Supplementary Figure 8: Experimental validation of kinase-substrate rewiring. | Nature Methods

Supplementary Figure 8: Experimental validation of kinase-substrate rewiring.

From: MIMP: predicting the impact of mutations on kinase-substrate phosphorylation

Supplementary Figure 8

Nine experimentally validated (a) loss and (b) gain-of-phosphorylation events. Five network-rewiring mutations were selected as top ranking in terms of the patient sample count. For each of mutation, we selected top-ranking kinases rewired by that mutation in terms of the log ratio between wild type and mutant MSS scores. The bar plots quantify in vitro kinase activity in replicates of two for wild type and mutant peptide sequences as well as negative controls (blank). P-values represent the significance of difference between the wild type and mutant kinase activity, computed using an empirical Bayes moderated t-test and corrected for multiple testing using the Benjamini-Hochberg method of False Discovery Rate. The last four rewiring events were assayed against close family members of the rewired kinase instead of the exact kinase for further experimental support.

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