Figure 4
Evaluations of Trametinib and Cisplatin in TDS expression. Trametinib and Cisplatin were used to test the TDS screening system. In each plot, differential expression of TDS genes between tg-mel and wt medaka were plotted in ascending order of TDS Log2FC values (black dots). Gene expression changes after drug treatments were calculated by comparing the gene expression of drug-treated tg-mel to vehicle-treated tg-mel. Log2FCs by drug were plotted as open red dots in the order of reference TDS gene expression. Solid red dots represent statistically significant (p-value < 0.05; |Log2FC| ≥ 0.6) differentially expressed genes by drug treatment between drug-treated tg-mel fish and control individuals tg-mel. Differentially expressed genes that belong to reference pathways and functions are plotted in the bar graph. Genes are grouped in functions and plotted in ascending order of Log2FC by drug treatment. (a) Of the 97 TDS genes representing the transcriptional phenotypic difference between tg-mel and wt medaka, 25 nM Trametinib altered the expression of six TDS genes, and 13 genes belonged to reference functional categories. Drug scoring calculation resulted in a TDS activation Z-score of −3.00, and a Ks_drug score of −0.9. Eight control samples consisted of five control samples from trial 1, and 3 from trial 2; five drug-treated samples consisted of two samples from trial 1 and three from trial 2. (b) 50 µM Cisplatin treatment led to differential expression of three TDS genes, and nine genes belonged to reference functional categories in tg-mel medaka. Cisplatin treatments resulted in a TDS activation Z-score of −4.01, and Ks_drug score of −1.19. Eight control samples consisted of five control samples from trial 1, and three samples from trial 2; six drug-treated samples consisted of three samples from trial 1 and three samples from trial 2.
