Bioprocess mechanistic modeling is essential for advancing intelligent digital twin representation of biomanufacturing, yet challenges persist due to complex intracellular regulation, stochastic system behavior, and limited experimental data. This paper introduces a symbolic and statistical learning framework to identify key regulatory mechanisms and quantify model uncertainty. Bioprocess dynamics is formulated with stochastic differential equations characterizing intrinsic process variability, with a predefined set of candidate regulatory mechanisms constructed from biological knowledge. A Bayesian learning approach is developed, which is based on a joint learning of kinetic parameters and regulatory structure through a formulation of the mixture model. To enhance computational efficiency, a Metropolis-adjusted Langevin algorithm with adjoint sensitivity analysis is developed for posterior exploration. Compared to state-of-the-art Bayesian inference approaches, the proposed framework achieves improved sample efficiency and robust model selection. An empirical study demonstrates its ability to recover missing regulatory mechanisms and improve model fidelity under data-limited conditions.

Motivated by the pressing challenges in the digital twin development for biomanufacturing systems, we introduce an adjoint sensitivity analysis (SA) approach to expedite the learning of mechanistic model parameters. In this paper, we consider enzymatic stochastic reaction networks representing a multi-scale bioprocess mechanistic model that allows us to integrate disparate data from diverse production processes and leverage the information from existing macro-kinetic and genome-scale models. To support forward prediction and backward reasoning, we develop a convergent adjoint SA algorithm studying how the perturbations of model parameters and inputs (e.g., initial state) propagate through enzymatic reaction networks and impact on output trajectory predictions. This SA can provide a sample efficient and interpretable way to assess the sensitivities between inputs and outputs accounting for their causal dependencies. Our empirical study underscores the resilience of these sensitivities and illuminates a deeper comprehension of the regulatory mechanisms behind bioprocess through sensitivities.