Optimally designed vs intuition-driven inputs: the study case of promoter activity modelling

Synthetic biology is an emerging engineering discipline that aims at synthesising logical circuits into cells to accomplish new functions. Despite a thriving community and some notable successes, the basic task of assembling predictable gene circuits is still a key challenge. Mathematical models are uniquely suited to help solve this issue. Yet in biology they are perceived as expensive and laborious to obtain because low-information experiments have often been used to infer model parameters. How much additional information can be gained using optimally designed experiments? To tackle this question we consider a building block in Synthetic Biology, an inducible promoter in yeast S. cerevisiae. Using in vivo data we re-fit a mathematical model for such a system; we then compare in silico the quality of the parameter estimates when model calibration is done using typical (e.g, step inputs) and optimally designed experiments. We find that Optimal Experimental Design leads to ~70% improvement in the predictive ability of the inferred models. We conclude providing suggestions on how optimally designed experiments can be implemented in vivo.