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eXpression2Kinases (X2K) Web: linking expression signatures to upstream cell signaling networks
Daniel J B Clarke1, Maxim V Kuleshov1, Brian M Schilder1
1DBD2K-LINCS Data Coordination and Integration Center; Knowledge Management Center for the Illuminating the Druggable Genome; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA.
eXpression2Kinases (X2K) Web predicts cell signaling pathway activity from gene expression data. This tool enhances understanding of gene regulation by identifying transcription factors and kinases involved in cellular processes.
Area of Science:
- Computational biology
- Molecular biology
- Bioinformatics
Background:
- Measuring global mRNA expression is feasible, but profiling cell signaling pathway activity remains challenging.
- Existing methods struggle to link gene expression changes to upstream signaling events.
- Understanding signaling pathway dynamics is crucial for deciphering cellular responses.
Purpose of the Study:
- To introduce X2K Web, an enhanced implementation of the eXpression2Kinases algorithm.
- To provide a user-friendly platform for predicting upstream cell signaling pathways from gene expression signatures.
- To facilitate the analysis of kinase and transcription factor involvement in biological processes.
Main Methods:
- X2K Web computationally predicts upstream signaling pathways by analyzing differentially expressed genes.
- It identifies enriched transcription factors regulating gene expression.
- It constructs subnetworks using protein-protein interactions and performs kinase enrichment analysis.
Main Results:
- X2K Web integrates extensive transcription factor, kinase, and protein-protein interaction libraries.
- It offers direct access to thousands of gene expression signatures from kinase inhibitor studies in breast cancer cell lines.
- Results are visualized as interactive network images and downloadable bar graphs.
Conclusions:
- X2K Web provides an enhanced and accessible tool for predicting cell signaling pathway activity.
- The platform aids in understanding the regulatory mechanisms underlying gene expression changes.
- Optimized default parameters ensure robust and reliable predictions for biological research.
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