Extended Data Fig. 12: Association of cell state scores with clinical phenotypes.
From: An atlas of healthy and injured cell states and niches in the human kidney
a. Embedding plots: grouping of patient-level expression profiles for the aTAL, aStr, Degen, and aPT genesets used for clinical outcome association (Supplementary Table 27) for snCv3 (Top) and scCv3 (Bottom). Barplots: the distribution of eGFR among the identified groups. b. Unadjusted Kaplan Meier curves by aStr (P = 0.001) and common aPT and aTAL (P = 0.03) state scores for composite of ESRD or 40% drop in eGFR from time of biopsy in Neptune adult patient cohort (see Supplementary Table 30). A score generated using 100 randomly selected genes failed to show any correlation (P = 0.52) with disease survival. c. Heatmap of causal variants (z-scores) that were enriched in SNARE2 cell-type specific accessible chromatin. Dots represent Z-scores > 2 (or P value < 0.05). Dotplots show averaged ESRRB binding site accessibility or gene expression (log values) and percent accessible or expressed. d. ESRRB subnetwork of TF connections to target genes generated using SNARE2 RNA and AC data, demonstrating a central role for ESRRB in regulating TAL marker genes. Inset shows the ESRRB motif. Boxes represent ESRRB target genes showing causal variant enrichment (c) within linked regulatory regions (AC peaks). e. Heatmap showing enrichment scores (scaled -log10(p values)) for the RNA expression (snCv3/scCv3) of gene sets associated with eQTL linked to kidney function or disease88,89 or associated with progression of acute to chronic injury90. f. Dot plots of averaged gene expression values (snCv3/scCv3) or TF binding site accessibilities (SNARE) and proportion expressed/accessible. Violin plots show gene expression scores for gene sets associated with aging (Tabula Muris Consortium48 and Takemon et al.69) or SASP (Ruscetti et al.70 or Basisty et al.71). g. Violin plots showing expression scores for gene sets shown in (f) for all non-immune subclasses. h. Bottom: Number of differentially expressed genes between AKI and CKD cases for each major cell type in snCv3 and scCv3 datasets. Top: enrichment of functional gene ontology terms for each major cell type. Colour indicates -log adjusted p-value (derived from GSEA and calculated based on permutation).
