Table 3.
Results of the paired class comparison analysis between baseline and stress time points using BioCarta and KEGG pathways as defined gene sets. Pathways containing more than five genes present on the array were included in the analysis. This meant that 176 BioCarta and 146 KEGG pathways were considered. A univariate analysis using paired t-tests with a random variance model was run to determine the differentially expressed genes in each gene set. Significant gene sets were then identified with summary statistics (the LS/KS permutation test and Efron–Tishirani's maxmean test (Efron and Tishirani, 2007) using a threshold of 0.05 for at least one test. In the combined BioCarta/KEGG analysis 49 pathways passed this threshold. Pathways in highlighted in bold are common to both the baseline-stress and stress–recovery analyses. p-Values and Log ratios are presented in Supplementary file 1.
| Pathway ID | Pathway description | No. of genes | Biological function | |
|---|---|---|---|---|
| 1 | h_ucalpain | uCalpain and friends in Cell spread | 11 | Adhesion |
| 2 | h_agr | Agrin in postsynaptic differentiation | 19 | Adhesion, cell migration |
| 3 | h_ecm | Erk and PI-3 kinase are necessary for collagen binding in corneal epithelia | 10 | Adhesion, cell migration |
| 4 | h_rho | Rho cell motility signaling pathway | 13 | Adhesion, cell morphology |
| 5 | h_rac1 | Rac 1 cell motility signaling pathway | 10 | Adhesion, cell signaling |
| 6 | hsa05040 | Huntington's disease | 13 | Apoptosis |
| 7 | h_ras | Ras signaling pathway | 8 | Apoptosis |
| 8 | h_intrinsic | Intrinsic prothrombin activation pathway | 6 | Blood collection |
| 9 | hsa04110 | Cell cycle | 43 | Cell cycle |
| 10 | h_g1 | Cell cycle: G1/S check point | 9 | Cell cycle |
| 11 | h_skp2e2f | E2F1 destruction pathway | 5 | Cell cycle |
| 12 | h_RacCycD | Influence of Ras and Rho proteins on G1 to S Transition | 12 | Cell cycle |
| 13 | h_p27 | Regulation of p27 phosphorylation during cell cycle progression | 7 | Cell cycle progression |
| 14 | hsa04120 | Ubiquitin mediated proteolysis | 15 | Cell cycle, immune response |
| 15 | h_pml | Regulation of transcriptional activity by PML | 15 | Cell growth, apoptosis |
| 16 | h_At1r | Angiotensin II mediated activation of JNK Pathway via Pyk2 | 16 | Cell migration |
| 17 | h_mrp | Multi-drug resistance factors | 6 | Cell regulation |
| 18 | h_cardiacegf | Role of EGF receptor transactivation by GPCRs in cardiac hypertrophy | 6 | Cell regulation |
| 19 | hsa04540 | Gap junction | 35 | Cell signaling |
| 20 | h_gpcr | Signaling pathway from G-protein families | 10 | Cell signaling |
| 21 | h_erk | Erk1/Erk2 MAPK signaling pathway | 13 | Cell signaling, cell growth and differentiation |
| 22 | h_calcineurin | Effects of calcineurin in keratinocyte differentiation | 5 | Cell signaling: Ca++ |
| 23 | hsa04630 | JAK/STAT signaling pathway | 56 | Cell signaling: cytokines, growth factors, stress |
| 24 | hsa04310 | Wnt signaling pathway | 48 | Cell signaling: development, proliferation, mobility |
| 25 | h_pelp1 | Pelp1 modulation of estrogen receptor activity | 5 | Cell signaling: growth factor signaling |
| 26 | hsa04010 | MAPK signaling pathway | 114 | Cell signaling: growth, inflammation, apoptosis |
| 27 | h_fcer1 | Fc epsilon receptor I signaling in mast cells | 12 | Cell signaling: immunity, arachadonic acid metabolism |
| 28 | hsa04330 | Notch signaling pathway | 17 | Cell signaling: T-cell development |
| 29 | h_hes | Segmentation clock | 8 | Cell signaling: WNT and Notch |
| 30 | hsa00790 | Folate biosynthesis | 14 | Cofactor biosynthesis |
| 31 | h_ppara | Mechanism of gene regulation by peroxisome proliferators via PPARa | 20 | Gene regulation |
| 32 | h_sppa | Aspirin blocks signaling pathway involved in platelet activation | 6 | Hemostasis |
| 33 | hsa04650 | Natural killer cell mediated cytotoxicity | 64 | Immune response: NK cell |
| 34 | h_dc | Dendritic cells in regulating TH1 and TH2 development | 5 | Immune response: T-cell |
| 35 | h_tcr | T cell receptor signaling pathway | 14 | Immune response: T-cell |
| 36 | h_mef2d | Role of MEF2D in T-cell apoptosis | 5 | Immune response: T-cell; apoptosis |
| 37 | hsa04730 | Long-term depression | 32 | Learning and memory |
| 38 | hsa04720 | Long-term potentiation | 28 | Learning and memory |
| 39 | hsa00380 | Tryptophan metabolism | 41 | Metabolism: Amino acid |
| 40 | hsa00530 | Aminosugars metabolism | 6 | Metabolism: carbohydrate |
| 41 | hsa00053 | Ascorbate and aldarate metabolism | 9 | Metabolism: carbohydrate |
| 42 | hsa00190 | Oxidative phosphorylation | 43 | Metabolism: energy production |
| 43 | hsa00770 | Pantothenate and CoA biosynthesis | 8 | Metabolism: fatty acid |
| 44 | hsa00531 | Glycosaminoglycan degradation | 10 | Metabolism: glucosamine |
| 45 | hsa00534 | Heparan sulfate biosynthesis | 7 | Metabolism: glucosamine |
| 46 | hsa00604 | Glycosphingolipid biosynthesis - ganglioseries | 9 | Metabolism: glycolipid |
| 47 | hsa00960 | Alkaloid biosynthesis II | 16 | Metabolism: secondary metabolites |
| 48 | h_prc2 | PRC2 complex long-term gene silencing by modification of histone tails | 7 | Regulation gene expression |
| 49 | h_arap | ADP-ribosylation factor | 10 | Vesicular trafficking |