The Th17 TRNs implicate phenotypes and putative regulators in Th17 cells. (A) TFs whose target genes are enriched in GWAS phenotype genes (FDR = 10%). (IBD) Inflammatory bowel disease; (chronic inflammatory diseases) chronic inflammatory diseases (ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis; pleiotropy). # GWAS, # TF, and # Overlap correspond to the number of genes associated with the phenotype, regulated by the TF in the Th17 TRN (KO + ChIP + ATAC), and the overlap between those two sets, respectively. Further details are contained in the Methods. (B) STAT3 and FOXB1 are central regulators of IBD genes. (Left) Each arrow corresponds to a single TF. Arrow source is TF's centrality (out degree, betweenness) in the full Th17 TRN, and arrowhead is TF centrality for the IBD subnetwork (in which target genes are limited to the 54 shared between the Th17 TRN and IBD GWAS set). STAT3 and FOXB1 (pink arrows) both show significant increase in degree centrality for IBD genes (FDR = 10%). (Right) The subnetwork connecting STAT3 and FOXB1 to their target genes in the IBD set. Node color indicates log2(fold-change) in Th17 48-h condition relative to other Th timepoints (red indicates increased; blue, decreased), whereas red/blue edges indicate positive/negative regulation. Solid edges have support in the ChIP + KO + ATAC prior, whereas dotted edges do not.
