Quantifying Dynamic Regulation in Metabolic Pathways with Nonparametric Flux Inference

Abstract

One of the central tasks in systems biology is to understand how cells regulate their metabolism. Hierarchical regulation analysis is a powerful tool to study this regulation at the metabolic, gene-expression, and signaling levels. It has been widely applied to study steady-state regulation, but analysis of the metabolic dynamics remains challenging because it is difficult to measure time-dependent metabolic flux. Here, we develop a nonparametric method that uses Gaussian processes to accurately infer the dynamics of a metabolic pathway based only on metabolite measurements; from this, we then go on to obtain a dynamical view of the hierarchical regulation processes invoked over time to control the activity in a pathway. Our approach allows us to use hierarchical regulation analysis in a dynamic setting but without the need for explicitly time-dependent flux measurements.