Fig. 5

Integrative analysis of scATAC-seq and scRNA-seq infers putative arthritic regulatory programs. A Heatmap showing the motif enrichment p-adjusted values of each SF subpopulation, for each disease state (WT, hTNFtg as indicated). Motif enrichment analysis was performed within the disease-specific marker peaks depicted in Fig. 4D (right panel). The color signifies the magnitude of the enrichment (−log10 (p-adjusted value), hypergeometric test). B Heatmap showing the motif deviation Z-scores of positive TF regulators across the SF subpopulations and samples (WT: wt-4w; hTNFtg/4weeks: tg-4w; and hTNFtg/8 weeks: tg-8w). TF gene expression is positively correlated with motif TF accessibility (Pearson correlation > 0.5, p-adjusted value < 0.05). C Expression dot plot of positive TF regulators shown in B. The color of the dots shows the intensity of expression, and the size denotes the percentage of cells expressing the gene in each cluster and condition. D Violin plots of regulon gene signature scores across SF subpopulations and samples (wt, hTNFtg/4 & 8 as indicated). Top panel: gene signature of 23 Ar-regulated genes with significantly increased expression and chromatin accessibility in sublining clusters. Peaks are enriched with the Ar motif. Bottom panel: gene signature of 181 Runx1-regulated genes with significantly increased expression and chromatin accessibility in intermediate and lining clusters. Peaks are enriched with the Runx1 motif. E Multimodal feature plots of Ar and Runx1 including scATAC gene activity (ATAC—gene activity scores), scRNA expression embedded to scATAC cells (ATAC—gene integration scores), and scATAC TF motif activity (ATAC—motif deviation scores). *NP1 full name: NP_0322962_LINE6262_NP_0322962_I_N2. *NP2 full name: NP_0322962_LINE1459_NP_0322962_I_N31