| Up-regulation |
Down-regulation |
| A. Top five up- and down-regulated network functions (network scores*) |
| 1. Cell signaling, cell death, post-translational modification (35) |
1. Genetic disorder, neurological disease, cell-to-cell signaling and interaction (43) |
| 2. Cell cycle, cellular assembly and organization, cancer (35) |
2. Organism injury and abnormalities, reproductive system disease, skeletal and muscular system (41) |
| 3. Developmental disorder, neurological disease, cardiovascular system development and function (34) |
3. Endocrine system disorder, genetic disorder, metabolic disease (32) |
| 4. Cell signaling, DNA replication, recombination, and repair, nucleic acid metabolism (30) |
4. Cell-to cell signaling and interaction, tissue development, cellular movement (29) |
| 5. Connectible tissue disorder, genetic disorder, dermatological diseases and conditions (26) |
5. Dermatological diseases and conditions, genetic disorder, cancer (21) |
| B. Top five up- and down-regulated canonical pathways (p values†) |
| 1. Caveolae-mediated endocytosis signaling (2.83E-07) |
1. Molecular mechanisms of cancer (1.93E-04) |
| 2. Protein kinase A signaling (1.02E-05) |
2. Acute myeloid leukemia signaling (2.95E-04) |
| 3. EGF signaling (8.92E-05) |
3. Erythropoietin signaling (1.16E-03) |
| 4. GNRH signaling (1.67E-04) |
4. Mechanisms of viral exit from host cells (1.23E-03) |
| 5. Cardiac β-adrenergic signaling (2.69E-04) |
5. IL-3 signaling (1.5E-03) |
| C. Top five up- and down-regulated tox lists (p values†) |
| 1. Increase glomercular injury (1.06E-02) |
1. VDR/RXR activation (1.36E-02) |
| 2. Hepatic fibrosis (1.2E-02) |
2. G2/M DNA damage checkpoint regulation (1.9E-02) |
| 3. Renal necrosis/cell death (3.11E-02) |
3. Cardiac fibrosis (2.6E-02) |
| 4. TR/RXR activation (4.99E-02) |
4. PPARα/RXRα activation (5.11E-02) |
| 5. RXR/RXR activation (9.64E-02) |
5. p53 signaling pathway (1.88E-02) |
| D. Top five up- and down-regulated canonical functions |
| 1. Cardiovascular-cancer-respiratory |
1. Epithelial cell differentiation signaling |
| 2. Clathrin-mediated endocytosis |
2. Cartilage & Cerellum & Lung development |
| 3. Immune response & Oxidative stress & Pulmonary hypertension |
3. Mitogen-activated protein kinases signaling |
| 4. Non-small cell lung cancer |
4. Transforming growth factor ß (TGF- ß)signaling |
| 5. Neurotransmitter & collagen synthesis |
5. Tumor suppressor & Angiogenesis inhibition |
*network scores given in the parentheses were based in the hyper geometric distribution and were calculated with the right-tailed Fisher’s Exact Test. The scores were not
an indication of the quality or biological relevance of the network; they simply measured the approximate “fit” between each network and the network eligible molecules.
