Fig. 1: Schematic diagram of the CKI algorithm.

First, the transcriptomes and phosphoproteomes of control and treated samples in a defined biological process were quantified by RNA-seq and TMT-based LC-MS/MS technology. Bowtie53, TopHat54, and Cufflinks55 were used to process the transcriptomic data, then Cuffdiff in Cufflinks55 or edgeR49 was used to identify differentially expressed mRNAs (DEMs) and map differentially expressed protein kinases (DEPKs). We developed an intensity-based method and a network-based method to identify differentially altered PKs using the phosphoproteomic data. These three types of data were then combined to synergistically predict potentially central PKs in regulating a defined biological process.