Faculty, Staff and Student Publications
Publication Date
9-6-2022
Journal
Nature Communications
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.
Keywords
Cell Cycle, Cell Cycle Checkpoints, Drug Resistance, Neoplasm, Ferroptosis, Humans, Phosphorylation, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins c-pim-1
DOI
10.1038/s41467-022-32976-9
PMID
36068222
PMCID
PMC9448736
PubMedCentral® Posted Date
September 2022
PubMedCentral® Full Text Version
Post-Print
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Medical Cell Biology Commons
Comments
Supplementary Materials