Table 5.
Functional Enrichment of Subnetworks of Top 20 KDs
| KD | Subnetwork Sources | Subnetwork Size | Over-Represented Pathway Categories |
|---|---|---|---|
| LUM | Brain | 45 | ECM; proteoglycans |
| COL1A1 | Liver | 73 | ECM; collagen formation |
| DUSP6 | Aorta | 253 | FRA pathway |
| DUSP6 | Artery | 50 | IL-6, IL-7 pathway; syndecan 4 pathway |
| DUSP6 | Cardiac muscle | 108 | AP1 pathway; IL-6, IL-7 pathway |
| DUSP6 | Smooth muscle | 17 | MAPK targets nuclear events mediated by map kinases; ERBB1 downstream pathway |
| DUSP6 | Vascular endothelium | 122 | IL-6, IL-7 pathway |
| HGD | Brain | 40 | PPAR signaling pathway; synthesis of bile acids and bile salts via 7alpha hydroxycholesterol |
| HGD | Muscle | 48 | Complement and coagulation cascades |
| MSN | Liver | 56 | Fcγ R-mediated; CXCR4 pathway |
| MSN | Vascular endothelium | 105 | Focal adhesion; integrin1 pathway |
| CXCL12 | Adipose | 47 | Adenylate cyclase activating and inhibitory pathway |
| CXCL12 | Liver | 30 | Intestinal immune network for IGA production; amino acid and oligopeptide SLC transporters |
| DUSP1 | Aorta | 179 | ECM |
| DUSP1 | Artery | 71 | Integrin1 pathway |
| DUSP1 | Smooth muscle | 63 | HIF1 pathway; FRA pathway |
| GBP2 | Blood | 20 | Interferon signaling |
| GBP2 | Kidney | 12 | Interferon signaling |
| MTMR11 | Liver | 80 | Integrin3 pathway |
| CCL18 | Aorta | 214 | Immune system |
| SLIT3 | Muscle | 28 | ECM |
| GBP1 | Adipose | 25 | Interferon signaling |
| GBP1 | Blood | 18 | Interferon signaling |
| GBP1 | Vascular endothelium | 92 | Interferon signaling |
| F2 | Adipose | 49 | Complement and coagulation cascades; AMI pathway |
| F2 | Muscle | 47 | Complement and coagulation cascades; intrinsic pathway |
| COL4A2 | Muscle | 28 | Collagens |
| COL4A2 | PPI | 19 | ECM; platelet amyloid precursor protein pathway |
| LOXL2 | Liver | 28 | Collagen formation; NCAM1 interactions |
| CXCL10 | Liver | 46 | Chemokine signaling pathway |
| ANXA3 | Liver | 49 | Matrisome associated; ECM regulators |
| SLC2A3 | Aorta | 190 | ECM; P53 downstream pathway |
| SHC1 | PPI | 118 | ERBB signaling pathway; focal adhesion |
| STAT3 | PPI | 102 | JAK-STAT signaling pathway; pathways in cancer |
Fisher exact test was performed for the enrichment of the KD subnetworks in MSigDB canonical pathway database. Only the top 2 functional terms are shown based on the P values with Bonferroni corrections. All the pathways shown satisfy Bonferroni-corrected P<0.01. ECM indicates extracellular matrix; KD, key driver; PPAR, peroxisome proliferator-activated receptors; and PPI, protein–protein interaction.