Fig. 7: MASLD-associated metabolic modules revealed by Hotspot.
From: Spatially resolved multi-omics of human metabolic dysfunction-associated steatotic liver disease
a, Metabolites with significant spatial autocorrelation (1,528 metabolites, FDR < 0.01) were grouped into 20 Hotspot modules based on pairwise spatial correlation. b, Dot plot showing metabolic modules that align with disease conditions. Module expression scores were calculated using the Hotspot calculate_module_scores function, which centers metabolite expression based on a specified null model (depth-adjusted normal), smooths the value across a k-nearest neighbor (kNN) graph and then applies principal component analysis modeling using a single component. The resulting pixel loadings are reported as the module scores. c, Spatial distribution of Hotspot-identified module 5 in 12 representative tissue sections. d, Twenty-one metabolites from module 5 are presented as a heatmap, with columns representing the pixels within each disease status and the rows displaying metabolite annotations. e, Overlay of MSI data points and H&E image of Visium after alignment with STalign. f, Spatial distribution of Metabolic modules 5 and 13 (left) and gene topics 4 and 5 aligned using STalign (right). The zoomed-in graphs display PLA2G7 expression for three selected overlayed regions. g, Ranking of the top 100 genes for Topic4 based on gene weight to the topic, with metabolism-related genes emphasized. h, Stacked violin plot showing the expression of PLA2G7 across major cell types identified using scRNA-seq.
