TABLE 4.
Rank ITEa | Rank TCDDb | Gene set name | Descriptionc | # Genes in setd | FDR q valuee | Nominal p value |
1 | 6 | Dendritic cell pathway | ANPEP, several interleukins, TLRs, interferons, and CD molecules | 21 (2) | 0.047 | 0.000 |
2 | 3 | Arachidonic acid metabolism | PTGS1,2; carbonyl reductases; GGT; PTGES, PTGDS; phospholipases, Cyp2U1 and 2E1; and GPXs, … | 40 (10) | 0.138 | 0.002 |
3 | 4 | IDX TSA DN cluster1 | Genes downregulated 48–96 h during 3T3-L1 fibroblast differentiation into adipocytes with IDX (insulin, dex, and isobutylxanthine) | 40 (12) | 0.094 | 0.000 |
4 | 25 | γHexachlorocyclohexane degradation | Acid and alkaline phosphatases, Cyp3a's, and paraoxonases | 14 (4) | 0.118 | 0.000 |
5 | 2 | Fatty acid metabolism | AcylCoA dehydrogenases, oxidases, synthetases; ADHs, AldHs, many P450s, … | 60 (10) | 0.101 | 0.000 |
6 | 5 | Metabolism of xenobiotics by cytochrome P450, … | Many AldHs, Cyps, GSTs, epoxide hydrolase, and UDPGTs | 34 (7) | 0.116 | 0.002 |
7 | 1 | Prostaglandin and leukotriene metabolism | Lipoxygenases, Cyp4F's, carbonyl reductases, PTGES, and phospholipases, … | 28 (7) | 0.193 | 0.000 |
8 | 15 | Greenbaum E2A DN | E2A target genes in lymphocyte development | 25 (8) | 0.170 | 0.004 |
9 | 9 | Eicosanoid synthesis | PG synthases, arachidonate lipoxygenases, PTGS1,2 | 16 (7) | 0.153 | 0.004 |
10 | 10 | Butanoate metabolism | 27 (8) | 0.231 | 0.006 | |
11 | 43 | Pomeroy desmoplasmic versus classic MD_DN | Genes expressed in classic medulloblastomas | 37 (2) | 0.236 | 0.002 |
12 | 13 | Nicotinate and nicotinamide metabolism | 22 (8) | 0.241 | 0.006 | |
13 | 14 | Valine, leucine, and isoleucine degradation | Transferases, dehydrogenases, … | 35 (10) | 0.225 | 0.007 |
(6)f | (11) | TGFβ signaling pathway | TGFβs, TGFRs, LTBP1; bone morphogenic proteins, Id1–4; MAPK1,3; protein phosphatase 2’s; CDK inhibitor 2B | 82 (27) | 0.510 | 0.002 |
Note. Listed are the gene sets which were identified by GSEA to be enriched in ITE-treated cells compared with DMSO treated, with FDR < 25%. ADHs, alcohol dehydrogenases; AldHs, aldehyde dehydrogenases; ANPEP, alanyl aminopeptidase; GGT, g-glutamyl transpeptidase (or gamma-glutamyl transpeptidase); GPXs, glutathione peroxidases; GSTs, glutathione S-transferases; MAPK, mitogen-activated protein kinase; PG, prostaglandin; PTGS, prostaglandin endoperoxide synthase; PTGES, prostaglandin E synthase; PTGDS, prostaglandin D synthase; TLR, toll-like receptor; UDPGTs, UDP-glucuronyltransferases.
Rank within the enriched gene sets, based on normalized enrichment score (ITE vs. DMSO). Rank differs among repeated runs of GSEA due to random permutation process of analysis.
Rank within enriched gene sets (TCDD vs. DMSO).
Some of the genes/classes of genes included in indicated gene set.
Total number of genes in set (number individually induced in ITE samples).
FDR, estimated probability that set represents a false positive.
One of the sets downregulated by ITE and TCDD relative to DMSO; FDR > 25% (as it is for all downregulated sets).