Figure 6.

Critical regulators of the four networks during T cell dysfunction

(A–D) Ranks for TFs in the four networks based on the integrated centrality measure. For each network, the top 10 TFs are labeled and colored by their regulatory patterns. The arrow marks the critical TF TSC22D3 present in W2, W3, and W4. (E) Venn diagram denoting overlap of targets of TSC22D3 in W2, W3, and W4. (F) Enriched GO terms of TSC22D3-regulated genes in each window. The color showing the −log₁₀ transformed p values of enrichment significance. (G) Violin plots showing expression levels of TSC22D3 in each cell state. Only cells with expression greater than 5 were used for visualization. (H–J) Boxplots displaying expression levels of TSC22D3 in pre-dysfunction and dysfunction states for hepatocellular carcinoma (H), melanoma (I), and colorectal cancer (J). The significance was evaluated by Wilcoxon test. Similarly, cells with low expression were not included for visualization, with a threshold of 5 for Smart-Seq2 datasets (GEO: GSE98638 and GSE108989) and 0.1 for the MARS-seq2 dataset (GEO: GSE123139). (K and L) Kaplan-Meier survival curves showing significant differences of survival probabilities for patient stratification based on TSC22D3 expression in GEO: GSE30219 (K) and GEO: GSE50081 (L).