Realistic simulation of time-course measurements in systems biology.

Abstract

In systems biology, the analysis of complex nonlinear systems faces many methodological challenges. For the evaluation and comparison of the performances of novel and competing computational methods, one major bottleneck is the availability of realistic test problems. We present an approach for performing realistic simulation studies for analyses of time course data as they are typically measured in systems biology. Since the design of experiments in practice depends on the process of interest, our approach considers the size and the dynamics of the mathematical model which is intended to be used for the simulation study. To this end, we used 19 published systems biology models with experimental data and evaluated the relationship between model features (e.g., the size and the dynamics) and features of the measurements such as the number and type of observed quantities, the number and the selection of measurement times, and the magnitude of measurement errors. Based on these typical relationships, our novel approach enables suggestions of realistic simulation study designs in the systems biology context and the realistic generation of simulated data for any dynamic model. The approach is demonstrated on three models in detail and its performance is validated on nine models by comparing ODE integration, parameter optimization, and parameter identifiability. The presented approach enables more realistic and less biased benchmark studies and thereby constitutes an important tool for the development of novel methods for dynamic modeling.