Meta-Analysis of Large-Scale Toxicogenomic Data Finds Neuronal Regeneration Related Protein and Cathepsin D to Be Novel Biomarkers of Drug-Induced Toxicity
Fig 5
Computational and experimental validations identify NREP and CTSD as biomarkers of toxicity in human cell lines.
(A) Density plots comparing expression levels of NREP between untreated and treated samples of liver primary hepatocytes reported in TG-GATEs. (B) Boxplots display fold-changes in CTSD (toxic/innocuous) at each of the given cell viability thresholds measured for the liver primary hepatocytes reported in TG-GATEs. * t-test p-value < 0.05, ** < 0.001. (C, D) Dose-responsive viability of HEK293 (C) and HepG2 (D) cells exposed to cisplatin (C) or acetaminophen (D). DMSO was used to dissolve the compounds. Cell viability was measured by MTS assay. Error bars represent ± standard deviation of triplicate experiments. See S4A and S4B Fig for the results with the same compounds dissolved in growth media. (E, F) NREP mRNA levels after exposure to the indicated concentrations of cisplatin for 72 h and acetaminophen for 48 h, respectively, determined by RT-PCR. (G-H) qRT-PCR assays for NREP (G) and CTSD (H). Y-axis indicates fold-changes in expression compared to chemically untreated samples (n = 5). Level-0 and level-1 drug concentrations for DMSO and DMEM were selected based on cell viability of > or < 60%, respectively, in C-D and S4A and S4B Fig. *p < 0.05, ** p < 0.001; Student’s t-test. Error bars represent ± standard deviation.