Estimation of kinase activities in the time-course experiment
Kinase activities were estimated using known kinase-substrate relationships in literature (Bachman et al., 2019). The resource comprises of a comprehensive collection of phosphosite annotations of direct substrates of kinases obtained from six databases, PhosphoSitePlus, SIGNOR, HPRD, NCI-PID, Reactome, and the BEL Large Corpus, and using three text-mining tools, REACH, Sparser, and RLIMS-P. Kinase activities were inferred as a -log10(p value) of Z-test from the comparison of fold changes in phosphosite measurements of the known substrates against the overall distribution of fold changes across the sample. This statistical approach has been previously shown to perform well at estimating kinase activities (Hernandez-Armenta et al., 2017; Casado et al., 2013). We collected substrate annotations for 400 kinases with available data. Kinase activities for kinases with 3 or more measured substrates were considered leaving us with 97 kinases with activity estimates in at least one or more infection time points.