TGFβ treatment decreases the average expression of this group of genes at 24 h stronger than transporters or excretion proteins. The difference analysis in Figure 1D shows that considerable deviations only occur at the 24 h time point—longer bars occur at C6 h/24 h, T6h/24 h, and C/T 24 h. Down-regulation of the average for excretion proteins is larger than for enzymes, and is quite small for transporters. Interestingly, TGFβ treatment seems to play a minor role for excretion proteins, while
for enzymes (and for the transporters at a lower degree) the difference induced by TGFβ treatment (C/T 24 h) is larger than for comparison of time points Inhibitors,research,lifescience,medical (e.g., C6 h/24 h). The significance of these average differences is low for excretion proteins (due to their low number and their large deviations), low for transport proteins (due to the small difference), and is high only for enzymes (T6 h/24 h and C/T Inhibitors,research,lifescience,medical 24 h comparisons). 2.2. ModeScore Analysis Metabolism is represented by a modified version of HepatoNet1 Inhibitors,research,lifescience,medical [17] (see Section 4.2 and Supplementary file 2) and 987 reference functions (see Section 4.3 and Supplementary file 3) for which flux distributions have been computed using FASIMU [19], see Supplementary file 4. In the ModeScore method ([15], see also Section 4.5) a regulation amplitude for each reference flux distribution and each pair of transcript profiles is computed.
This value is compatible Inhibitors,research,lifescience,medical to the change in log2 abundances, viz. if only one gene is assigned to the flux distribution, then the score is
equal to the difference of both log2 abundances. These scores are shown in Supplementary file 5. Additionally, for each gene assigned to the flux distribution, a contribution score is computed regarding how much the gene reflects the Quisinostat cost evaluation of the flux distribution. A score of 1 is computed for those genes whose difference in abundances is equal to the flux distribution Inhibitors,research,lifescience,medical amplitude. A score of 0 is given to a difference far from the flux distribution score. For more details, see the methods section. These component scores are shown in the Supplementary file 6 in the column “Score”. For each pair of transcript profiles, the functions with the highest up-regulation or down-regulation Montelukast Sodium are inspected, and those functional units with the most remarkable pattern were selected—see Supplementary file 1 for a detailed account of this process. For a functional unit, the relevant genes with a consistent pattern (see Supplementary file 6 for all genes) have been selected for the functional interpretation as follows. 2.3. Tyrosine Degradation Three hepatic functions are closely connected—degradation of tyrosine, conversion of phenylalanine to tyrosine (consisting of a single intracellular reaction), and degradation of phenylalanine (a combination of the other two)—and thus are treated in combination.