Fig. 4

Kinome reprogramming in severe COVID-19. A Heatmap of significantly differentially expressed protein kinases between the patient and HC groups. B Differentially phosphorylated sites on Tyr kinases. C Differentially phosphorylated sites on Ser/Thr kinases. For A–C, p < 0.1 between HC and at least one of the patient groups, Student’s t-test. D Kinase activity prediction using Kinase-Substrate Enrichment Analysis (KSEA). The phosphoproteome data were used to predict which kinases may be activated or supressed in the COVID-19 PBMCs compared to healthy controls, based on enrichment of phosphorylated substrates in the COV samples. The prediction employed both the PhosphositePlus and NetworKIN datasets. Kinases with z > 1.5 or z < -1.5 are shown. “AL”: kinase activation loop, “activating”: the phosphorylation induces kinase activity, “inhibitory”: the phosphorylation inhibits kinase activity. The annotations are based on the PhosphositePlus database.