A Cyber-Physical Platform for Model Calibration.

Synthetic biology has so far made limited use of mathematical models, mostly because their inference has been traditionally perceived as expensive and/or difficult. We have recently demonstrated how in silico simulations and in vitro/vivo experiments can be integrated to develop a cyber-physical platform that automates model calibration and leads to saving 60-80% of the effort. In this book chapter, we illustrate the protocol used to attain such results. By providing a comprehensive list of steps and pointing the reader to the code we use to operate our platform, we aim at providing synthetic biologists with an additional tool to accelerate the pace at which the field progresses toward applications.

Optimally Designed Model Selection for Synthetic Biology.

Modeling parts and circuits represents a significant roadblock to automating the Design-Build-Test-Learn cycle in synthetic biology. Once models are developed, discriminating among them requires informative data, computational resources, and skills that might not be readily available. The high cost entailed in model discrimination frequently leads to subjective choices on the selected structures and, in turn, to suboptimal models. Here, we outline frequentist and Bayesian approaches to model discrimination. We ranked three candidate models of a genetic toggle switch, which was adopted as a test case, according to the support from in vivo data. We show that, in each framework, efficient model discrimination can be achieved via optimally designed experiments. We offer a dynamical-systems interpretation of our optimization results and investigate their sensitivity to key parameters in the characterization of synthetic circuits. Our approach suggests that optimal experimental design is an effective strategy to discriminate between competing models of a gene regulatory network. Independent of the adopted framework, optimally designed perturbations exploit regions in the input space that maximally distinguish predictions from the competing models.