Table 6.
Ingenuity Canonical Signaling Pathway analysis of proteins differentially regulated in the hippocampus of aged BTBR compared to WT controls.
| Canonical pathways | −log(p-value) | Ratio | 10 × Hybrid |
|---|---|---|---|
| Oxidative phosphorylation | 1.27E + 01 | 1.25E–01 | 15.875 |
| Mitochondrial dysfunction | 1.33E + 01 | 8.37E–02 | 11.1321 |
| GABA receptor signaling | 5.19E + 00 | 1.07E–01 | 5.5533 |
| Glutamate degradation III (via 4-aminobutyrate) | 3.02E + 00 | 1.67E–01 | 5.0434 |
| GM-CSF signaling | 4.44E + 00 | 8.82E–02 | 3.91608 |
| Huntington's disease signaling | 6.46E + 00 | 5.16E–02 | 3.33336 |
| G protein signaling mediated by Tubby | 3.47E + 00 | 9.09E–02 | 3.15423 |
| Melatonin signaling | 4.18E + 00 | 7.41E–02 | 3.09738 |
| RhoA signaling | 4.52E + 00 | 6.25E–02 | 2.825 |
| Lipid antigen presentation by CD1 | 2.68E + 00 | 1.00E–01 | 2.68 |
| Regulation of actin-based motility by rho | 3.77E + 00 | 6.52E–02 | 2.45804 |
| Role of NFAT in cardiac hypertrophy | 4.87E + 00 | 4.78E–02 | 2.32786 |
| CTLA4 Signaling in cytotoxic T lymphocytes | 3.63E + 00 | 6.25E–02 | 2.26875 |
| TCA Cycle II (Eukaryotic) | 2.90E + 00 | 7.50E–02 | 2.175 |
| Breast cancer regulation by stathmin1 | 4.65E + 00 | 4.67E–02 | 2.17155 |
| Chemokine signaling | 3.22E + 00 | 6.67E–02 | 2.14774 |
| Synaptic long term potentiation | 3.72E + 00 | 5.38E–02 | 2.00136 |
| Guanine and guanosine salvage I | 1.71E + 00 | 1.11E–01 | 1.8981 |
| CREB signaling in neurons | 4.21E + 00 | 4.35E–02 | 1.83135 |
| β-alanine degradation I | 1.71E + 00 | 1.00E–01 | 1.71 |
| Axonal guidance signaling | 5.19E + 00 | 3.29E–02 | 1.70751 |
| GNRH signaling | 3.51E + 00 | 4.58E–02 | 1.60758 |
| Actin nucleation by ARP-WASP complex | 2.65E + 00 | 5.97E–02 | 1.58205 |
| 4-Aminobutyrate degradation I | 1.53E + 00 | 1.00E–01 | 1.53 |
| Superpathway of inositol phosphate compounds | 3.94E + 00 | 3.85E–02 | 1.5169 |
| Creatine-phosphate biosynthesis | 1.32E + 00 | 1.11E–01 | 1.4652 |
| Pyruvate fermentation to lactate | 1.32E + 00 | 1.11E–01 | 1.4652 |
| D-myo-inositol-5-phosphate metabolism | 3.32E + 00 | 4.32E–02 | 1.43424 |
| fMLP signaling in neutrophils | 3.13E + 00 | 4.55E–02 | 1.42415 |
| Methylglyoxal degradation I | 1.53E + 00 | 9.09E–02 | 1.39077 |
| Clathrin-mediated endocytosis signaling | 3.29E + 00 | 4.04E–02 | 1.32916 |
| Ephrin receptor signaling | 3.45E + 00 | 3.81E–02 | 1.31445 |
| Protein kinase A signaling | 3.95E + 00 | 3.18E–02 | 1.2561 |
| Thrombin signaling | 3.20E + 00 | 3.79E–02 | 1.2128 |
| 3-phosphoinositide biosynthesis | 3.10E + 00 | 3.87E–02 | 1.1997 |
| D-myo-inositol (1,4,5,6)-tetrakisphosphate biosynthesis | 2.86E + 00 | 4.17E–02 | 1.19262 |
| D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis | 2.86E + 00 | 4.17E–02 | 1.19262 |
| Methylmalonyl pathway | 1.41E + 00 | 8.33E–02 | 1.17453 |
| Neuropathic pain signaling in dorsal horn neurons | 2.50E + 00 | 4.59E–02 | 1.1475 |
| G beta gamma signaling | 2.73E + 00 | 4.13E–02 | 1.12749 |
| nNOS signaling in neurons | 1.95E + 00 | 5.77E–02 | 1.12515 |
| Signaling by rho family GTPases | 3.24E + 00 | 3.36E–02 | 1.08864 |
| Arginine degradation I (arginase pathway) | 1.41E + 00 | 7.69E–02 | 1.08429 |
| Ephrin B signaling | 2.21E + 00 | 4.88E–02 | 1.07848 |
| Purine nucleotides de novo biosynthesis II | 2.22E + 00 | 4.76E–02 | 1.05672 |
| Leptin signaling in obesity | 2.19E + 00 | 4.71E–02 | 1.03149 |
| Semaphorin signaling in neurons | 1.83E + 00 | 5.56E–02 | 1.01748 |
| Inosine-5′-phosphate biosynthesis II | 1.53E + 00 | 6.25E–02 | 0.95625 |
| Actin cytoskeleton signaling | 2.88E + 00 | 3.31E–02 | 0.95328 |
