SPARROW reveals microenvironment-zone-specific cell states in healthy and diseased tissues.

Spatially resolved transcriptomics technologies have advanced our understanding of cellular characteristics within tissue contexts. However, current analytical tools often treat cell-type inference and cellular neighborhood identification as separate and hard clustering processes, limiting comparability across scales and samples. SPARROW addresses these challenges by jointly learning latent embeddings and soft clusterings of cell types and cellular organization. It outperformed state-of-the-art methods in cell-type inference and microenvironment zone delineation and uncovered zone-specific cell states in human and mouse tissues that competing methods missed. By integrating spatially resolved transcriptomics and single-cell RNA sequencing (scRNA-seq) data in a shared latent space, SPARROW achieves single-cell spatial resolution and whole-transcriptome coverage, enabling the discovery of both established and unknown microenvironment zone-specific ligand-receptor interactions in the human tonsil. Overall, SPARROW is a computational framework that provides a comprehensive characterization of tissue features across scales, samples, and conditions.