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NRS 13, e002 | Figure 3

Oshida K, Vasani N, Jones C, Moore T, Hester S, Nesnow S, Auerbach S, Geter D, Aleksunes L, Thomas R, Applegate D, Klaassen D and Corton J (2015). Identification of chemical modulators of the constitutive activated receptor (CAR) in a gene expression compendium. Nucl Recept Signal 13, e002. doi:10.1621/nrs.13002




Figure 3. The CAR biomarker signature accurately predicts CAR activation. A. Heat map showing the expression of genes in the CAR biomarker signature across 468 biosets. Genes in the biomarker signature were ordered based on their average fold-change. Biosets were ordered based on their similarity to the CAR biomarker signature using the p-value of the Running Fisher’s test. Biosets with positive correlation are on the left and biosets with negative correlation are on the right. The red vertical lines denote a p-value of 10-4. B. Similarity of the CAR biomarker signature to biosets from the three chemicals used to derive the biomarker signature in wild-type but not CAR-null mice. Additional comparisons of mice expressing the human CAR gene (hCAR) expressed in the CAR-null background are shown. All p-values from comparisons of each bioset to the CAR biomarker signature were converted to –log10 values. Those comparisons which exhibited negative correlation to the biomarker signature were given a negative value. C. The CAR biomarker signature correctly identifies three known CAR activators (Aroclor-1260, PCB-153 and phenobarbital) in mice exposed to 12 diverse treatments. Open bars, females. Filled bars, males. Conditions of exposure are found in Supplemental File 1. D. Summary of the sensitivity and specificity of the CAR biomarker signature. The biomarker signature was compared to chemicals that were known positives or negatives for CAR activation.