Fig. 3
Kinase profiling and elastic net regression successfully predict known and novel host kinases important for regulating P. yoelii LS infection. a Venn diagram depicting overlap between predicted kinase hits and kinases previously reported by whole-kinome siRNA screen. Our approach predicted 47 host kinases to be regulators of Plasmodium LS infection. Kinases without any previously described role in LS infection are depicted in blue. Kinases previously implicated in LS infection, and also predicted by the elastic net regression at α = 0.8, are depicted in red. Of the kinases previously demonstrated to regulate Plasmodium LS infection, those which are predicted at α < 0.8 are depicted in yellow. Kinases not recapitulated by our approach at any value of α are shown below. Statistical comparison to existing data was performed using hypergeometric probability test (p = 0.01). b Bar graph depicting LS development in cells with shRNA-mediated knockdown of a subset of predicted kinases. Values are normalized to non-treated parasites which are indicated by solid line. Green dashed line represents LS burden ≤70% of control. Predicted kinases with previous reports of LS activity are depicted in red. Novel predicted kinases are depicted in blue. Data is representative of at least three independent experiments. Error bars represent standard deviation of technical replicates. c Functional enrichment analysis of predicted kinases. The 47 predicted host kinases were analyzed using DAVID Bioinformatics Resources 6.825,26. The 300 kinases that are evaluated by this approach were set as the background for the analysis. P-values were determined by modified Fisher’s exact test
