Fig. 1: Outline of spatial transcriptomics processing and analysis pipeline.

In total, 45 lung tissue cores (3–5 mm) from unaffected and PF donors were processed on the Xenium Analyzer instrument on a combination of four TMAs of three to nine samples each and one additional replicate TMA with 17 additional samples and the inclusion of cell-bound stains. We quantified the expression of 343 genes at subcellular resolution using a custom panel. After filtering, we retained 299,018,086 high-quality transcripts for identifying transcript niches with GraphSAGE across all five TMAs. Of these, 210,370,118 transcripts on the original TMAs 1–4 were used to build the initial GraphSAGE model. After additional filtering, we annotated cell types for 1,630,319 segmented nuclei across the endothelial, epithelial, immune and mesenchymal lineages. An example sample shown is VUILD96LA (sarcoidosis diagnosis). The figure was created with BioRender.com.