Table 5.
Differential connectivity-disease association of the low TO gene modules (low TO proteins and their direct neighbors in the PPI network).
| Number of overlapping low TO genes (overlap between coexpression and PPI network nodes) |
Number of low TO genes with higher connectivity in region (number of low TO proteins + direct neighbors in module) |
Diseases clusters |
|---|---|---|
| 113 low TO genes in EC-HIP | 63 + 5 low TO genes in EC Coexp. net (354 proteins) | Cluster 1 enrichment score = 1.31 |
| Arterial disease | ||
| Atherosclerosis, generalized blood pressure | ||
| Arterial cardiovascular disease | ||
| Esophageal varices | ||
| Cerebral white matter lesions | ||
| Peritoneal transport | ||
| 45 + 5 low TO genes in HIP Coexp. net (304 proteins) | Cluster 1 enrichment score = 0.8 | |
| Stroke, lacunar | ||
| Coronary atherosclerosis | ||
| Thromboembolism, venous | ||
| Stroke, ischemic | ||
|
| ||
| 94 low TO genes in EC-MTG | 39 + 1 low TO genes in MTG Coexp. net (428 proteins) | None |
| 54 + 1 low TO genes in EC Coexp. net (325 proteins) | Cluster 1 enrichment score = 1.15 | |
| Nephropathy | ||
| Stroke | ||
| Restenosis | ||
| Cluster 2 enrichment score = 0.98 | ||
| Panencephalitis, subacute sclerosing | ||
| Sarcoidosis; tuberculosis | ||
| Tuberculosis | ||
| Hepatitis B | ||
|
| ||
| 126 low TO genes in EC-PCC | 68 + 3 low TO genes in EC Coexp. net (405 proteins) | Cluster 1 enrichment score = 0.88 |
| Ischemia | ||
| Hyperlipidemia | ||
| Lipids | ||
| Hypercholesterolemia | ||
| 55 + 3 low TO genes in PCC Coexp. net (468 proteins) | None | |
|
| ||
| 76 low TO genes in HIP-MTG | 36 + 0 low TO genes in HIP Coexp. net (213 proteins) | None |
| 40 + 0 low TO genes in MTG Coexp. net (288 proteins ) | None | |
|
| ||
| 171 low TO genes in HIP-PCC | 94 + 3 low TO genes in HIP Coexp. net (552 proteins) | Cluster 1 enrichment score = 1.31 |
| Colon cancer; rectal cancer | ||
| Androgen levels | ||
| Hypospadias | ||
| 74 + 3 low TO genes in PCC Coexp. net (413 proteins) | Cluster 1 enrichment score = 1.31 | |
| Coronary atherosclerosis | ||
| Glomerulonephritis | ||
| Cerebrovascular disease | ||
|
| ||
| 87 low TO genes in PCC-MTG | 44 + 1 low TO genes in MTG Coexp. net (644 proteins) | None |
| 42 + 1 low TO genes in PCC Coexp. net (357 proteins) | Cluster 1 enrichment score = 0.82 | |
| Mood disorder | ||
| Smoking behavior | ||
| Alcoholism | ||
| Suicide | ||
This table provides the diseases linked with differentially connected low TO genes and direct neighbors in the PPI net. Each comparison has the following format: number of low TO genes with higher connectivity in regional Coexp. net = number of low TO genes with higher connectivity in one brain region + number of low TO genes with equal connectivity in both brain regions. For example, in the 113 EC-HIP comparison there are 113 low TO genes of which 63 genes have a higher connectivity in the EC compared to HIP coexpression network, and in addition 5 of them have equal number of connections in both coexpression networks, whereas 45 genes have a higher connectivity in the HIP with 5 extra genes having equal connectivity in both regions. The number of proteins and direct neighbors in the PPI net, that is, the module, is given in brackets. In EC HIP, 204 low TO genes ⋂ respective pruned PPI net = 113 proteins. In EC MTG, 140 low TO genes ⋂ respective pruned PPI net = 94 proteins. In EC PCC, 242 low TO genes ⋂ respective pruned PPI net = 126 proteins. In HIP MTG, 125 low TO genes ⋂ respective pruned PPI net = 76 proteins. In HIP PCC, 312 low TO genes ⋂ respective pruned PPI net = 171 proteins. In PCC MTG, 158 low TO genes ⋂ respective pruned PPI net = 87 proteins. This table reveals that MTG is not cardiovascular disease (CVD) associated. When comparing HIP and PCC, PCC is highly associated with CVD, while HIP is not. When comparing EC and PCC, EC is highly associated with CVD, while PCC is not. When comparing EC and HIP, both regions are associated with CVD. When comparing EC and MTG, EC is associated with CVD, while MTG is not. Overall, EC is the brain region mostly associated with CVD. HIP and PCC follow, and PCC might be more active in CVD than HIP. MTG is least associated with CVD of all four brain regions.