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

## TL;DR

PathwayVote is an R package that improves DNA methylation pathway analysis by using a voting system and eQTM data for better accuracy and reliability.

## Contribution

PathwayVote introduces a voting-based consensus framework and integrates eQTM data to enhance pathway enrichment analysis for DNA methylation.

## Key findings

- PathwayVote reduces reliance on arbitrary thresholds in pathway analysis.
- The package improves sensitivity and reproducibility of enrichment results using eQTM data.
- PathwayVote is available on GitHub and CRAN for public use.

## Abstract

Pathway enrichment analysis is commonly used to interpret epigenomewide association studies, yet conventional methods often rely on arbitrary thresholds and simplified CpG–gene mappings, making them sensitive to analytical choices and unable to fully leverage CpG–gene relationships Recent advances in expression quantitative trait methylation (eQTM) studies offer a rich resource to refine these mappings, but are rarely utilized in DNA methylation enrichment pipelines.

We developed PathwayVote, an R package that implements a voting-based consensus approach and leverages eQTM data to identify robustly enriched pathways. PathwayVote reduces dependence on arbitrary cutoffs and improves sensitivity and reproducibility of enrichment results.

PathwayVote is freely available on GitHub (https://github.com/YinanZheng/PathwayVote) under the GPL-3 license and CRAN: https://CRAN.R-project.org/package=PathwayVote. The version of the code corresponding to this manuscript has been archived on Zenodo (https://doi.org/10.5281/zenodo.17209507).