Table 10. An alternative approach based on a predefined group of genes (metabolic and signaling pathways in KEGG) was used to evaluate differential pathway activities at each time point, post treatment, compared to the control animals.
| Pathway | SM24* | SMI-24† | SM72* | SMI-72† | SM 168* | SMI-168† |
|---|---|---|---|---|---|---|
| Neurodegenerative disorders | 0.039 | 0.5694 | 0.9517 | 0.7433 | 0.7808 | 0.8799 |
| Thiamine metabolism | 0.04 | 0.1504 | 0.008 | 0.1052 | 0.2437 | 0.1894 |
| Glioma | 0.042 | 0.6121 | 0.9976 | 0.9944 | 0.9824 | 0.9977 |
| Cytokine-cytokine receptor interaction | 0.0456 | 0.0687 | 0.5258 | 0.0022 | 0.4987 | 0.0035 |
| Terpenoid biosynthesis | 0.047 | 0.0701 | 0.0011 | 0.0103 | 0.019 | 0.0008 |
| Methane metabolism | 0.0489 | 0.1945 | 0.0238 | 0.0809 | 0.4053 | 0.0456 |
| Fatty acid biosynthesis | 0.088 | 0.0296 | 0.02 | 0.001 | 0.0107 | 0.0041 |
| Purine metabolism | 0.1679 | 0.0299 | 0.7888 | 0.9612 | 0.6399 | 0.8637 |
| Urea cycle and metabolism of amino groups | 0.1408 | 0.031 | 0.9106 | 0.8238 | 0.3617 | 0.1675 |
| Arachidonic acid metabolism | 0.3127 | 0.0339 | 0.5819 | 0.0206 | 0.0565 | 0.2192 |
| Aminosugars metabolism | 0.2458 | 0.0393 | 0.2348 | 0.3673 | 0.1453 | 0.3668 |
| Cell communication | 0.337 | 0.0427 | 0.376 | 0.0164 | 0.0564 | 0.075 |
| Taurine and hypotaurine metabolism | 0.2754 | 0.0429 | 0.9024 | 0.6113 | 0.5074 | 0.2642 |
| Glycosylphosphatidylinositol | 0.4842 | 0.048 | 0.7613 | 0.5648 | 0.8792 | 0.2443 |
| Nicotinate and nicotinamide metabolism | 0.2134 | 0.1421 | 0.0032 | 0.1505 | 0.1291 | 0.3936 |
| Bile acid biosynthesis | 0.6092 | 0.1469 | 0.0032 | 0.0214 | 0.0486 | 0.0336 |
| Riboflavin metabolism | 0.1653 | 0.1599 | 0.004 | 0.1066 | 0.0129 | 0.2346 |
| 1- and 2-Methylnaphlhalene degradation | 0.1686 | 0.1244 | 0.0046 | 0.0497 | 0.0196 | 0.0486 |
| Fatty acid elongation in mitochondria | 0.3335 | 0.5421 | 0.0083 | 0.1426 | 0.5593 | 0.2223 |
| Metabolism of xenobiotics by cytochrome P450 | 0.6824 | 0.2559 | 0.0116 | 0.06 | 0.4679 | 0.1099 |
| Lysine degradation | 0.4443 | 0.487 | 0.0132 | 0.0467 | 0.2505 | 0.117 |
| Fatty acid metabolism | 0.3226 | 0.2493 | 0.014 | 0.0486 | 0.1827 | 0.1152 |
| gamma-Hexachlorocyclohexane degradation | 0.3418 | 0.158 | 0.018 | 0.049 | 0.0495 | 0.055 |
| Sulfur metabolism | 0.6127 | 0.5662 | 0.0223 | 0.671 | 0.3992 | 0.2367 |
| Tryptophan metabolism | 0.7325 | 0.2778 | 0.0266 | 0.07 | 0.603 | 0.1552 |
| Styrene degradation | 0.2302 | 0.06 | 0.0278 | 0.0916 | 0.264 | 0.0721 |
| Carbazole degradation | 0.8657 | 0.7966 | 0.0281 | 0.18 | 0.0181 | 0.0244 |