| 3-phosphoinositide degradation | 2.57E + 00 | 3.70E–02 | 0.9509 |
| Rac signaling | 2.43E + 00 | 3.91E–02 | 0.95013 |
| iCOS-iCOSL signaling in T helper cells | 2.38E + 00 | 3.97E–02 | 0.94486 |
| Dopamine receptor signaling | 2.17E + 00 | 4.17E–02 | 0.90489 |
| Molybdenum cofactor biosynthesis | 1.41E + 00 | 6.25E–02 | 0.88125 |
| Aldosterone signaling in epithelial cells | 2.38E + 00 | 3.55E–02 | 0.8449 |
| CD28 signaling in T helper cells | 2.23E + 00 | 3.68E–02 | 0.82064 |
| B cell receptor signaling | 2.30E + 00 | 3.43E–02 | 0.7889 |
| 2-oxobutanoate degradation I | 1.32E + 00 | 5.88E–02 | 0.77616 |
| PKCθ signaling in T lymphocytes | 2.23E + 00 | 3.47E–02 | 0.77381 |
| Virus entry via endocytic pathways | 1.93E + 00 | 3.96E–02 | 0.76428 |
| P2Y purigenic receptor signaling pathway | 2.14E + 00 | 3.47E–02 | 0.74258 |
| D-myo-inositol (1,4,5)-trisphosphate biosynthesis | 1.48E + 00 | 5.00E–02 | 0.74 |
| Dopamine-DARPP32 feedback in cAMP signaling | 2.25E + 00 | 3.21E–02 | 0.72225 |
| PI3K signaling in B lymphocytes | 2.05E + 00 | 3.50E–02 | 0.7175 |
| α-Adrenergic signaling | 1.95E + 00 | 3.67E–02 | 0.71565 |
| Protein ubiquitination pathway | 2.41E + 00 | 2.96E–02 | 0.71336 |
| Gluconeogenesis I | 1.67E + 00 | 4.26E–02 | 0.71142 |
| Glutamate receptor signaling | 1.69E + 00 | 4.17E–02 | 0.70473 |
| G-Protein coupled receptor signaling | 2.38E + 00 | 2.90E–02 | 0.6902 |
| IL-1 signaling | 1.87E + 00 | 3.67E–02 | 0.68629 |
| Antiproliferative role of somatostatin receptor 2 | 1.60E + 00 | 4.17E–02 | 0.6672 |
| Remodeling of epithelial adherens junctions | 1.53E + 00 | 4.29E–02 | 0.65637 |
| JAK/stat signaling | 1.54E + 00 | 4.23E–02 | 0.65142 |
| Glioma signaling | 1.84E + 00 | 3.54E–02 | 0.65136 |
| Role of NFAT in regulation of the immune response | 2.15E + 00 | 3.00E–02 | 0.645 |
| Fatty acid β-oxidation I | 1.45E + 00 | 4.44E–02 | 0.6438 |
| RhoGDI signaling | 2.11E + 00 | 2.97E–02 | 0.62667 |
| Cardiac β-adrenergic signaling | 1.96E + 00 | 3.16E–02 | 0.61936 |
| Cardiac hypertrophy signaling | 2.15E + 00 | 2.80E–02 | 0.602 |
| Relaxin signaling | 1.93E + 00 | 3.05E–02 | 0.58865 |
| Renal cell carcinoma signaling | 1.50E + 00 | 3.80E–02 | 0.57 |
| Calcium signaling | 2.05E + 00 | 2.76E–02 | 0.5658 |
| Phospholipase C signaling | 2.06E + 00 | 2.64E–02 | 0.54384 |
| Gαq signaling | 1.80E + 00 | 2.92E–02 | 0.5256 |
| Gαs signaling | 1.60E + 00 | 3.20E–02 | 0.512 |
| Molecular mechanisms of cancer | 2.15E + 00 | 2.32E–02 | 0.4988 |
| Role of tissue factor in cancer | 1.61E + 00 | 3.08E–02 | 0.49588 |
| Gap junction signaling | 1.71E + 00 | 2.76E–02 | 0.47196 |
| p70S6K signaling | 1.51E + 00 | 3.03E-02 | 0.45753 |
| Androgen signaling | 1.60E + 00 | 2.76E–02 | 0.4416 |
| Gαi signaling | 1.48E + 00 | 2.96E–02 | 0.43808 |
| cAMP-mediated signaling | 1.65E + 00 | 2.65E–02 | 0.43725 |
| PPARα/RXRα activation | 1.51E + 00 | 2.50E–02 | 0.3775 |
| Insulin receptor signaling | 1.38E + 00 | 2.68E–02 | 0.36984 |
| eNOS signaling | 1.39E + 00 | 2.58E–02 | 0.35862 |
| Glucocorticoid receptor signaling | 1.35E + 00 | 2.01E–02 | 0.27135 |
Canonical signaling pathway annotation of the hippocampal proteins possessing BTBR:WT iTRAQ expression ratios < 1.2 or < 0.8 was created using Ingenuity Pathway Analysis. Each signaling pathway significantly populated (p < 0.05) by at least two independent proteins are depicted. For each populated signaling pathway the −log10 of the enrichment probability (p-value), the enrichment ratio and the calculated hybrid score [10 * (enrichment ratio * −log10(p-value))] are depicted.