To Sobol or not to Sobol? The effects of sampling schemes in systems biology applications.

Computational and mathematical models in biology rely heavily on the parameters that characterize them. However, robust estimates for their values are typically elusive and thus a large parameter space becomes necessary for model study, particularly to make translationally impactful predictions. Sampling schemes exploring parameter spaces for models are used for a variety of purposes in systems biology, including model calibration and sensitivity analysis. Typically, random sampling is used; however, when models have a high number of unknown parameters or the models are highly complex, computational cost becomes an important factor. This issue can be reduced through the use of efficient sampling schemes such as Latin hypercube sampling (LHS) and Sobol sequences. In this work, we compare and contrast three sampling schemes - random sampling, LHS, and Sobol sequences - for the purposes of performing both parameter sensitivity analysis and model calibration. In addition, we apply these analyses to different types of computational and mathematical models of varying complexity: a simple ODE model, a complex ODE model, and an agent-based model. In general, the sampling scheme had little effect when used for calibration efforts, but when applied to sensitivity analyses, Sobol sequences exhibited faster convergence. While the observed benefit to convergence is relatively small, Sobol sequences are computationally less expensive to compute than LHS samples and also have the benefit of being deterministic, which allows for better reproducibility of results.