A cluster-based cell-type deconvolution of spatial transcriptomic data

Spatial transcriptomics (ST) has emerged as an efficient technology for mapping gene expression within tissue sections, offering informative spatial context for gene activities. However, most current ST techniques suffer from low spatial resolution, where each spatial location often contains cells of various types. Deconvolution methods are used to resolve the cell mixture within the spots, but conventional approaches rely on spot-by-spot analyses, which are limited by low gene expression levels and disregard spatial relationships between spots, ultimately reducing performance. Here, we introduce DECLUST, a cluster-based deconvolution method to accurately estimate the cell-type composition in ST data. The method identifies spatial clusters of spots using both gene expression and spatial coordinates, hence preserving the spatial structure of the tissue. Deconvolution is subsequently performed on the aggregated gene expression of individual clusters, mitigating the challenges associated with low expression levels in individual spots. We evaluate DECLUST on simulated ST datasets from a human breast cancer tissue and two real ST datasets from human ovarian cancer and mouse brain. We compare DECLUST to current methods including CARD, GraphST, Cell2location, and Tangram. The results indicate that DECLUST not only maintains the spatial integrity of tissues but also outperforms existing methods in terms of robustness and accuracy. In conclusion, DECLUST provides an effective and reliable approach for identifying cell-type compositions in ST data.