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

Table 4

Disease associations of sets of low TO genes with (extended set) and without (primary set) their direct neighbors in the PPI networks.

Region PPI network	Disease association of low TO genes; and neighbors in PPI net	Disease association of low TO genes only
EC-HIP	Cluster 1 enrichment score = 0.96	Cluster 1
	Hypertension	Cardiovascular
	Arterial disease
	Atherosclerosis
	Kidney disease
	Vascular dementia
	Diabetic nephropathy
EC-PCC	Cluster 1 enrichment score = 0.93	Cluster 1
	Hyperlipidemia	Ischemic stroke, renal, atherosclerosis
	Coronary artery disease risk
	Cholesterol
	Cluster 2 enrichment score = 0.91	Cluster 2
	Heart related conditions	Cancer
	Alzheimer's disease	Macular degeneration
EC-MTG	Cluster 1 enrichment score = 0.89
	Insulin, cholesterol
	Type 2 diabetes, hypertension
	Polycystic ovary syndrome
HIP-PCC	Cluster 1 enrichment score = 0.82	Cluster 1
	Colon cancer, rectal cancer	Crohn's disease, atherosclerosis, ischemic stroke, renal
PCC-MTG	Cluster 1 enrichment score = 0.99
	Type 2 diabetes
	Hypertension
	Cholesterol
	Polycystic ovary syndrome
HIP-MTG	Cluster 1 enrichment score = 1.23
	Colon cancer, rectal cancer
	Male infertility

The low TO genes are proteins in the region PPI network. Column 1 shows the diseases associated with the low TO proteins and their direct neighbors in the regional PPI network while column 2 shows the diseases associated with only the low TO genes (without their neighbors). Disease databases used: OMIM disease, genetic association disease database. Similarity threshold for clustering = 0.80. Results reported only for the clusters with enrichment score 0.8 or higher. In this analysis, the low TO genes were not divided into 2 groups based on which regional coexpression network they had a higher connectivity in.