Proof-of-concept study demonstrates bounded adaptive random local mutation calibrates sparse nonlinear bioprocess models, indicating that accurate fitting does not guarantee unique parameter recovery.
Sparse and unevenly informative observations can substantially limit parameter estimation in nonlinear bioprocess models. This proof-of-concept study investigates Bounded Adaptive Random Local Mutation (B-ARLM), a derivative-free algorithm for bounded parameter calibration, using a product-inhibited Andrews-type model of biological hydrogen production calibrated to six interval-average observations over 0–8 days. Andrews–P achieved the lowest in-sample calibration error among the three examined kinetic formulations, with a best-run NMSE of 1.29 × 10−3. Under a common budget of 2250 objective-function evaluations and 30 repeated runs, B-ARLM significantly outperformed the Fixed-EA ablation and the study-specific sCA-ES reference, while its terminal performance was not statistically distinguishable from canonical CMA-ES or jDE after Holm correction. Hyperparameter, broad-start, profile-NMSE, and observation-error sensitivity analyses were additionally performed. Broad-start optimization and two-dimensional profiling revealed widely separated near-optimal parameter vectors and pronounced parameter compensation, showing that accurate trajectory reconstruction does not imply unique kinetic-parameter recovery. The results support B-ARLM as a competitive bounded calibration strategy for the examined sparse-data problem while emphasizing the distinction between optimization performance, practical identifiability, and biological interpretation.
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Lyubenova et al. (2026) studied this question.
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