Abstract
Phosphorylation in eukaryotic cells plays a key role in regulating cell signaling and disease progression. Despite the ability to detect thousands of phosphosites in a single experiment using high-throughput technologies, the kinases responsible for regulating these sites are largely unidentified. To solve this, we collected the quantitative data at the transcriptional, protein, and phosphorylation levels of 10 159 samples from 23 tumor datasets and 15 adjacent normal tissue datasets. Our analysis aimed to uncover the potential impact and linkage of kinase-phosphosite (KPS) pairs through experimental evidence in publications and prediction tools commonly used. We discovered that both experimentally validated and tool-predicted KPS pairs were enriched in groups where there is a significant correlation between kinase expression/phosphorylation level and the phosphorylation level of phosphosite. This suggested that a quantitative correlation could infer the KPS interconnections. Furthermore, the Spearman's correlation coefficient for these pairs were notably higher in tumor samples, indicating that these regulatory interactions are particularly pronounced in tumors. Consequently, building on the KPS correlations of different datasets as predictive features, we have developed an innovative approach that employed an oversampling method combined with and XGBoost algorithm (SMOTE-XGBoost) to predict potential kinase-specific phosphorylation sites in proteins. Moreover, the computed correlations and predictions of kinase-phosphosite interconnections were integrated into the eKPI database (https://ekpi.omicsbio.info/). In summary, our study could provide helpful information and facilitate further research on the regulatory relationship between kinases and phosphosites.