Spatial Transcriptomics Microenvironment
Mapping high-resolution cell-type architecture and ligand-receptor signaling within intact tissue biopsies.
The Challenge
Single-cell sequencing requires tissue dissociation, which destroys critical spatial coordinates and cellular context. On the other hand, spatial transcriptomics platforms (like 10x Genomics Visium) capture multiple cells per spot, making it difficult to determine the exact cell-type distribution at cellular boundaries.
RASA's Technical Approach
RASA implemented an advanced spatial transcriptomics pipeline. We processed raw slide images and sequencing data using SpaceRanger. To resolve cell-type mixtures in individual spots, we applied Robust Cell Type Deconvolution (RCTD) using matching scRNA-seq references. We mapped tissue slice domains into spatial niches (tumor core, invasive border, normal tissue) and tracked ligand-receptor colocalization across adjacent spots using Giotto and Seurat's spatial module.
Results & Biological Insights
We analyzed and mapped over 50 tissue biopsies. The spatial deconvolution pipeline revealed a previously hidden immunosuppressive niche at the invasive border of breast tumors, characterized by colocalized Macrophage-T cell signaling. This spatial insight allowed our biopharma client to validate the mechanism of action of their leading antibody candidate and select patients for Phase I trials.