Robustness guarantees for structured model reduction of dynamical systems with applications to biomolecular models

Abstract

Model reduction methods usually focus on the error performance analysis; however, in presence of uncertainties, it is important to analyze the robustness properties of the error in model reduction as well. This problem is particularly relevant for engineered biological systems that need to function in a largely unknown and uncertain environment. We give robustness guarantees for structured model reduction of linear and nonlinear dynamical systems under parametric uncertainties. We consider a model reduction problem where the states in the reduced model are a strict subset of the states of the full model, and the dynamics for all of the other states are collapsed to zero (similar to quasi-steady-state approximation). We show two approaches to compute a robustness guarantee metric for any such model reduction—a direct linear analysis method for linear dynamics and a sensitivity analysis based approach that also works for nonlinear dynamics. Using the robustness guarantees with an error metric and an input-output mapping metric, we propose an automated model reduction method to determine the best possible reduced model for a given detailed system model. We apply our method for the (1) design space exploration of a gene expression system that leads to a new mathematical model that accounts for the limited resources in the system and (2) model reduction of a population control circuit in bacterial cells.

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