Figure 4: Modelling the effect of mTOR inhibition.
From: Large-scale models of signal propagation in human cells derived from discovery phosphoproteomic data
(a) Fifteen sites perturbed under one of the two mTOR inhibitors in our data were connected to mTOR in three independent optimizations, using exclusively experimentally demonstrated interactions. Results of these were combined into average frequencies in final populations of models, which were used to extract a best-consensus model with 20% tolerance around the highest frequency edges. This model recapitulates effects on known substrates of mTOR, and highlights a good agreement between the effects of the two inhibitors. (b) Sites that were found to be perturbed but did not have an experimentally demonstrated kinase were connected to the optimized network based on predictions from networKIN. (c) Predictions were prioritized based on the sign of the perturbations observed, and functional annotations of proteins were extracted from Uniprot. This representation allows to analyse such data in a way that directly traces the effect of a kinase inhibition on the phosphoproteome, and prioritizes predicted kinases.
