A two-loop optimization strategy for multi-objective optimal experimental design

A new strategy of optimal experimental design (OED) is proposed for a kinetically controlled synthesis system by considering both observation design and input design. The observation design that combines sampling scheduling and measurement set selection is treated as a single optimization problem arranged in the inner loop, while the optimization of input intensity is calculated in the outer loop. This multi-objective dynamic optimization problem is solved via the integration of particle swarm algorithm (for the outer loop) and the interior-point method (for the inner loop). Numerical studies demonstrate the efficiency of this optimization strategy and show the effectiveness of this integrated OED in reducing parameter estimation uncertainties. In addition, process optimization of the case study enzyme reaction system is investigated with the aim to obtain maximum production rate by taking into account of the experimental cost

An Information-Theoretic Framework for Optimal Design: Analysis of Protocols for Estimating Soft Tissue Parameters in Biaxial Experiments

A new framework for optimal design based on the information-theoretic measures of mutual information, conditional mutual information and their combination is proposed. The framework is tested on the analysis of protocols—a combination of angles along which strain measurements can be acquired—in a biaxial experiment of soft tissues for the estimation of hyperelastic constitutive model parameters. The proposed framework considers the information gain about the parameters from the experiment as the key criterion to be maximised, which can be directly used for optimal design. Information gain is computed through k-nearest neighbour algorithms applied to the joint samples of the parameters and measurements produced by the forward and observation models. For biaxial experiments, the results show that low angles have a relatively low information content compared to high angles. The results also show that a smaller number of angles with suitably chosen combinations can result in higher information gains when compared to a larger number of angles which are poorly combined. Finally, it is shown that the proposed framework is consistent with classical approaches, particularly D-optimal design

An experimental design tool to optimize inference precision in data-driven mathematical models of bacterial infections in vivo.

The management of bacterial diseases calls for a detailed knowledge about the dynamic changes in host-bacteria interactions. Biological insights are gained by integrating experimental data with mechanistic mathematical models to infer experimentally unobservable quantities. This inter-disciplinary field would benefit from experiments with maximal information content yielding high-precision inference. Here, we present a computationally efficient tool for optimizing experimental design in terms of parameter inference in studies using isogenic-tagged strains. We study the effect of three experimental design factors: number of biological replicates, sampling timepoint selection and number of copies per tagged strain. We conduct a simulation study to establish the relationship between our optimality criterion and the size of parameter estimate confidence intervals, and showcase its application in a range of biological scenarios reflecting different dynamics patterns observed in experimental infections. We show that in low-variance systems with low killing and replication rates, predicting high-precision experimental designs is consistently achieved; higher replicate sizes and strategic timepoint selection yield more precise estimates. Finally, we address the question of resource allocation under constraints; given a fixed number of host animals and a constraint on total inoculum size per host, infections with fewer strains at higher copies per strain lead to higher-precision inference