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PathwayVote: an R package for robust pathway enrichment analysis for DNA methylation data using a consensus-based

Yinan Zheng1, Feng Gao2, Lifang Hou1

  • 1Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States.

Bioinformatics (Oxford, England)
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Summary

Pathway enrichment analysis for epigenomewide association studies is improved by PathwayVote. This R package uses expression quantitative trait methylation data to identify robust pathways, reducing arbitrary cutoffs and enhancing reproducibility.

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Area of Science:

  • Genomics
  • Epigenetics
  • Bioinformatics

Background:

  • Pathway enrichment analysis is crucial for interpreting epigenomewide association studies (EWAS).
  • Conventional methods often use arbitrary thresholds and simplified CpG-gene mappings, limiting their effectiveness.
  • Expression quantitative trait methylation (eQTM) data offers potential for improved CpG-gene mapping but is underutilized.

Purpose of the Study:

  • To develop a novel R package, PathwayVote, for robust pathway enrichment analysis.
  • To leverage eQTM data for more accurate CpG-gene relationship mapping in EWAS.
  • To reduce reliance on arbitrary cutoffs and enhance the sensitivity and reproducibility of enrichment results.

Main Methods:

  • Developed PathwayVote, an R package implementing a voting-based consensus approach.
  • Integrated eQTM data to refine CpG-gene mappings.
  • Applied the package to identify robustly enriched pathways.

Main Results:

  • PathwayVote successfully identifies robustly enriched pathways.
  • The voting-based consensus approach reduces dependence on arbitrary cutoffs.
  • The package improves the sensitivity and reproducibility of enrichment findings.

Conclusions:

  • PathwayVote offers a more reliable method for pathway enrichment analysis in EWAS.
  • Utilizing eQTM data significantly enhances the interpretation of methylation data.
  • The R package provides a valuable tool for the genomics and epigenetics research community.