Global sensitivity analysis of biological multi-scale models.

Mathematical models of biological systems need to both reflect and manage the inherent complexities of biological phenomena. Through their versatility and ability to capture behavior at multiple scales, multi-scale models offer a valuable approach. Due to the typically nonlinear and stochastic nature of multi-scale models as well as unknown parameter values, various types of uncertainty are present; thus, effective assessment and quantification of such uncertainty through sensitivity analysis is important. In this review, we discuss global sensitivity analysis in the context of multi-scale and multi-compartment models and highlight its value in model development and analysis. We present an overview of sensitivity analysis methods, approaches for extending such methods to a multi-scale setting, and examples of how sensitivity analysis can inform model reduction. Through schematics and references to past work, we aim to emphasize the advantages and usefulness of such techniques.