Fig. 3: Expression gradient along the lobular axis and computational annotation of liver vein types.

a Enlarged view of a superimposed visualization of Sds, Cyp2f2 expression in the portal vein module, consisting of selected DEGs of cluster one (Supplementary Dataset 1), all with high values around the histological annotation of a portal vein (top). Expression of Glul, Cyp2e1 as representative marker-genes of the central vein module expression (Supplementary Dataset 1), consisting of DEGs of cluster 2 with high values around the histological annotation of a central vein (bottom). b Visualization of the average expression by distance to vein-type measured within 400 µm from the vein. The top row shows expression by distance of portal markers Sds, Cyp2f2, Hal, Hsd17b13 and Aldh1b1 to portal veins in blue and central veins in red, while the bottom row shows distances of central vein markers Glul, Oat, Slc1a2, Cyp2e1, and Cyp2a5 to portal veins in blue and central veins in red (top panel). Red and blue ribbons around the fitted line represent the standard error of the gene expression within spots along the distance to respective vein type. c Visualization of influence of distance to both vein types on expression by bivariate expression by distance plots (Methods). Gene expression values are depicted in a gradient from low (dark) to high values (light). The distance of each gene to central veins between 0 and 400 µm is represented on the x-axis. Simultaneously, distances to portal veins for the same distance are depicted on the y-axis for each gene. High values in the bottom right corner indicate gene expression is predominantly observed close to portal veins and far from central veins, while high values in the upper left corner indicate the reverse observation (below graphs). d Visual histological annotations (left) of central (red) and portal (blue) veins, including ambiguous visual annotations (green), compared with computational prediction, using the 10 marker genes from b (right). The classification of vein types is based on a weighted (by distance) average expression of the genes’ expression profiles in the neighborhood of each vein. In addition, the spatial expression data of spots neighboring uncertain morphological vascular annotations (green) can be used to predict periportal or pericentral vein types in the cases where visual annotations are ambiguous. e Expression by distance of portal—(top panel) and central—(bottom panel) markers. Probabilities for each class (central and portal) can be extracted from the logistic regression model, here given as P(central) or P(portal) (scale bar indicates 500 µm). Grey ribbons around the fitted line represent the standard error of the gene expression within spots along the distance to each of the depicted veins.