Parameter identification in synthetic biological circuits using multi-objective optimization

摘要

Abstract: Synthetic biology exploits the of mathematical modeling of synthetic circuits both to predict the behavior of the designed synthetic devices, and to help on the selection of their biological components. The increasing complexity of the circuits being designed requires performing approximations and model reductions to get handy models. Parameter estimation in these models remains a challenging problem that has usually been addressed by optimizing the weighted combination of different prediction errors to obtain a single solution. The single-objective approach is inadequate to incorporate different kinds of experiments, and to identify parameters for an ensemble of biological circuit models. We present a methodology based on multi-objective optimization to perform parameter estimation that can fully harness to ensembles of local models for biological circuits. The methodology uses a global multi-objective evolutionary algorithm and a multi-criteria decision making strategy to select the most suitable solutions. Our approach finds an approximation to the Pareto optimal set of model parameters that correspond to each experimental scenario. Then, the Pareto set was clustered according to the experimental scenarios. This, in turn, allows to analyze the sensitivity of model parameters for different scenarios. Finally, we show the methodology applicability through the case study of a genetic incoherent feed-forward circuit, under different concentrations of the inducer input signal.