Distilling Robust Design Principles of Biocircuits Using Mixed Integer Dynamic Optimization

A major challenge in model-based design of synthetic biochemical circuits is how to address uncertainty in the parameters. A circuit whose behavior is robust to variations in the parameters will have more chances to behave as predicted when implemented in practice, and also to function reliably in presence of fluctuations and noise. Here, we extend our recent work on automated-design based on mixed-integer multi-criteria dynamic optimization to take into account parametric uncertainty. We exploit the intensive sampling of the design space performed by a global optimization algorithm to obtain the robustness of the topologies without significant additional computational effort. Our procedure provides automatically topologies that best trade-off performance and robustness against parameter fluctuations. We illustrate our approach considering the automated design of gene circuits achieving adaptation.