Qualitative and quantitative optimal experimental design for parameter identification

Abstract Mathematical models ensuring a highly predictive power are of inestimable value in systems biology. Their application ranges from investigations of basic processes in living organisms up to model based drug design in the field of pharmacology. For this purpose simulation results have to be consistent with the real process, i.e, suitable model parameters have to be identified minimizing the difference between the model outcome and measurement data. In this work graph based methods are used to figure out if conditions of parameter identifiability are fulfilled. In combination with network centralities, the structural representation of the underlying mathematical model provides a first guess of informative output configurations. As at least the most influential parameters should be identifiable and to reduce the complexity of the parameter identification process further a parameter ranking is done by Sobol ’ indices. The calculation of these indices goes along with a highly computational effort, hence monomial cubature rules are used as an efficient approach of numerical integration. All methods are demonstrated for a well known motif in signaling pathways, the MAP kinase cascade. 1