Optimal Adaptive Testing for Epidemic Control: Combining Molecular and Serology Tests.

Epidemic interventions based on surveillance testing programs are a fundamental tool to control the first stages of new epidemics, yet they are costly, invasive and rely on scarce resources, limiting their applicability. To overcome these challenges, we investigate two optimal control problems: (i) how testing needs can be minimized while maintaining the number of infected individuals below a desired threshold, and (ii) how peak infections can be minimized given a typically scarce testing budget. We find that in both cases the optimal testing policy for the well-known Susceptible-Infected-Recovered (SIR) model is adaptive, with testing rates that depend on the epidemic state, and leads to significant cost savings compared to non-adaptive policies. By using the concept of observability, we then show that a central planner can estimate the required unknown epidemic state by complementing molecular tests, which are highly sensitive but have a short detectability window, with serology tests, which are less sensitive but can detect past infections.

Iterative experiment design guides the characterization of a light-inducible gene expression circuit.

Systems biology rests on the idea that biological complexity can be better unraveled through the interplay of modeling and experimentation. However, the success of this approach depends critically on the informativeness of the chosen experiments, which is usually unknown a priori. Here, we propose a systematic scheme based on iterations of optimal experiment design, flow cytometry experiments, and Bayesian parameter inference to guide the discovery process in the case of stochastic biochemical reaction networks. To illustrate the benefit of our methodology, we apply it to the characterization of an engineered light-inducible gene expression circuit in yeast and compare the performance of the resulting model with models identified from nonoptimal experiments. In particular, we compare the parameter posterior distributions and the precision to which the outcome of future experiments can be predicted. Moreover, we illustrate how the identified stochastic model can be used to determine light induction patterns that make either the average amount of protein or the variability in a population of cells follow a desired profile. Our results show that optimal experiment design allows one to derive models that are accurate enough to precisely predict and regulate the protein expression in heterogeneous cell populations over extended periods of time.