Reduction of quantitative systems pharmacology models using artificial neural networks

Quantitative systems pharmacology models are often highly complex and not amenable to further simulation and/or estimation analyses. Model-order reduction can be used to derive a mechanistically sound yet simpler model of the desired input–output relationship. In this study, we explore the use of artificial neural networks for approximating an input–output relationship within highly dimensional systems models. We illustrate this approach using a model of blood coagulation. The model consists of two components linked together through a highly dimensional discontinuous interface, which creates a difficulty for model reduction techniques. The proposed approach enables the development of an efficient approximation to complex models with the desired level of accuracy. The technique is applicable to a wide variety of models and provides substantial speed boost for use of such models in simulation and control purposes.