Table 3.
Most Perturbed Modules and Pathways by the Uricosuric Agents Benzbromarone and Benziodarone, and Relationship to Observed Toxicity Phenotypes
| Gene Set | Urico Agent Expression Rank a | PPAR Mod Expression Rank a | q-Adj Decreased Trigs b | Rank Decreased Trigs c | q-Adj Hypertrophy b | Rank Hypertrophy c |
|---|---|---|---|---|---|---|
| GO: fatty acid catabolic process | 1 | 1 | 2.64E-10 | 20 | 0.0000131 | 117 |
| DM: liver: 26 | 2 | 2 | 0.000041 | 36 | 0.000043 | 195 |
| DM: liver: 17 | 2.5 | 1.5 | 0.0000064 | 21 | 9.2E-08 | 130 |
| GO: negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway | 3 | 9 | 5.06E-08 | 26 | 2.94E-11 | 25 |
| DM: liver: 285 | 5.5 | 16.5 | 0.025 | 177 | 2.7E-12 | 73 |
| GO: coenzyme metabolic process | 5.5 | 8 | 0.0000429 | 43 | 8.73E-15 | 15 |
| REACTOME: Genes involved in destabilization of mRNA by AUF1 (hnRNP D0) | 5.5 | 7.5 | 0.00026007 | 51 | 1.15E-07 | 72 |
| REACTOME: Genes involved in metabolism of lipids and lipoproteins | 6.5 | 7 | 6.16E-13 | 7 | 0.00000173 | 92 |
a
Each pathway or module was ranked from most to least perturbed (absolute value of pathway/module score) within each of 6 uricosuric agent and 26 PPAR modulator experiments, and the rank averaged across the 6/26 experiments.
b
The adjusted q value indicating the pathway or module’s general association with the phenotype across all TGs experiments.
c
The corresponding rank for the phenotype. These are “concurrent” associations, because expression results were taken from samples where the phenotype is present. Abbreviation: Trigs, triglycerides. Full results are provided in Supplementary Dataset 5.