Research Article

Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

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.