Transcriptional regulation of lipid metabolism alterations and metabolic adaptation toward production of NADPH. A, Transcription regulator activity analysis indicates upregulation of SREBP and C/EBP transcriptional activities with CS exposure. Each row of the heatmap represents the predicted activity of a transcriptional regulator, each column represents an exposure group compared to sham exposure at the same time point. The perturbation strength is color-coded and statistical significance is indicated (*BH-adjusted P-value < .05). B, Quantitative scores of exposure effects on the entire NFE2L2 signaling pathway. The bars show the overall network perturbation amplitude (NPA), the error bars show the 95% confidence interval. Three statistics are included: the red star indicates statistical significance with respect to the biological replicates, the green star (o statistics) indicates significance with respect to permutation of the downstream genes of the network nodes, and the blue star (k statistics) indicates significance with respect to permutation of the NFEL2 network topology. C, Upregulation of proteins involved in NADPH generation by CS exposure. Heat map representation is as described in Figure 2C. D, Proteins implicated in reactive oxygen species response. The human orthologs of differentially expressed proteins of the “Hallmark Reactive Oxygen Species Pathway” are shown (www.broadinstitute.org/gsea/msigdb).