用强化学习优化基因回路,自动应对实验不确定性。
Sequential Design of Genetic Circuits Under Uncertainty With Reinforcement Learning

- 基于RL策略与模拟器,动态设计实验以适应未知条件
- 训练一次即可实时响应,避免每次实验后复杂推断
- 适合处理分子噪声和跨实验室差异,适用于合成生物学
生物系统的设计受限于内在的生化反应随机性以及实验室间实验条件的差异。本文提出一种序列化框架,用于在上述两类不确定性下优化基因回路。通过结合微分方程或马尔可夫跳跃过程的模拟器与基于强化学习的策略方法,该方法能根据观测结果自适应地建议实验,同时考虑固有随机性。相较于以往依赖迭代实验-推断-优化循环的贝叶斯方法,本方法采用事前训练的摊销策略,覆盖多种可能的不确定参数分布,从而在设计过程中无需显式参数推断,实现即时响应。我们在异源基因表达模型和一个阻遏振荡器电路上验证了该框架,证明其能高效处理分子噪声和跨实验室变异性。
原文摘要 · Abstract (English)
The design of biological systems is hindered by uncertainty arising from both intrinsic stochasticity of biomolecular reactions and variability across laboratory or experimental conditions. In this work, we present a sequential framework to optimize genetic circuits under both forms of uncertainty. By employing simulator models based on differential equations or Markov jump processes alongside a reinforcement learning (RL) policy-based approach, our method suggests experiments that adapt to unknown laboratory conditions while accounting for inherent stochasticity. While previous Bayesian methods address uncertainty through iterative experiment-inference-optimization cycles, they typically require computationally expensive inference and optimization steps after each experimental round, leading to delays. To overcome this bottleneck, we propose an amortized approach trained up-front across a distribution of possible uncertain parameters. This strategy sidesteps the need for explicit parameter inference during the design cycle, enabling immediate, observation-based adaptation. We demonstrate our framework on models for heterologous gene expression and a repressilator circuit, showing that it efficiently handles both molecular noise and cross-laboratory variability.
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