Mapping the Tumor Microenvironment with Integrative Single-Cell RNA Sequencing and Spatial Proteomics: Uncovering Mechanisms of Disease and Therapeutic Resistance.

Understanding complex diseases such as cancer requires insight into both the intrinsic properties of individual cells and their interactions within the tumor microenvironment. Integrating single-cell RNA sequencing (scRNA-seq), which captures transcriptional states, with spatial proteomics, which provides spatially resolved protein expression data, offers a powerful opportunity to unravel disease mechanisms. In this protocol, we describe a framework that unifies scRNA-seq and spatial proteomics into a joint graph-based representation. This approach enables accurate prediction of disease pathologies and reveals critical cell-cell interactions that drive disease progression.