Mining a human transcriptome database for chemical modulators of NRF2
Fig 3
Characterization of the human NRF2 biomarker.
A. Identification of NRF2 biomarker genes was based on consistent directional changes in gene expression resulting from exposure to NRF2 activators sulforaphane (GSE20479 and GSE28813), oltipraz (GSE20479), sulindac (TG-GATES), and quercetin (GSE28878), and knockdown of the NRF2 negative regulator Keap1 (GSE28813). Changes in gene expression were required to be in the opposing direction in cells in which NFE2L2 (NRF2) expression was knocked down (GSE38332). The bars on the left represent the–Log (p-values) for the Running Fisher comparison test between the biomarker and the individual biosets used to construct it. The heatmap on the right depicts gene expression changes for the 143 genes in the biomarker across the individual biosets. B. Canonical pathway analysis of the biomarker genes. Multiple test correction on p-values derived from the right-tailed Fisher’s exact tests was carried out using the Benjamini-Hochberg method. The -Log(q-value)s are shown. C. Potential upstream regulators of NRF2 biomarker genes (activation z-scores > |2|). Only upstream regulators with q-values < 0.05 are shown. Both analyses were conducted using Ingenuity Pathway Analysis software.