Abstract Spatial genomic technologies characterize the relationship between the structural organization of cells and their cellular state. Despite the availability of various spatial transcriptomic and proteomic profiling platforms, these experiments remain costly and labor-intensive. Traditionally, tissue slicing for spatial sequencing involves parallel axis-aligned sections, often yielding redundant or correlated information. We propose structured batch experimental design , a method that improves the cost efficiency of spatial genomics experiments by profiling tissue slices that are maximally informative, while recognizing the destructive nature of the process. Applied to two spatial genomics studies—one to construct a spatially-resolved genomic atlas of a tissue and another to localize a region of interest in a tissue, such as a tumor—our approach collects more informative samples using fewer slices compared to traditional slicing strategies. This methodology offers a foundation for developing robust and cost-efficient design strategies, allowing spatial genomics studies to be deployed by smaller, resource-constrained labs.

Optimizing the design of spatial genomic studies