Democratizing the spatial view: STAMP technology from an analytical perspective

Single-cell RNA sequencing (scRNA-seq) has transformed the profiling of cellular heterogeneity; however, tissue dissociation for scRNA-seq eliminates three critical classes of information that often define cell state: spatial organization, morphology, and protein localization. Spatial transcriptomics partially restores this context, yet many platforms are limited by cost, throughput, or experimental complexity. Single-cell transcriptomics analysis and multimodal profiling (STAMP) tackle these limitations by immobilizing cells or nuclei on a slide, enabling high-content imaging prior to molecular readout and consequently preserving each cell's visual characteristics alongside high-plex transcript and/or protein measurements. This mini review focuses on the downstream analytical workflow for STAMP datasets using Python, illustrating how standard single-cell methods can be applied to image-derived cell-by-feature matrices enriched with per-cell covariates. The pooled MIX sub-STAMP serves as a working example to illustrate practical steps for quality control, normalization, dimensionality reduction, clustering or label transfer, and program-level interpretation. Morpho-transcriptomic coupling is highlighted as an exploratory strategy that links inferred gene programs to image-derived morphology. Collectively, these analyses establish STAMP as a practical bridge between single-cell transcriptomics and quantitative cell phenotype, enabling interpretable state inference that can be validated by imaging-derived measurements.