SpottedPy quantifies relationships between spatial transcriptomic hotspots and uncovers new environmental cues of epithelial-mesenchymal plasticity in cancer

Spatial transcriptomics is revolutionising the exploration of intratissue heterogeneity in cancer, yet capturing cellular niches and their spatial relationships remains challenging. We introduce SpottedPy, a Python package designed to identify tumour hotspots and map spatial interactions within the cancer ecosystem. Using SpottedPy, we examine epithelial-mesenchymal plasticity in breast cancer and highlight stable niches associated with angiogenic and hypoxic regions, shielded by CAFs and macrophages. Hybrid and mesenchymal hotspot distribution followed transformation gradients reflecting progressive immunosuppression. Our method offers flexibility to explore spatial relationships at different scales, from immediate neighbours to broader tissue modules, providing new insights into tumour microenvironment dynamics.