KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data

Sam Crowl, Ben T. Jordan, Hamza Ahmed, Cynthia X. Ma and Kristen M. Naegle ()
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Sam Crowl: University of Virginia, Department of Biomedical Engineering and the Center for Public Health Genomics
Ben T. Jordan: University of Virginia, Department of Biomedical Engineering and the Center for Public Health Genomics
Hamza Ahmed: University of Virginia, Department of Biomedical Engineering and the Center for Public Health Genomics
Cynthia X. Ma: Washington University in St. Louis
Kristen M. Naegle: University of Virginia, Department of Biomedical Engineering and the Center for Public Health Genomics

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Kinase inhibitors as targeted therapies have played an important role in improving cancer outcomes. However, there are still considerable challenges, such as resistance, non-response, patient stratification, polypharmacology, and identifying combination therapy where understanding a tumor kinase activity profile could be transformative. Here, we develop a graph- and statistics-based algorithm, called KSTAR, to convert phosphoproteomic measurements of cells and tissues into a kinase activity score that is generalizable and useful for clinical pipelines, requiring no quantification of the phosphorylation sites. In this work, we demonstrate that KSTAR reliably captures expected kinase activity differences across different tissues and stimulation contexts, allows for the direct comparison of samples from independent experiments, and is robust across a wide range of dataset sizes. Finally, we apply KSTAR to clinical breast cancer phosphoproteomic data and find that there is potential for kinase activity inference from KSTAR to complement the current clinical diagnosis of HER2 status in breast cancer patients.

Date: 2022
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DOI: 10.1038/s41467-022-32017-5

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