A Human-in-the-Loop Bayesian Optimization Framework for Constraint-Aware Bioprocess Development
Authors: Samuel Stricker, Claus Wirnsperger, Alessandro Butté, Laura Helleckes, Gonzalo Guillén Gosálbez, Antonio del Rio Chanona, Mehmet Mercangöz
Abstract
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.
Human-in-the-loop Bayesian optimization (HITL BO) methods utilize human expertise to improve the sample-efficiency of BO. Most HITL BO methods assume that a domain expert can quantify their knowledge, for instance by pinpointing query locations or specifying their prior beliefs about the location of the maximum as a probability distribution. However, since human expertise is often tacit and cannot be explicitly quantified, we consider a setting where domain knowledge of an expert is elicited via pairwise comparisons of designs. We interpret the expert's pairwise judgements as noisy evidence about the values of the observable objective function and develop a principled method for combining the information obtained via direct observations and pairwise queries. Specifically, we derive a cost-aware value-of-information acquisition function that balances direct observations against pairwise queries. The proposed method approaches the convex hull of the trajectories of the individual information sources: when pairwise queries are cheap it substantially improves sample-efficiency over observation-only BO, and when pairwise queries are costly or noisy, it recovers the performance of standard BO by relying on direct observations alone.
Expensive constrained optimization problems in real-world industry design often involve constraint thresholds that are difficult to determine in advance. Engineers may need to adjust constraint thresholds to explore different feasibility-performance trade-offs, requiring solutions under a wide range of threshold settings. However, existing constrained Bayesian optimization methods treat each threshold configuration independently, leading to repeated optimization and failing to exploit the shared relationship among continuously varying thresholds. To address this challenge, we propose constraint-bound agnostic Bayesian optimization (CBA-BO), a learning-based framework that learns a parametric constraint model mapping thresholds to optimal solutions. Once learned, CBA-BO directly predicts solutions for arbitrary unseen threshold configurations without additional optimization, with a one-step Bayesian optimization refinement further improving solution quality. Experiments on benchmark and engineering problems demonstrate that CBA-BO learns a transferable threshold-solution mapping, enabling efficient prediction and optimization for arbitrary threshold queries. An intent-guided constraint-bound recommendation mechanism is further developed to improve objective performance while satisfying user-specified constraint preferences.
We introduce BASIL, a user-friendly desktop application for process optimization. BASIL employs a Bayesian approach, incorporating special acquisition functions that can be used to solve both single and multi-objective optimization problems. It provides a graphical interface that enables users to input their experimental parameters, optimization objectives, and legacy data. This is then used to build surrogate models, which are coupled with acquisition functions to guide and optimize a process towards a desired objective. To facilitate model building, BASIL provides a variety of predefined surrogate model templates. BASIL can be used to optimize any arbitrary experiment or process with known, user-defined input variables, optimization objectives, and defined output.
Kelvin P. Idanwekhai, Valeriia Kaneva, Stefano Menegatti +1