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Xtalk: a path-based approach for identifying crosstalk between signaling pathways.

Allison N Tegge1, Nicholas Sharp2, T M Murali3

  • 1Department of Computer Science, Department of Statistics and.

Bioinformatics (Oxford, England)
|September 25, 2015
PubMed
Summary
This summary is machine-generated.

We developed Xtalk, a novel computational method to identify crosstalk between cell signaling pathways. Xtalk improves accuracy in detecting pathway interactions by analyzing path lengths, outperforming existing methods.

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Area of Science:

  • Computational Biology
  • Systems Biology
  • Bioinformatics

Background:

  • Cellular communication relies on signal transduction pathways.
  • Pathway crosstalk, where one pathway affects another, is a complex biological phenomenon.
  • Existing computational methods for identifying crosstalk are limited by simple overlap statistics.

Purpose of the Study:

  • To present Xtalk, a new path-based computational approach for discovering crosstalk between signaling pathways.
  • To improve the accuracy and mechanistic understanding of identified pathway crosstalk.
  • To provide a robust tool for analyzing large-scale pathway interaction networks.

Main Methods:

  • Xtalk computes the statistical significance of average path lengths connecting receptors in one pathway to transcription factors in another.
  • The approach is designed to report precise interactions and mechanisms supporting crosstalk.
  • Xtalk was applied to signaling pathways within the KEGG and NCI-PID databases.

Main Results:

  • Xtalk achieved an AUC of 0.65 on a manually curated gold standard dataset, a 12% improvement over competing methods.
  • The method demonstrated high literature support for top-ranked crosstalking pathway pairs (81% in KEGG, 78% in NCI-PID).
  • Xtalk successfully recovered known crosstalk mechanisms through network analysis.

Conclusions:

  • Xtalk offers a significant advancement in identifying and understanding pathway crosstalk.
  • Evaluating crosstalk on a pathway-by-pathway basis is crucial for accurate analysis.
  • The Xtalk software and identified crosstalk networks are publicly available.