人机协同贝叶斯优化框架,实现生物工艺中性能、约束与鲁棒性平衡。
A Human-in-the-Loop Bayesian Optimization Framework for Constraint-Aware Bioprocess Development

- 将高斯过程输出转化为多目标优化,通过帕累托前沿交互选优
- 同时优化性能、约束满足概率和输入扰动下的鲁棒性,8维细胞培养仿真验证
- 适合生物工艺开发人员,支持实验资源高效分配与决策迭代
本文扩展了帕累托前沿引导采样(PFGS)这一人机协同贝叶斯优化框架。通过将高斯过程(GP)代理模型的输出重新表述为多目标优化的目标,将生成的帕累托前沿交由领域专家交互选择候选方案,而非自动推荐单一结果。框架在两方面拓展:一是在多目标中引入满足输出规格限的后验概率作为显式目标,从GP后验分布解析计算;二是采用蒙特卡洛采样策略,估计用户定义输入扰动范围下的预期低置信性能,捕捉实际实施中的性能退化。最终的多维帕累托表示通过交互式仪表盘的二维投影,同步展现预测性能、模型不确定性、约束满足概率及输入鲁棒性的权衡关系,支持随代理模型改进与目标演化持续优化选择标准。该框架在八维分批补料中国仓鼠卵巢(CHO)细胞培养模拟器上展示,系统识别出高性能、可行性合规且对扰动具有韧性的工作条件,并证明专家定义的要求可作为合理停止准则,支撑实验资源的知情分配。
原文摘要 · Abstract (English)
This work presents an extension to Pareto Front Guided Sampling (PFGS), a Human-in-the-Loop (HitL) Bayesian Optimization (BO) framework in which Gaussian process (GP) surrogate-derived quantities are reformulated as objectives of a multi-objective optimization problem, and the resulting Pareto front is exposed to a domain expert for interactive candidate selection rather than returning a single automated recommendation. The framework is extended in two directions: constrained optimization is addressed by incorporating the posterior probability of satisfying output specification limits as an explicit Pareto objective, computed analytically from the GP posterior distribution; robust optimization is addressed by a Monte Carlo sampling strategy that estimates expected lower-confidence performance over a user-defined variability of input perturbations, capturing performance degradation under likely implementation deviations. The resulting multi-dimensional Pareto representation renders trade-offs between predicted performance, model uncertainty, probabilistic constraint satisfaction, and input robustness simultaneously visible through pairwise two-dimensional projections on an interactive dashboard, enabling selection criteria to be iteratively refined as the surrogate model improves and development objectives evolve. The framework is showcased on an eight-dimensional fed-batch Chinese Hamster Ovary (CHO) cell culture simulator demonstrating systematic identification of high-performing, feasibility-compliant, and perturbation-resilient operating conditions, and illustrating how expert-defined requirements provide a principled stopping criterion and support informed allocation of experimental resources.
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