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A Computational Pipeline for Intergenic/Intragenic Enhancer RNA Quantification in Mouse Embryonic Stem Cells

A Computational Pipeline for Intergenic/Intragenic Enhancer RNA Quantification in Mouse Embryonic Stem Cells

Published on: October 28, 2025

scAED: a framework for mapping the enhancer state at single-cell resolution.

Avinash Veerappa¹, Jai Chand Patel¹, Sushil Shakyawar¹

¹Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, S 45th St, Omaha, NE 68198, United States.

Briefings in Bioinformatics

|December 8, 2025

Summary

This summary is machine-generated.

We developed a novel computational framework to map active enhancers in individual cells, creating the single-cell Active Enhancer Database (scAED). This database captures enhancer dynamics, crucial for understanding cellular heterogeneity and gene regulation in health and disease.

Keywords:

database enhancer multiome scAED single-cell snATACseq snRNAseq transcription factor

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Area of Science:

Genomics
Epigenetics
Computational Biology

Background:

Cellular heterogeneity arises from dynamic gene expression.
Enhancers regulate gene expression spatially and temporally.
Existing enhancer databases obscure cell-specific enhancer dynamics.

Purpose of the Study:

To develop a computational framework for single-cell enhancer activity analysis.
To create a comprehensive database of active enhancers at single-cell resolution.
To address limitations of pooled-cell and clustered single-cell data.

Main Methods:

Utilized sc-Multiome and matched snATAC-seq/snRNA-seq datasets.
Developed a novel computational framework to extract enhancer chromatin states per cell.
Established the single-cell Active Enhancer Database (scAED).

Main Results:

Catalogued over 2.2 million unique active enhancer regions across diverse cell types.
scAED provides single-cell resolution of enhancer activity.
Introduced novel features like bidirectional enhancer characterization and trans-acting element capture.

Conclusions:

scAED offers unprecedented insights into enhancer dynamics and cellular heterogeneity.
The database facilitates hypothesis generation for regulatory mechanisms in health and disease.
scAED is a growing resource for enhancer biology research.