Document Type
Article
Publication Date
2-19-2021
Abstract
Mass spectrometry enables high-throughput screening of phosphoproteins across a broad range of biological contexts. When complemented by computational algorithms, phospho-proteomic data allows the inference of kinase activity, facilitating the identification of dysregulated kinases in various diseases including cancer, Alzheimer’s disease and Parkinson’s disease. To enhance the reliability of kinase activity inference, we present a network-based framework, RoKAI, that integrates various sources of functional information to capture coordinated changes in signaling. Through computational experiments, we show that phosphorylation of sites in the functional neighborhood of a kinase are significantly predictive of its activity. The incorporation of this knowledge in RoKAI consistently enhances the accuracy of kinase activity inference methods while making them more robust to missing annotations and quantifications. This enables the identification of understudied kinases and will likely lead to the development of novel kinase inhibitors for targeted therapy of many diseases. RoKAI is available as web-based tool at http://rokai.io.
Keywords
cellular signalling networks, computational models, data mining, phosphorylation, software
Publication Title
Nature Communications
Rights
© The Author(s) 2021
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Yılmaz, S., Ayati, M., Schlatzer, D. et al. Robust inference of kinase activity using functional networks. Nat Commun 12, 1177 (2021). https://doi.org/10.1038/s41467-021-21211-6