Fig. 6
Metabolic rewiring by KDAC inhibitors predicts variation in sensitivity between these inhibitors among cancer cell lines. a Overview of the analysis comparing the sensitivity of CCLE cell lines to four KDAC inhibitors—vorinostat, panobinostat, belinostat, and entinostat. The acetylation flux in each cell line corresponding to each drug treatment was determined by FBA by accounting for both the basal transcriptomic profiles of each cell line and the metabolic impact of these drugs. Cell line-drug combinations were grouped into two classes—the first group of cell line-drug pairs did not show any significant difference in acetylation flux compared to the other drugs, while the second class showed large differences. b The histogram and box plots show the distribution of normalized sensitivity scores of the four drugs among the two cell line groups. The experimental sensitivity data was median normalized so that a score of 0 implies that there was no difference in sensitivity between the drugs while a negative score implies greater sensitivity for a drug relative to other three drugs. The normalized sensitivity scores were significantly lower for the group that showed large difference in acetylation flux between the drugs compared to the group that showed no acetylation flux difference (p value = 2 × 10− 62, t-test)