Abstract
Spatial proteomic and transcriptomic technologies enable high-throughput phenotyping of cells in situ, enabling quantification of spatial relationships among diverse cell populations. However, the experimental design choice of which regions of a tissue will be imaged can greatly impact the interpretation of spatial quantifications. That is, spatial relationships identified in one region of interest may not be interpreted consistently across other regions. To address this challenge, we introduce Kontextual, a method that considers alternative frames of reference for contextualizing spatial relationships. These contexts may represent landmarks, spatial domains, or groups of functionally similar cells that are consistent across regions. By modeling spatial relationships between cells relative to these contexts, Kontextual produces robust spatial quantifications that are not confounded by the region selected. We demonstrate in spatial proteomics and transcriptomics datasets that modeling spatial relationships this way is biologically meaningful and can improve the prediction of patient prognosis in a classification setting.