Robust optimal design of experiments for model discrimination using an interactive software tool.

Mathematical modeling of biochemical processes significantly contributes to a better understanding of biological functionality and underlying dynamic mechanisms. To support time consuming and costly lab experiments, kinetic reaction equations can be formulated as a set of ordinary differential equations, which in turn allows to simulate and compare hypothetical models in silico. To identify new experimental designs that are able to discriminate between investigated models, the approach used in this work solves a semi-infinite constrained nonlinear optimization problem using derivative based numerical algorithms. The method takes into account parameter variabilities such that new experimental designs are robust against parameter changes while maintaining the optimal potential to discriminate between hypothetical models. In this contribution we present a newly developed software tool that offers a convenient graphical user interface for model discrimination. We demonstrate the beneficial operation of the discrimination approach and the usefulness of the software tool by analyzing a realistic benchmark experiment from literature. New robust optimal designs that allow to discriminate between the investigated model hypotheses of the benchmark experiment are successfully calculated and yield promising results. The involved robustification approach provides maximally discriminating experiments for the worst parameter configurations, which can be used to estimate the meaningfulness of upcoming experiments. A major benefit of the graphical user interface is the ability to interactively investigate the model behavior and the clear arrangement of numerous variables. In addition to a brief theoretical overview of the discrimination method and the functionality of the software tool, the importance of robustness of experimental designs against parameter variability is demonstrated on a biochemical benchmark problem. The software is licensed under the GNU General Public License and freely available at http://sourceforge.net/projects/mdtgui/.