# Tracing regulatory element networks using epigenetic traits to identify key transcription factors: TENET R/Bioconductor package

**Authors:** Daniel J Mullen, Zexun Wu, Ethan Nelson-Moore, Huan Cao, Lauren Han, Ite A Offringa, Suhn K Rhie

PMC · DOI: 10.1093/bioinformatics/btaf435 · Bioinformatics · 2025-08-01

## TL;DR

TENET is a new R package that helps researchers identify key transcription factors and regulatory elements in specific cell types using epigenetic data.

## Contribution

The TENET package introduces a novel method to trace regulatory element networks using epigenetic traits across diverse cell types and cancer data.

## Key findings

- TENET integrates histone marks, open chromatin, DNA methylation, and gene expression data to identify cell type-specific TFs and REs.
- The package includes methods to analyze findings with motifs, clinical data, and chromatin conformation datasets.
- TENET was applied to pan-cancer data, revealing TFs and REs linked to ten cancer types.

## Abstract

There is a lack of publicly available bioinformatic tools that can be widely used by researchers to identify transcription factors (TFs) that regulate cell type-specific regulatory elements (REs). To address this, we developed the Tracing regulatory Element Networks using Epigenetic Traits (TENET) R/Bioconductor package. By collecting hundreds of histone mark and open chromatin datasets from a variety of cell lines, primary cells, and tissues, and comparing these features along with matched DNA methylation and gene expression data, TENET identifies TFs and REs linked to a specific cell type. Moreover, we developed methods to interrogate findings using motifs, clinical information, and other genomic and chromatin conformation capture datasets, and applied them to pan-cancer data, highlighting TFs and REs associated with ten different cancer types. TENET enables researchers to better characterize the 3D epigenomes of cell types of interest for future clinical applications.

TENET is available at http://bioconductor.org/packages/TENET. Curated functional genomic datasets utilized by TENET are available at http://bioconductor.org/packages/TENET.AnnotationHub. Example datasets are available at http://bioconductor.org/packages/TENET.ExperimentHub.

## Full-text entities

- **Diseases:** cancer (MESH:D009369)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12349384/full.md

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12349384/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12349384/full.md

---
Source: https://tomesphere.com/paper/PMC12349384