Thor: a platform for cell-level investigation of spatial transcriptomics and histology.

Spatial transcriptomics integrates transcriptomics data with histological tissue images, offering deeper insights into cellular organization and molecular functions. However, existing computational platforms mainly focus on genomic analysis, leaving a gap in the seamless integration of genomic and image analysis. To address this, we introduce Thor, a comprehensive computational platform for multi-modal analysis of spatial transcriptomics and histological images. Thor utilizes an anti-shrinking Markov diffusion method to infer single-cell spatial transcriptomes from spot-level data, effectively integrating cell morphology with spatial transcriptomics. The platform features 10 modules designed for cell-level genomic and image analysis. Additionally, we present Mjolnir, a web-based tool for interactive tissue analysis using vivid gigapixel images that display information on histology, gene expression, pathway enrichment, and immune response. Thor's accuracy was validated through simulations and ISH, MERFISH, Xenium, and Stereo-seq datasets. To demonstrate its versatility, we applied Thor for joint genomic-histology analysis across various datasets. In in-house heart failure patient samples, Thor identified a regenerative signature in heart failure, with protein presence confirmed in blood vessels through immunofluorescence staining. Thor also revealed the layered structure of the mouse olfactory bulb, performed unbiased screening of breast cancer hallmarks, elucidated the heterogeneity of immune responses, and annotated fibrotic regions in multiple heart failure zones using a semi-supervised approach. Furthermore, Thor imputed high-resolution spatial transcriptomics data in an in-house bladder cancer sample sequenced using Visium HD, uncovering stronger spatial patterns that align more closely with histology. Bridging the gap between genomic and image analysis in spatial biology, Thor offers a powerful tool for comprehensive cellular and molecular analysis.