Fig. 4: Predictions of key TFs involved in healthy to failed repair PT transition.

a Transcription factors (TFs) sorted by regulatory score, computed as the sum of predicted regulatory coefficients for healthy-FR PT DEGs multiplied by mean TF expression in PT (PCT, PST, KIM1 + PT) clusters. Negative scores indicate FR-promoting TFs—positive regulation of DEGs upregulated in FR PT or negative regulation of DEGs downregulated in FR-PT—and positive scores indicate H-promoting TFs—positive regulation of DEGs upregulated in H PT (PCT and PST) or negative regulation of DEGs downregulated in H PT. Similar TF rankings and scores replicated over n = 5 independent trials. b. Graph visualization of gene regulatory networks predicted by RENIN. TF node size represents centrality of TFs computed by PageRank, top 20 TFs are labeled. Source data are provided in the Source Data file. c Top 25 TFs ranked by betweenness. Source data are provided in the Source Data file. d Top 25 TFs ranked by PageRank. Source data are provided in the Source Data file. e r² calculated for RENIN- and Pando-predicted H-FR gene expression compared to target gene expression in an independent KPMP snRNA-seq dataset for genes that were successfully modeled by both methods. For shared genes, mean RENIN r² was .080 and mean Pando r² was .065. Source data are provided in the Source Data file. f r² calculated for RENIN- and CellOracle-predicted H-FR gene expression compared to target gene expression in an independent KPMP snRNA-seq dataset for genes that were successfully modeled by both methods. For shared genes, mean RENIN r² was .055 and mean CellOracle r² was .026. Source data are provided in the Source Data file. g Number of H-FR differentially expressed genes modeled by each method. Source data are provided in the Source Data file.