Figure 6.
WGCNA reveals a Th/Tc17 transcriptional program mediating breakthrough acute GVHD in NHP. (A) Topological overlap matrix plot with hierarchical clustering tree and the resulting gene modules from a weighted network of T-cell transcripts. (B) Eigengene adjacency heatmap showing module eigengene similarity to NHP clinical cohorts. (C) Visualization of gene coexpression network connections between the most connected genes in the orange module using Cytoscape. Shown are nodes and network connections with topological overlap above a threshold of 0.05. Mean expression fold-change values of breakthrough acute vs autologous cohorts for each gene is visualized using a false-color scale. (D) Visualization of gene coexpression network connections between the most connected genes in the black module using Cytoscape. Shown are nodes with network connections whose topological overlap is above a threshold of 0.05. Edges with network connections above the threshold of 0.07 are shown. Mean expression fold change values of breakthrough acute vs autologous cohorts for each gene are visualized using a false-color scale. (E) Flow cytometric analysis of PBMCs at the time of terminal analysis stimulated with PMA/ionomycin and measured for the production of IL17a. *P < .05 using an unpaired t test. (F) Pathway enrichment for genes in the black WGCNA module performed using DAVID.59 Shown are those terms with a P < .05 (corrected for multiple hypothesis testing using the Benjamini procedure). Significance values are displayed using a false-color scale and are given in units of −log10 of the corrected P value.