细胞周期检查点
细胞生物学
生物
重编程
化学
细胞周期
癌症研究
细胞
生物化学
作者
Yangyang Yuan,Chenwei Wang,Xuran Zhuang,Shaofeng Lin,Miaomiao Luo,Wankun Deng,Jiaqi Zhou,Lihui Liu,Lina Mao,Wenbo Peng,Jian Chen,Qiang-Song Wang,Yilai Shu,Yu Xue,Pengyu Huang
标识
DOI:10.1038/s41467-022-32976-9
摘要
Abstract Protein kinase-mediated phosphorylation plays a critical role in many biological processes. However, the identification of key regulatory kinases is still a great challenge. Here, we develop a trans-omics-based method, central kinase inference, to predict potentially key kinases by integrating quantitative transcriptomic and phosphoproteomic data. Using known kinases associated with anti-cancer drug resistance, the accuracy of our method denoted by the area under the curve is 5.2% to 29.5% higher than Kinase-Substrate Enrichment Analysis. We further use this method to analyze trans-omic data in hepatocyte maturation and hepatic reprogramming of human dermal fibroblasts, uncovering 5 kinases as regulators in the two processes. Further experiments reveal that a serine/threonine kinase, PIM1, promotes hepatic conversion and protects human dermal fibroblasts from reprogramming-induced ferroptosis and cell cycle arrest. This study not only reveals new regulatory kinases, but also provides a helpful method that might be extended to predict central kinases involved in other biological processes.
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