Optimal Design for Minimizing Uncertainty in Dynamic Equilibrium Systems

We further develop and utilize a previously described optimal design framework to investigate an oscillatory system of 16 states which simulates the circadian rhythm and intertwined positive and negative regulatory loops of Per, Cry, Bmal1, and Clock genes in mammals. We illustrate use of a subset selection methodology with experimental perturbations in order to increase and possibly maximize the amount of information gained from longitudinal data derived from such experiments. We demonstrate that optimizing experimental perturbations may substantially decrease uncertainty in estimating model parameters.