Table 2.
Biological pathway analyses. For top candidate biomarkers after discovery and prioritization. A. Pathways for top biomarkers with CFG score ≥ 12. B. Pathways for biomarkers with CFG score ≥ 10. C. Diseases for top biomarkers with CFG score ≥ 12. D. Diseases for biomarkers with CFG score ≥10
| DAVID GO functional annotation biological processes | KEGG pathways | Ingenuity pathways | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. | Term | Count | % | P-value | Term | Count | % | P-value | Top canonical pathways | P-value | Overlap | |
| A. Pathways CFG ≥ 12 | ||||||||||||
| Top biomarkers (n = 18 genes, 23 probeset) | 1 | Positive regulation of peptidyl-tyrosine phosphorylation | 3 | 16.7 | 3.10E−03 | Alzheimer’s disease | 5 | 27.8 | 3.80E−04 | Neuroinflammation Signaling Pathway | 3.04E−09 | 2.2 % 7/313 |
| 2 | Response to oxidative stress | 3 | 16.7 | 5.40E−03 | Lysosome | 4 | 22.2 | 2.10E−03 | Amyloid Processing | 7.61E−08 | 7.8 % 4/51 | |
| 3 | Neuron projection regeneration | 2 | 11.1 | 8.10E−03 | Glycosaminoglycan degradation | 2 | 11.1 | 4.10E−02 | Reelin Signaling in Neurons | 5.86E−05 | 3.2 % 3/94 | |
| 4 | Positive regulation of cardiac muscle cell differentiation | 2 | 11.1 | 1.00E−02 | Pathways in cancer | 4 | 22.2 | 5.00E−02 | 14-3-3-mediated Signaling | 1.87E−04 | 2.2 % 3/139 | |
| 5 | Negative regulation of blood vessel endothelial cell migration | 2 | 11.1 | 1.40E−02 | Regulation of the Epithelial-Mesenchymal Transition Pathway | 5.20E−04 | 1.5 % 3/197 | |||||
| B. Pathways CFG ≥ 10 | ||||||||||||
| Top biomarkers (n = 112 genes,138 probesets) | 1 | Cholesterol transport | 4 | 3.6 | 1.40E−04 | Alzheimer’s disease | 11 | 9.8 | 1.10E−05 | LXR/RXR activation | 1.15E−08 | 7.4 % 9/121 |
| 2 | Positive regulation of peptidyl-tyrosine phosphorylation | 6 | 5.4 | 1.90E−04 | Nonalcoholic fatty liver disease (NAFLD) | 8 | 7.1 | 1.10E−03 | Neuroinflammation signaling pathway | 6.82E−08 | 3.8 % 12/313 | |
| 3 | Cellular response to hypoxia | 6 | 5.4 | 4.00E−04 | Osteoclast differentiation | 7 | 6.2 | 2.70E−03 | Atherosclerosis Signaling | 4.14E−06 | 5.5 % 7/128 | |
| 4 | Cholesterol efflux | 4 | 3.6 | 5.50E−04 | AMPK signaling pathway | 6 | 5.4 | 1.00E−02 | Role of Macrophages, Fibroblasts and Endothelial Cells in Rheumatoid Arthritis | 6.03E−06 | 3.1 % 10/323 | |
| 5 | Cholesterol import | 3 | 2.7 | 6.20E−04 | PI3K-Akt signaling pathway | 10 | 8.9 | 1.10E−02 | Amyloid Processing | 6.05E−06 | 9.8 % 5/51 | |
| DAVID | Ingenuity pathways disease | |||||||
|---|---|---|---|---|---|---|---|---|
| No. | Term | Count | % | P-value | Diseases and disorders | P-value | Molecules | |
| C. Diseases CFG ≥ 12 | ||||||||
| Top biomarkers (n = 18 genes, 23 probeset | 1 | Alzheimer’s disease | 12 | 66.7 | 2.50E−09 | Neurological disease | 2.26E−05 to 1.40E−15 | 16 |
| 2 | Depression | 6 | 33.3 | 1.30E−06 | Organismal injury and abnormalities | 2.26E−05 to 3.26E−13 | 17 | |
| 3 | Frontotemporal dementia | 3 | 16.7 | 9.70E−06 | Metabolic disease | 2.12E−05 to 1.30E−10 | 15 | |
| 4 | Lung cancer | 7 | 38.9 | 3.30E−05 | Psychological disorders | 1.76E−05 to 1.77E−10 | 11 | |
| 5 | Breast cancer | 7 | 38.9 | 7.50E−05 | Inflammatory response | 2.05E−05 to 4.48E−10 | 15 | |
| D. Diseases CFG ≥ 10 | ||||||||
| Top biomarkers (n = 112 genes, 138 probesets) | 1 | Alzheimer’s disease | 11 | 26 | 2.10E−18 | Neurological disease | 1.27E−06 to 2.30E−21 | 76 |
| 2 | atherosclerosis | 8 | 17 | 1.00E−08 | Organismal injury and abnormalities | 1.32E−06 to 2.30E−21 | 204 | |
| 3 | cognitive trait | 7 | 10 | 2.70E−07 | Psychological disorders | 1.27E−06 to 2.30E−21 | 51 | |
| 4 | Type 2 diabetes| edema | rosiglitazone | 6 | 39 | 2.80E−07 | Metabolic disease | 1.27E−06 to 3.83E−21 | 49 | |
| 5 | Aging/telomere length | 1 | 10 | 2.90E−07 | Skeletal and muscular disorders | 1.32E−06 to 2.17E−17 | 64 | |