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

Table 6

Disease association of the pairs of low TO gene modules in Soler-López et al.'s AD PPI network.

Number of overlapping; low TO genes	Number of low TO genes with; high connectivity in region; (number of proteins in low TO modules)	Enriched disease clusters
15 EC-HIP	9 + 1 low TO genes in EC (67 proteins)	Cluster 1 enrichment score = 1.88
		Arterial disease
		Atherosclerosis, generalized blood pressure
		Arterial cardiovascular disease
		Cerebral white matter lesions
		Esophageal varices
		Peritoneal transport
	5 + 1 low TO genes in HIP (35 proteins)	None
21 EC-MTG	12 + 0 low TO genes in EC (60 proteins)	None
	9 + 0 low TO genes in MTG (125 proteins)	None
23 EC-PCC	12 + 0 low TO genes in EC (66 proteins)	None
	11 + 0 low TO genes in PCC (88 proteins)	Cluster 1 enrichment score = 0.98
		Coronary atherosclerosis
		Lipoprotein
		Cardiovascular disease
		Myocardial infarction
		Cluster 2 enrichment score = 0.88
		Lipoprotein
		Myocardial infarction
		Coronary artery disease
		Atherosclerosis, coronary
12 HIP-MTG	5 + 0 low TO genes in HIP (18 proteins)	Cluster 1 enrichment score = 0.9
		Prostate cancer
		Breast cancer
		Pharmacogenomic
		Cancer
	7 + 0 low TO genes in MTG (37 proteins)	None
27 HIP-PCC	12 + 1 low TO genes in PCC (58 proteins)	Cluster 1 enrichment score = 1.58
		Coronary artery disease
		Stroke
		Crohn's disease ulcerative colitis
		Restenosis
		Cluster 2 enrichment score = 0.83
		Melanoma
		Stomach cancer
		Asthma
	14 + 1 low TO genes in HIP (95 proteins)	None
16 PCC-MTG	6 + 1 low TO genes in PCC (47 proteins)	None
	9 + 1 low TO genes in MTG (112 proteins)	None

Number of low TO genes with high connectivity in regional coexpression network = number of low TO genes with higher connectivity in one brain region + number of low TO genes with equal connectivity in both brain regions. There are 1704 proteins in ADnet. In EC HIP, 204 low TO genes ⋂ ADnet = 15 proteins. In EC MTG, 140 low TO genes ⋂ ADnet = 21 proteins. In EC PCC, 242 low TO genes ⋂ ADnet = 23 proteins. In HIP MTG, 125 low TO genes ⋂ ADnet = 12 proteins. In HIP PCC, 312 low TO genes ⋂ ADnet = 27 proteins. In PCC MTG, 158 low TO genes ⋂ ADnet = 16 proteins. Disease annotation cluster analysis was conducted on pairs of exclusive low TO modules (pairs of low TO modules excluding common proteins between module pairs). MTG seems to be least associated with cardiovascular diseases (CVD). When comparing EC and HIP, EC is highly associated with CVD. When comparing EC and PCC, PCC is highly associated with CVD. When comparing HIP and PCC, PCC is highly associated with CVD.