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Identification of Kinase-substrate Pairs Using High Throughput Screening
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Robust inference of kinase activity using functional networks.

Serhan Yılmaz1, Marzieh Ayati2, Daniela Schlatzer3

  • 1Department of Computer and Data Sciences, Case Western Reserve University, Cleveland, OH, USA. serhan.yilmaz@case.edu.

Nature Communications
|February 20, 2021
PubMed
Summary
This summary is machine-generated.

We developed RoKAI, a network-based tool that improves kinase activity inference from phosphoproteomic data. This method enhances disease-related kinase identification for targeted therapies.

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Area of Science:

  • Biochemistry
  • Systems Biology
  • Bioinformatics

Background:

  • Mass spectrometry is key for high-throughput phosphoproteomic analysis.
  • Phosphoproteomic data aids in inferring kinase activity, crucial for understanding diseases like cancer and neurodegenerative disorders.
  • Current methods for kinase activity inference can be limited by data completeness and integration of functional information.

Purpose of the Study:

  • To present RoKAI, a network-based framework to enhance kinase activity inference.
  • To integrate diverse functional information for a more robust analysis of signaling pathways.
  • To improve the identification of dysregulated kinases in disease contexts.

Main Methods:

  • Developed RoKAI, a network-based computational framework.
  • Integrated multiple sources of functional information to capture coordinated signaling changes.
  • Utilized computational experiments to validate the framework's performance.

Main Results:

  • Phosphorylation sites within a kinase's functional neighborhood significantly predict its activity.
  • RoKAI consistently improves the accuracy and robustness of kinase activity inference methods.
  • The framework is effective even with missing data annotations and quantifications.

Conclusions:

  • RoKAI enhances the reliability of kinase activity inference from phosphoproteomic data.
  • This approach facilitates the identification of understudied kinases implicated in diseases.
  • RoKAI holds potential for developing novel kinase inhibitors for targeted therapeutic strategies.