Figure 4.

Contribution of gene expression changes of individual reactions to 3-aminotriazole (3-AT) treatment tolerance. (A) Definition of the metric used to compare the effects of gene expression changes of individual reactions. The normalized tolerance change (NTC) for reaction i was defined as the average of the changes (Δtol_+i and Δtol_-i) in the maximum 3-AT inhibition level (k_his) tolerated by S. cerevisiae in simulations where only the gene expression data (GED) of reaction i (g_i) are considered (No GED+g_i) or excluded (GED-g_i). The average was normalized by the difference in the maximum k_his (Δtol) in simulations with (GED) and without (No GED) gene expression changes for all reactions. In these simulations, k_ser→gly was varied linearly with k_his such that when k_his=1.0 then k_ser→gly=1.0 and when k_his=4.87×10^-1 then k_ser→gly=2.27×10^-2. The values k_his=1.0 and k_his=0.0 represent no inhibition and complete inhibition, respectively. (B) Top ten reactions with the larger NTC magnitude. EC denotes the Enzyme Commission number. For lumped reactions (L), only the EC number for the first step is shown. (C) Overall gene expression changes for the ten reactions shown in B.