Journal: Nature Communications
Article Title: FineST: contrastive learning integrates histology and spatial transcriptomics for nuclei-resolved ligand-receptor analysis
doi: 10.1038/s41467-026-70528-7
Figure Lengend Snippet: A , B Spatial plot of seven cell types estimated by cell2location (spot resolution) and FineST (single-cell resolution). A' , B' Zoon-in views of A and B . B'' Zoon-in view of the region marked in B' , where FineST increases resolution from 8 spots to 869 single cells. C Cell type composition from reference scRNA-seq and deconvolution at Visium spot and FineST single-cell levels. D Distribution and PCC of cell type proportions ( n = 7) for Visium spot (PCC = 0.24) and FineST single-cell (PCC = 0.64) resolutions vs reference scRNA-seq. E Pathologists identified 36 spots (of 1331) co-localized with tertiary lymphoid structure (TLS), important for antigen presentation and T cell activation. FineST's single-cell views validate TLS by T and B cell co-localization (see B'' ). F Three example spatially co-expressed LR pairs detected at FineST's single-cell resolution. G Visualization of PVR - TIGIT interaction among local single cells ( z -score FDR < 0.05). H Clustering of 633 significant LR pairs, from single-cell resolution, within selected ROI into three spatial patterns using SpatialDE. I Spatial co-localization of tumor and Treg cells, estimated by cell2location . J Spatially co-expressed LR pairs detected at FineST's single-cell resolution. Scatter plot of global Moran’s R and one-sided z -score p -values (orange: significant, FDR < 0.05, Benjamini-Hochberg correction), with examples highlighted. K Communication strength of CD70 - CD27 at single-cell resolution (color: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1-{p}_{{{{\rm{local}}}}{z}_{p}}$$\end{document} 1 − p local z p ; mean strength: 0.45, interacting cells: 5961, occupancy: 49.2%). L Detection of local CCC patterns by clustering significant LR pairs. Top: original spot resolution (332 pairs, SpatialDE); Middle: sub-spot resolution (957 pairs, SparseAEH) and Bottom: single-nucleus resolution (931 pairs, SparseAEH). M Dot plots of enriched pathways in Pattern 0 and Pattern 1 (from L , Bottom), 2-by-2 contingency tables for MHC-I and WNT. Statistical significance was assessed using a one-sided Fisher’s exact test; dot size indicates p -value. N Sankey plot of selected L-R-TF-TG communication pathways. For panels (D , K ), box plots show median (center), IQR (box), whiskers at 1.5 × IQR, and points for seven cell types; violin plots show density, median (white line), and IQR (thick bar). For panels ( A ), ( J , L ), source data are provided in the Source Data file.
Article Snippet: The raw and processed Visium spatial sequencing data of human hepatocellular carcinoma (HCC) tissues were downloaded from Mendeley Data under accession number skrx2fz79n [ https://data.mendeley.com/datasets/skrx2fz79n/1 ], while the cell type annotations and high-resolution HE-stained images were provided by the original corresponding author.
Techniques: Single Cell, Immunopeptidomics, Activation Assay
![A , B Spatial plot of seven cell types estimated by cell2location (spot resolution) and FineST (single-cell resolution). A' , B' Zoon-in views of A and B . B'' Zoon-in view of the region marked in B' , where FineST increases resolution from 8 spots to 869 single cells. C Cell type composition from reference scRNA-seq and deconvolution at Visium spot and FineST single-cell levels. D Distribution and PCC of cell type proportions ( n = 7) for Visium spot (PCC = 0.24) and FineST single-cell (PCC = 0.64) resolutions vs reference scRNA-seq. E Pathologists identified 36 spots (of 1331) co-localized with tertiary lymphoid structure (TLS), important for antigen presentation and T cell activation. FineST's single-cell views validate TLS by T and B cell co-localization (see B'' ). F Three example spatially co-expressed LR pairs detected at FineST's single-cell resolution. G Visualization of PVR - TIGIT interaction among local single cells ( z -score FDR < 0.05). H Clustering of 633 significant LR pairs, from single-cell resolution, within selected ROI into three spatial patterns using SpatialDE. I Spatial co-localization of tumor and Treg cells, estimated by cell2location . J Spatially co-expressed LR pairs detected at FineST's single-cell resolution. Scatter plot of global Moran’s R and one-sided z -score p -values (orange: significant, FDR < 0.05, Benjamini-Hochberg correction), with examples highlighted. K Communication strength of CD70 - CD27 at single-cell resolution (color: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1-{p}_{{{{\rm{local}}}}{z}_{p}}$$\end{document} 1 − p local z p ; mean strength: 0.45, interacting cells: 5961, occupancy: 49.2%). L Detection of local CCC patterns by clustering significant LR pairs. Top: original spot resolution (332 pairs, SpatialDE); Middle: sub-spot resolution (957 pairs, SparseAEH) and Bottom: single-nucleus resolution (931 pairs, SparseAEH). M Dot plots of enriched pathways in Pattern 0 and Pattern 1 (from L , Bottom), 2-by-2 contingency tables for MHC-I and WNT. Statistical significance was assessed using a one-sided Fisher’s exact test; dot size indicates p -value. N Sankey plot of selected L-R-TF-TG communication pathways. For panels (D , K ), box plots show median (center), IQR (box), whiskers at 1.5 × IQR, and points for seven cell types; violin plots show density, median (white line), and IQR (thick bar). For panels ( A ), ( J , L ), source data are provided in the Source Data file.](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_1544/pmc13201544/pmc13201544__41467_2026_70528_Fig4_HTML.jpg)
