Figure 6

Immune system and signal transduction GRNs are statistically conserved across unstimulated macrophage of five diverse murine strains. (a) The merger of five consequential GRNs predicts the core GRN (97,165 edges with 2159 nodes) conserved across five strains of mice. The core GRN has 57 TFs and 2102 genes. (b) Gene and pathway ontology of core GRN nodes by ClueGO revealed some of the significantly enriched ontology terms; protein metabolism, immune system, signal transduction, membrane trafficking, RNA metabolism, cell cycle, cellular responses to external stimuli, RHO GTPase effectors, and transcriptional regulation by TP53 (P ≤ 0.001) (Supplementary Figure S3). (c) The immune system ontology gene network is shared with other significant ontologies. Signal transduction and membrane trafficking have the most common genes involved with the immune system. (d) Core immune system GRN (1395 edges with 295 nodes). There are six TFs (Stat3, Jun, Stat6, Rela, Irf9, and Irf3) involved in core immune GRN. (e) Core immune genes are significantly enriched in Hub⁵⁰ (Hypergeometric enrichment test, P < 0.001) representing their importance in the robustness of the co-expression network. (f) The interactions of the core GRN immune system TFs in five strain-specific GRNs.