miREA: a network-based tool for edge-based microRNA-oriented enrichment analysis

We present miRNA-oriented Enrichment Analysis (miREA) framework, which integrates miRNA-gene interaction (MGI) networks with miRNA and gene transcriptomic data to improve functional interpretation of miRNAs.

miREA is designed to address the intrinsic many-to-many regulatory interactions of MGIs and reduce biases introduced by conventional node-centric enrichment approaches, by explicitly modeling miRNA-gene regulatory networks, pathway topology, and expression-informed MGI edge scores.

Workflow

Key Features

miREA leverages MGI for network-based pathway enrichment analysis.
miREA designs MGI scores to characterize regulatory strengths of MGIs.
miREA implements four node-based methods and five edge-based methods, spanning over-representation, scoring-based, topology-aware, and network propagation approaches.
The edge-based methods outperform node-based methods in sensitivity and biological interpretability.
miREA elucidates miRNA-gene-pathway regulatory mechanisms in bladder cancer.

Installation

if (!requireNamespace("BiocManager", quietly = TRUE))
    install.packages("BiocManager")
BiocManager::install("miREA")

To install the development version directly from GitHub:

if (!requireNamespace("BiocManager", quietly = TRUE))
    install.packages("BiocManager")
BiocManager::install("laixn/miREA")

Usage

See vignette("miREA") for a full worked example using the small example dataset bundled with the package (?miREA_example_data), covering the full workflow: getAllInputData() → miREA() → plotSummary()/plotHeatmap()/plotHeatmapSankey().

library(miREA)
vignette("miREA", package = "miREA")

Every exported function also has a runnable example on its own help page, e.g. ?Edge_ORA, ?Edge_Topology.

Output

miREA returns results containing:

a list named input_data for the input data of miREA.
a list named result for the enrichment result, including parameters, valid methods, time for different methods, and a data.frame for each method.
visualization plots for methods comparison, and heatmap/Sankey plots for each edge-based method to explore the miRNA-gene-pathway regulatory mechanisms discovered.

All raw data, processed data, and original results for the various cancer types and pathway sets used in the miREA manuscript have been deposited at .

Citation

Zhesi Zhang, Xin Lai. miREA: a network-based tool for microRNA-oriented enrichment analysis. Submitted (2026).

@article{Zhang_miREA_2026,
  title={miREA: a network-based tool for microRNA-oriented enrichment analysis},
  author={Zhesi Zhang, Xin Lai},
  journal={bioRxiv},
  doi={10.64898/2026.02.27.708509},
  year={2026}}