Fig. 3

(a) The heatmap on the left depicts the responses of the TGx-DDI biomarker genes in the 28 reference chemicals used to generate it by DNA microarray analysis in TK6 cells, and the test chemicals assessed with AmpliSeq in HepaRG™ cells are shown in the subsequent columns. The labels on the far right hand side are Gene Symbols corresponding to the GenBank accession numbers for the biomarker genes. The color scale indicates fold changes relative to control: up-regulated genes are in red, down-regulated genes in green, and genes exhibiting no changes relative to controls are in black. Predictions of DDI/non-DDI and NSC classification probabilities for all treatment conditions are shown using red (DDI) and blue (non-DDI) bars above each heatmap. (b) Principal component analysis using the TGx-DDI biomarker for TK6 cells exposed to the training set of chemicals (red text = DDI training set; blue text = non-DDI training set) and for HepaRG™ cells exposed to 10 test chemicals at low, mid, and high concentrations 7 h following the last exposure (green text = replicates of test agent). The line drawn at 0 on the PCA plot divides the DDI and non-DDI agents and was used for classification. (c) Hierarchical clustering of the chemicals with TGx-DDI, with color coding as in panel B. The main branch on the dendrogram separates the DDI and non-DDI agents and was used for classification of the test agent