Table 2. Pathway analysis on onion-induced differentially expressed genes in human Caco-2, rat slices and pig SISP models.
| Model(s) | process | pathway | # of genes | % match | GA score | DAVID score | genesa |
|---|---|---|---|---|---|---|---|
| Pathways affected in multiple models | |||||||
| Caco-2 and rat | oxidation | Keap1-Nrf2 Pathway | 4 | 31 | 35 | NA | GCLM, GGLC, HMOX1, NQO1 |
| Caco-2 and rat | oxidation | Oxidative stress | 3 | 9 | 21 | NA | GGLC, HMOX1, NQO1 |
| Caco-2 and rat | oxidation | Biological oxidations | 4 | 2 | 18 | NA | GCLM, GGLC, NQO1, UGDH |
| Caco-2 and rat | vitamin | One carbon pool by folate | 3 | 4 | 18 | NA | GCLM, GGLC, ABCC5 |
| Caco-2 and rat | detoxification | Glutathione metabolism | 2 | 4 | 12 | NA | GCLM, GGLC |
| Caco-2 and pig | steroid | Synthesis of bile acids and bile salts | 2 | 6 | 16 | NA | AKR1C1, AKR1C2 |
| Caco-2 and pig | steroid | Steroid hormone biosynthesis | 2 | 4 | 15 | NA | AKR1C1, AKR1C2 |
| Pathways affected in individual models | |||||||
| Rat | vitamin | Vitamin A and carotenoid metabolism | 5 | 12.5 | 15.3 | NA | RBP7, BCO2, BCMO1, ADH4, SCARB1 |
| Caco-2 | vitamin | Vitamin A and carotenoid metabolism | 3 | 7.5 | 12.0 | NA | RARB, DHRS3, ADH4 |
| Rat | vitamin | One carbon pool by folate | 7 | 10.3 | 18.8 | NA | SLC28A2, PHGDH, GCLM, GGLC, MTHFS, MTHFD1L, ABCC5 |
| Caco-2 | vitamin | One carbon pool by folate | 3 | 4.4 | 9.8 | NA | GCLM, GCLC, ABCC5 |
| Rat | sugar/energy | Glucurodination | 7 | 7.0 | 15.2 | NA | CRYL1, AKR1B1, GYS1, PGM1, G6PC, UGDH, PYGM |
| Caco-2 | sugar/energy | Glucurodination | 5 | 5.0 | 16.2 | NA | HK2, GYS2, G6PC, UGDH, XDH |
| Pig | sugar/energy | Glucose / Energy Metabolism | 2 | 1.1 | 11.6 | NA | PDX1, AKR1C2 |
| Rat | sugar/energy | Glucose / Energy Metabolism | 11 | 6.0 | 20.8 | NA | ARG1, SLC1A5, PDK1, BCAT1, PCK2, ACACA, GYS1, SCD, IDH1, ABCC2, PPARGC1A |
| Caco-2 | sugar/energy | Glucose / Energy Metabolism | 5 | 2.7 | 12.2 | NA | SLC7A11, HK2, CA2, AKR1C2, TXNRD1 |
| Rat | sugar/energy | Galactose metabolism | 5 | 13.9 | 16.0 | NA | AKR1B1, GYS1, PGM1, G6PC, PYGM |
| Caco-2 | sugar/energy | Galactose metabolism | 3 | 8.3 | 12.5 | NA | HK2, GYS2, G6PC |
| Pig | steroid | Synthesis of bile acids and bile salts | 2 | 5.7 | 16.3 | NA | AKR1C1, AKR1C2 |
| Caco-2 | steroid | Synthesis of bile acids and bile salts | 3 | 8.6 | 12.6 | NA | ACOX2, AKR1C1, AKR1C2 |
| Pig | steroid | Steroid hormone biosynthesis | 2 | 3.5 | 14.9 | NA | AKR1C1, AKR1C2 |
| Caco-2 | steroid | Steroid hormone biosynthesis | 3 | 5.3 | 10.5 | NA | AKR1C1, AKR1C2, HSD17B7 |
| Rat | oxidation | Oxidative stress | 4 | 12.5 | 12.5 | NA | GCLC, HMOX1, MAOA, NQO1 |
| Caco-2 | oxidation | Oxidative stress | 5 | 15.6 | 24.2 | NA | GCLC, HMOX1, TXNRD1, NQO1, XDH |
| Rat | oxidation | Keap1-Nrf2 Pathway | 4 | 30.8 | 17.5 | NA | GCLM, GCLC, HMOX1, NQO1 |
| Caco-2 | oxidation | Keap1-Nrf2 Pathway | 4 | 30.8 | 23.5 | NA | GCLM, GCLC, HMOX1, NQO1 |
| Rat | oxidation | HIF1-alpha transciption factor network | 5 | 7.7 | 12.0 | NA | EGLN3, HMOX1, ADM, PGM1, SMAD3 |
| Caco-2 | oxidation | HIF1-alpha transciption factor network | 3 | 4.6 | 10.0 | NA | HMOX1, HK2, SERPINE1 |
| Pig | oxidation | Biological oxidations | 2 | 0.8 | 10.8 | NA | AKR1C1, AKR1C2 |
| Rat | oxidation | Biological oxidations (REACTOME_13433) | 10 | 3.9 | NA | 0.002 | GSTA4, GCLC, PTGS2, GSTA5, MAOA, ADH4, UGDH, GCLM, GSTP1, MGST2 |
| Caco-2 | oxidation | Biological oxidations | 10 | 4.1 | 28.3 | NA | GCLM, GCLC, FMO1, AKR1C1, AKR1C2, ADH4, NAT8, GPX2, NQO1, UGDH |
| Pig | detoxification | KEGG-Metabolism of xenobiotics by cytochrome P450 | 2 | 3.3 | NA | 0.023 | AKR1C1, AKR1C2 |
| Rat | detoxification | KEGG-Metabolism of xenobiotics by cytochrome P450 | 7 | 11.7 | NA | 0.002 | GSTM2, GSTA4, GSTA5, ADH4, EPHX1, GSTP1, MGST2 |
| Caco-2 | detoxification | KEGG-Metabolism of xenobiotics by cytochrome P450 | 3 | 5.0 | NA | 0.095 | AKR1C2, ADH4, AKR1C1 |
| Rat | detoxification | Glutathione metabolism | 8 | 14.0 | 24.6 | NA | GCLM, GCLC, GSTA4, GSTA5, GSTP1, GSTM2, IDH1, MGST2 |
| Caco-2 | detoxification | Glutathione metabolism | 3 | 5.3 | 10.5 | NA | GCLM, GCLC, GPX2 |
| Rat | ECM interactions | Integrin Pathway | 17 | 3.2 | 18.1 | NA | MAPK6, ITGB6, ITGA2, ITGA2B, ITGA6, ACTA1, CCL20, CCL5, CCL24, CXCL2, CXCL10, DOCK1, JAM3, MMP7, TGFBR1, LAMC2, LAMB3 |
| Caco-2 | ECM interactions | Integrin Pathway | 7 | 1.3 | 9.9 | NA | GRB7, CACNB3, WASF1, CLDN3, SERPINE1, GNAZ, PIP5K1B |
a: genes in bold and underlined are downregulated; the non-marked genes are upregulated.