Expert-guided multi-objective optimization: an efficient strategy for parameter estimation of biological systems with limited data.

Calibrating biological models is challenging due to high-dimensional parameter spaces and the limited availability of reliable experimental data. In this study, we propose a hybrid calibra- tion framework that integrates expert knowledge into a multi-objective optimization process using NSGA-II algorithm. Our approach combines hard constraints derived from biological measurements with soft constraints encoding qualitative domain expertise, such as expected curve shapes or event timing. This dual-constraint strategy guides the search toward biologi- cally plausible parameter sets while preserving flexibility and interpretability. We demonstrate the effectiveness of our method on a benchmark model of skin wound healing, comparing it to standard and unconstrained optimization strategies. Results show that incorporating expert guidance significantly improves the biological relevance of simulated dynamics and mitigates overfitting, especially in underdetermined or uncertain settings. The framework is flexible, it- erative, and generalizable, offering a principled way to leverage domain knowledge for model calibration in complex biological systems.