宽调制使基因表达响应更平滑,提升过程可控性。
  • 适合需要精准动态调控的合成生物学与生物制造场景。

生物技术可通过动态控制提升生产效率。光遗传学利用光作为外部输入调节基因表达,实现蛋白水平的精细调控,从而解锁代谢动态控制和细胞生长调节。传统方法依赖光强度驱动(信号幅度),但在剂量-反应关系陡峭时,调控能力受限于完全激活或完全抑制,缺乏中间状态调节。脉宽调制通过在强迫周期内交替全开/全关光照,平均响应更平滑,增强可控性。优化脉宽调制涉及具有二元输入的切换时间最优控制问题,若在细化控制网格上建模并施加单调约束,决策变量数量随控制网格分辨率和强迫周期数急剧增长。本文提出基于强化学习的替代解法:通过占空比参数化控制动作,该连续代理变量编码每个强迫周期内的开-关切换时间,既保持光照的固有二元特性,又避免细网格二值决策变量,显著降低计算复杂度。

原文摘要 · Abstract (English)

Biotechnology can benefit from dynamic control to improve production efficiency. In this context, optogenetics enables modulation of gene expression using light as an external input, allowing fine-tuning of protein levels to unlock dynamic metabolic control and regulation of cell growth. Optogenetic systems can be actuated by light intensity. However, relying solely on intensity-driven control (i.e., signal amplitude) may fail to properly tune optogenetic bioprocesses when the dose-response relationship (i.e., light intensity versus gene-expression strength) is steep. In these cases, tunability is effectively constrained to either fully active or fully repressed gene expression, with little intermediate regulation. Pulse-width modulation can alleviate this issue by alternating between fully ON and OFF light intensity within forcing periods, thereby smoothing the average response and enhancing process controllability. Optimizing pulse-width-modulated optogenetics entails a switching-time optimal control problem with a binary input over multiple forcing periods. While this can be formulated as a mixed-integer optimization problem on a refined control grid with monotonic input constraints, the number of decision variables can grow rapidly with increasing control-grid resolution within forcing periods and with the total number of forcing periods, complicating the task. Here, we propose an alternative solution based on reinforcement learning. We parametrize control actions via the duty cycle, a continuous proxy variable that encodes the ON-to-OFF switching time within each forcing period, thereby respecting the intrinsic binary nature of the light intensity while avoiding fine-grid binary decision variables.

光遗传学强化学习生物制造动态控制

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