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Abstract Engineers design for an inherently uncertain world. In the early stages of design processes, they commonly account for such uncertainty either by manually choosing a specific worst-case and multiplying uncertain parameters with safety factors or by using Monte Carlo simulations to estimate the probabilistic boundaries in which their design is feasible. The safety factors of this first practice are determined by industry and organizational standards, providing a limited account of uncertainty; the second practice is time intensive, requiring the development of separate testing infrastructure. In theory, robust optimization provides an alternative, allowing set-based conceptualizations of uncertainty to be represented during model development as optimizable design parameters. How these theoretical benefits translate to design practice has not previously been studied. In this work, we analyzed the present use of geometric programs as design models in the aerospace industry to determine the current state-of-the-art, then conducted a human-subjects experiment to investigate how various mathematical representations of uncertainty affect design space exploration. We found that robust optimization led to far more efficient explorations of possible designs with only small differences in an experimental participant’s understanding of their model. Specifically, the Pareto frontier of a typical participant using robust optimization left less performance “on the table” across various levels of risk than the very best frontiers of participants using industry-standard practices. 

Design of nucleic acid-based viral diagnostics typically follows heuristic rules and, to contend with viral variation, focuses on a genome’s conserved regions. A design process could, instead, directly optimize diagnostic effectiveness using a learned model of sensitivity for targets and their variants. Toward that goal, we screen 19,209 diagnostic–target pairs, concentrated on CRISPR-based diagnostics, and train a deep neural network to accurately predict diagnostic readout. We join this model with combinatorial optimization to maximize sensitivity over the full spectrum of a virus’s genomic variation. We introduce Activity-informed Design with All-inclusive Patrolling of Targets (ADAPT), a system for automated design, and use it to design diagnostics for 1,933 vertebrate-infecting viral species within 2 hours for most species and within 24 hours for all but three. We experimentally show that ADAPT’s designs are sensitive and specific to the lineage level and permit lower limits of detection, across a virus’s variation, than the outputs of standard design techniques. Our strategy could facilitate a proactive resource of assays for detecting pathogens.