Figure 5

Refinement of the leucine biosynthesis model. (a) The refined regulatory logic suggested by MetaReg for LEU2 and LEU9. The regulators of both genes are the transcription factors Gcn4 and Leu3. For each logic, the two columns on the left represent all possible combinations of the regulators' states and the rightmost column is the regulatee's level, colored by an expression scale. Light gray background indicates that the output level predicted for the input combination is not statistically significant. (b) Predictions and measurements under specific conditions. MetaReg computes a refined logic based on the regulators' predicted activity level and the observed mRNA level of the regulated gene. As an example, the figure shows the predicted levels of Gcn4 and Leu3 in four conditions along with the measured (top strip) levels of LEU2. The corresponding predicted levels of LEU2 (bottom strip) match the logic suggested by MetaReg for LEU2, as shown in (a). (c) Discrepancy matrices for LEU2 and LEU9 before refinement (LEU9 with a constant level; LEU2 activated by Leu3 only) and after refinement (using the logics that appear in (a)). Clearly, the automatic refinement process reduces the disagreement between the model and the measurements.