Figure 3.

Transcriptional responses in stimulated macrophages to perturbations in macrophage KDGs are predicted by the IBD networks. (a) Table values represent fold change in expression of the indicated KDG in stimulated versus unstimulated macrophages. The network image illustrates the LPS-induced gene expression changes (red increased expression; blue decreased expression; intensity indicates magnitude of fold change) in the CERTIFI KDG (diamond nodes) network neighborhoods. (b) The heat map represents the −log₁₀ P value for the enrichment of genes whose expression levels change in response to siRNA-mediated knockdown of the KDGs. The CERTIFI IBD network adjacent to the heat map is a representative example of genes that were upregulated (blue nodes) and downregulated (red nodes) in response to knockdown of the macrophage KDG TNFAIP3. The network-predicted TNFAIP3 signature was 1.84-fold enriched for genes in the TNFAIP3 macrophage knockdown signature (Fisher's exact test (FET) P = 0.003). (c) Subnetwork of cytokines whose protein levels change in response to siRNA knockdown of TNFAIP3 siRNA in macrophage. This subnetwork of differential protein cytokine expression contains TNFAIP3 as well as other KDGs including LAPTM5, DOCK2, and GBP5. The red node represents the macrophage KDG TNFAIP3; blue nodes represent cytokines significantly differentially expressed in response to siRNA knockdown of TNFAIP3; purple nodes represent KDGs.