| Androgen and estrogen metabolism | 0.8155 | 0.3289 | 0.0293 | 0.1141 | 0.6005 | 0.1842 |
| Reductive carboxylate cycle | 0.3027 | 0.3365 | 0.0367 | 0.0886 | 0.189 | 0.2233 |
| Glutathione merabolism | 0.355 | 0.3515 | 0.0405 | 0.1432 | 0.2103 | 0.2079 |
| 1,1,1-Trichloro-2,2-bis | 0.9007 | 0.8062 | 0.0435 | 0.2153 | 0.0213 | 0.0342 |
| Valine, leucine and isoleucine degradation | 0.7407 | 0.231 | 0.0438 | 0.0322 | 0.1719 | 0.0539 |
| 2,4-Dichlorobenzoate degradation | 0.8281 | 0.3744 | 0.0462 | 0.1379 | 0.0491 | 0.0327 |
| Eenzoate degradation via CoA ligation | 0.298 | 0.2447 | 0.047 | 0.0403 | 0.1013 | 0.0856 |
| Hematopoietic cell lineage | 0.5299 | 0.071 | 0.0476 | 0.8882 | 0.7409 | 0.1487 |
| Synthesis and degradation of ketone bodies | 0.6306 | 0.2081 | 0.0954 | 0.0163 | 0.0537 | 0.0238 |
| Pantothenate and CoA biosynthesis | 0.3431 | 0.1294 | 0.1956 | 0.0213 | 0.097 | 0.0085 |
| Propanoate metaboiism | 0.1823 | 0.1216 | 0.0747 | 0.0287 | 0.0852 | 0.0507 |
| Butanoate metabolism | 0.8944 | 0.2828 | 0.1042 | 0.0294 | 0.1885 | 0.0544 |
| Biosynthesis of steroids | 0.189 | 0.1281 | 0.0525 | 0.0295 | 0.0856 | 0.0238 |
| Linoleic acid metabolism | 0.1662 | 0.351 | 0.2802 | 0.033 | 0.1353 | 0.098 |
| Lysine biosynthesis | 0.4334 | 0.0943 | 0.4849 | 0.0332 | 0.2065 | 0.0709 |
| Glycine, serine and threonine metabolism | 0.639 | 0.3086 | 0.1198 | 0.0363 | 0.1768 | 0.0851 |
| Pyruvate metabolism | 0.5949 | 0.7417 | 0.1988 | 0.0371 | 0.1988 | 0.067 |
| ABC transporters - general | 0.2504 | 0.2368 | 0.3741 | 0.4469 | 0.0185 | 0.2165 |
| Circadian rhythm | 0.1174 | 0.0515 | 0.3505 | 0.2296 | 0.0414 | 0.0762 |
| Inositol metabolism | 0.0754 | 0.0517 | 0.1752 | 0.7487 | 0.3397 | 0.029 |
| Vitamin BS metabolism | 0.4674 | 0.2128 | 0.5157 | 0.0751 | 0.08 | 0.0325 |
Inhibitor treated animals show different pathway activities for 24 h exposure. For later responses transcriptional profiles for sulfur mustard treated and inhibitor treated samples overlap. Even though there was no significant histological difference between the SM and SM-I (i.e. with inhibitor) cases, the differential pathway activities identified here can provide insight into the time course progression of gene expression. The table depicts the p-values associated with the confidence level that there was significant change in the activity of a particular pathway under a specific condition. Gray shaded entries correspond to p-values less than 0.05 and hence express confidence that a particular pathway was indeed altered at that condition.
*
Exposure to sulfur mustard only.
†
Exposure to Sulfur Mustard plus Inhibitor.