Fig. 3: The HLCA core conserves detailed biology and enables consensus-driven annotation.

a, A UMAP of the integrated HLCA, colored by level 1 annotation. b, Cluster label disagreement (label entropy) of Leiden 3 clusters of the HLCA. The HLCA was split into three parts (immune, epithelial and endothelial/stromal) for ease of visualization. Cells from every cluster are colored by label entropy. Clusters with less than 20% of cells annotated at level 3 are colored gray. c, Cell type label composition of the immune cluster with the most label disagreement (left), with original labels (middle left) and matching manual re-annotations (middle right). A zoom-in on the UMAP from b shows the final re-annotations (right). d, UMAPs of the immune, epithelial and endothelial/stromal parts of the HLCA core with cell annotations from the expert manual re-annotation. e, Percentage of cells originally labeled correctly, mislabeled or underlabeled (that is, only labeled at a coarser level) compared with final manual re-annotations. The percentages were calculated per manual annotation, as well as across all cells (right bar). f, UMAP of HLCA clusters annotated as rare epithelial cell types (that is, ionocytes, neuroendocrine cells and tuft cells). Final annotations, original labels and the study of origin are shown (top), as well as the expression of ionocyte marker FOXI1, tuft cell marker LRMP and neuroendocrine marker CALCA (bottom). g, Log-normalized expression of the migratory dendritic cell marker CCR7 in cells identified during re-annotation as migratory dendritic cells, versus other dendritic cells. AT, alveolar type; DC, dendritic cell; FB, fibroblast; Mph, macrophage; MT, metallothionein; SM, smooth muscle; SMG, submucosal gland; TB, terminal bronchiole.