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High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
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ctPath: Demixing pathway crosstalk effect from transcriptomics data for differential pathway identification.

Xin-Ping Xie1, Bin Gan2, Wulin Yang3

  • 1School of Mathematics and Physics, Anhui Jianzhu University, Hefei, Anhui, China.

Journal of Biomedical Informatics
|July 31, 2017
PubMed
Summary
This summary is machine-generated.

This study introduces ctPath, a novel method for identifying differentially expressed pathways (DEPs) in transcriptomics data. CtPath accounts for pathway crosstalk, improving the robust detection of DEPs and correcting pathway annotation errors.

Keywords:
CancerDifferential pathwaysGene expressionNon-negative matrix factorization

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • Identifying differentially expressed pathways (DEPs) is crucial for understanding disease mechanisms and developing treatments.
  • Gene expression data is complex and noisy, making robust pathway analysis challenging.
  • Pathway crosstalk, where different biological pathways interact, is often overlooked in traditional analysis.

Purpose of the Study:

  • To develop a novel method, ctPath, for identifying DEPs by explicitly modeling pathway crosstalk.
  • To improve the accuracy and robustness of DEP identification from high-dimensional transcriptomics data.
  • To address limitations in current pathway analysis, including noise and inaccurate pathway annotations.

Main Methods:

  • Proposed a pathway crosstalk-based transcriptomics data analysis method (ctPath).
  • Modeled gene expression as a sparse non-negative linear combination of hidden pathway signals.
  • Mapped high-dimensional transcriptomics data to a low-dimensional pathway space to capture pathway activity and crosstalk effects.

Main Results:

  • CtPath effectively identifies DEPs by removing pathway crosstalk effects.
  • The method demonstrates superior performance compared to existing approaches on both simulated and real cancer data.
  • CtPath can correct incomplete and inaccurate pathway annotations found in public databases.

Conclusions:

  • CtPath offers a robust and accurate approach for identifying differentially expressed pathways.
  • The method enhances our understanding of tumor etiology and aids in clinical cancer treatment by revealing pathway activities.
  • CtPath provides a valuable tool for transcriptomics data analysis, with R code available for non-commercial use.