Fig. 3

Drug specific effects on transcriptome dominate dose-, time- or toxicity-induced effects. A Transcriptome data were sliced to retain all drug treatments at day 1 with different doses. The orange arrow represents the concentration gradient of data. Red squares denote the doses for six TKIs (labeled in red in B) and blue diamonds denote the doses for two TKIs (labeled in blue in B). B–D Data selected as in A were projected into the tSNE space and shown with the properties of drug, concentration, or toxicity (represented by the ATP fold changes). Darker gray corresponds to higher toxicity. E Transcriptome data were sliced to retain drug treatments at a fixed dose over 5 days. The blue arrow represents the time gradient of data. Red squares denote the time points for six TKIs (labeled in red in F) and blue diamonds denote the time points for two TKIs (labeled in blue in F). F–H Data selected as in E were projected into the tSNE space and shown with the properties of drug, time or toxicity (represented by the ATP fold changes). Toxicity that was significantly different from controls was labeled with red asterisks in H. I Principal component analysis (PCA) of transcriptome changes induced by eight TKIs. J Drug concentration of each condition projected into the PCA space. K Treatment duration of each condition projected into the PCA space. L Toxicity level of each condition defined by the percent ATP of controls projected into the PCA space. Darker gray corresponds to higher toxicity. M–N Expression of genes with top and bottom 30 highest loadings of PC1 and PC2 grouped by drugs