A Pareto approach to resolve the conflict between information gain and experimental costs: Multiple-criteria design of carbon labeling experiments

Science revolves around the best way of conducting an experiment to obtain insightful results. Experiments with maximal information content can be found by computational experimental design (ED) strategies that identify optimal conditions under which to perform the experiment. Several criteria have been proposed to measure the information content, each emphasizing different aspects of the design goal, i.e., reduction of uncertainty. Where experiments are complex or expensive, second sight is at the budget governing the achievable amount of information. In this context, the design objectives cost and information gain are often incommensurable, though dependent. By casting the ED task into a multiple-criteria optimization problem, a set of trade-off designs is derived that approximates the Pareto-frontier which is instrumental for exploring preferable designs. In this work, we present a computational methodology for multiple-criteria ED of information-rich experiments that accounts for virtually any set of design criteria. The methodology is implemented for the case of 13C metabolic flux analysis (MFA), which is arguably the most expensive type among the ‘omics’ technologies, featuring dozens of design parameters (tracer composition, analytical platform, measurement selection etc.). Supported by an innovative visualization scheme, we demonstrate with two realistic showcases that the use of multiple criteria reveals deep insights into the conflicting interplay between information carriers and cost factors that are not amendable to single-objective ED. For instance, tandem mass spectrometry turns out as best-in-class with respect to information gain, while it delivers this information quality cheaper than the other, routinely applied analytical technologies. Therewith, our Pareto approach to ED offers the investigator great flexibilities in the conception phase of a study to balance costs and benefits.Author summary: Designing experiments is obligatory in the biosciences to valorize their scientific outcome. When the experiments are expensive, unfortunately, in practice often the costs emerge to be showstoppers. In this situation the question arises: How to get the most out of the experiment for your invest in terms of time and money? We approach this question by formulating the design task as a multiple-criteria optimization problem. Its solution produces a set of Pareto-optimal design proposals that feature the trade-off between information gain, as measured by different metrics, and the costs. Then, exploration of the design proposals allows us to make the best decision on information-economic experiments under given circumstances. Implemented in the field of isotope-based metabolic flux analysis, practical application of the Pareto approach provides detailed insight into the tight interplay of plenty of information carriers and cost factors. Supported by an innovative tailored visual representation scheme, the investigator is enabled to explore the options before conducting the experiment. With a practical showcase at hand, our computational study highlights the benefits of incorporating multiple information criteria apart from the costs, balancing the shortcomings of conventional single-objective experimental design strategies.