Figure 1.
This figure is a schematic workflow of our method for GSMM construction.
The significant down-regulated gene (p-value <0.01) and the corresponding reactions (according to GPR) were determined. (In this model, 5 genes and 6 reactions were identified). Afterward, we have restricted the fluxes of the given reactions according to their fold change values. For example if the fold change value is −2, we have restricted the upper bound and lower bound of the corresponding flux to one quarter of the corresponding WT.
Figure 2.
Shows the workflow of our study.
This study consists of two parts; topological analysis and constraint-based modeling. In the topological analysis section, we used the twelve centrality indices of the undirected enzyme-centric network of yeast and examined the distribution of the down-regulated genes in the nine mutated histone tails profiles, extracted from geWorkbench software. In the constraint-based modeling section, we integrated gene expression of nine groups of the mutated histone tails profiles to the yeast GSMM and constructed new models. FBA, FVA, pFBA and Single gene deletion analyzed by COBRA toolbox.
Table 1.
Up and down significant metabolic genes in each group.
Figure 3.
Shows the distribution of down-regulated enzymes in enzyme-centric network of yeast in H4 substituted tail model.
The x- and y-axis indicate the centrality score and the enzyme ID of the H4 substituted tail model, respectively.
Figure 4.
Shows the growth rate (the optimal objective value) of all constructed GSMMs calculated by FBA.
The unit of the growth rate is mmol gDW−1 hr−1 (milimoles per gram dry cell weight per hour).
Figure 5.
Comparison of the number of all, positive and negative carrying-flux reactions (blue, brown and green bars, respectively) in all constructed GSMMs.
Table 2.
Increased flux range of yeast metablic subnetwork in the 9 mutated histone tail models.
Table 3.
Decreased flux range of yeast metablic subnetwork in the 9 mutated histone tail models.
Table 4.
The percentage of the lowly expressed enzymes of nine constructed models in each category of pFBA and Single Gene Deletion.
Table 5.
We set the objective function of the constructed models to the given reactions (acetyl-CoA synthetase and acetyl-CoA carboxylase reactions) and turned the lower bound to zero for maximizing the production and regulation reaction of acetyl-CoA.