Anne-Marie Koop

40 Changes in gene expression specifically associated with either PAB+CF or PAB- 1,666 genes and 104 gene sets were specifically regulated in PAB+CF, many of which related to cellular (energy) metabolism ( figure 6 , supplemental table 1 , table supplemental table 3 ). Most prominently, there was a significant down regulation of glycolysis/gluconeogenesis related gene sets in PAB+CF, in contrast to PAB- ( figure 7 ). In addition, while the changes in fatty acid metabolism and beta-oxidation were comparable between PAB- and PAB+CF, the down regulation of oxidative phosphorylation, the tricarboxylic acid cycle and amino acid metabolism appeared to be more pronounced in PAB-CF than in PAB- ( figure 7 ). In contrast to the PAB+CF group, only a few additional genes (215) and gene sets (20) were specifically regulated in PAB- ( figure 6 , supplemental table 1 ). The 215 genes were not significantly related to a specific biological process. Likewise, the found gene sets were aspecific. No gene sets were regulated in opposite directions in PAB- vs. PAB+CF. Figure 6. Significantly regulated gene sets in CON, PAB- and PAB+CF. Gene set enrichment analysis. Number of differentially enriched gene sets vs. CON in PAB-and PAB+CF is indicated in the circles, separately for positive/ negative enrichment (up regulation/down regulation). Commonly enriched gene sets are represented by the overlap. Pie-charts show distribution of the gene sets in categories for PAB-, PAB+CF and COMMON, again separately for positive/negative enrichment. N=7/4/5 for CON/PAB-/PAB+CF. False discovery rate (FDR) <15%, nominal P value <0.05 and normalized enrichment score >1.3 was considered significant.

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