Implementing measurement error models with mechanistic mathematical models in a likelihood-based framework for estimation, identifiability analysis and prediction in the life sciences.

ABSTRACT

Throughout the life sciences, we routinely seek to interpret measurements and observations using parametrized mechanistic mathematical models. A fundamental and often overlooked choice in this approach involves relating the solution of a mathematical model with noisy and incomplete measurement data. This is often achieved by assuming that the data are noisy measurements of the solution of a deterministic mathematical model, and that measurement errors are additive and normally distributed. While this assumption of additive Gaussian noise is extremely common and simple to implement and interpret, it is often unjustified and can lead to poor parameter estimates and non-physical predictions. One way to overcome this challenge is to implement a different measurement error model. In this review, we demonstrate how to implement a range of measurement error models in a likelihood-based framework for estimation, identifiability analysis and prediction, called profile-wise analysis. This frequentist approach to uncertainty quantification for mechanistic models leverages the profile likelihood for targeting parameters and understanding their influence on predictions. Case studies, motivated by simple caricature models routinely used in systems biology and mathematical biology literature, illustrate how the same ideas apply to different types of mathematical models. Open-source Julia code to reproduce results is available on GitHub.