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Related Experiment Video

Updated: Jan 17, 2026

Rare Event Detection Using Error-corrected DNA and RNA Sequencing

Rare Event Detection Using Error-corrected DNA and RNA Sequencing

Published on: August 3, 2018

ASPEN: Robust detection of allelic dynamics in single cell RNA-seq.

Veronika Petrova^1,2, Muqing Niu^1,2, Thomas Vierbuchen^3,4

¹Victor Chang Cardiac Research Institute, Sydney 2010, Australia.

Biorxiv : the Preprint Server for Biology

|September 15, 2025

Summary

We developed ASPEN, a new method for analyzing single-cell RNA sequencing data in F1 hybrids. ASPEN accurately models allelic expression and variance, improving the study of gene regulation and cellular processes.

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Area of Science:

Genomics
Computational Biology
Molecular Biology

Background:

Single-cell RNA sequencing (scRNA-seq) of F1 hybrids offers insights into gene regulation.
Technical noise in scRNA-seq limits accurate allelic measurements.
Distinguishing true allelic imbalance from noise is challenging.

Purpose of the Study:

To introduce ASPEN, a statistical method for modeling allelic mean and variance in scRNA-seq data from F1 hybrids.
To improve the analysis of allelic expression and variance in single cells.
To enhance the understanding of gene regulatory mechanisms in F1 hybrid systems.

Main Methods:

ASPEN employs a sensitive mapping pipeline and adaptive shrinkage techniques.
The method models both allelic mean and variance.
Simulations were performed using sparse droplet-based scRNA-seq data.

Main Results:

ASPEN shows improved sensitivity and false discovery control compared to existing methods.
The method successfully identified genes with incomplete X inactivation and stochastic monoallelic expression.
Analysis revealed reduced variance in essential cellular pathways and increased variance in neurodevelopmental and immune genes.

Conclusions:

ASPEN provides a robust framework for dissecting allelic regulatory phenomena in F1 hybrid scRNA-seq data.
The method enhances the ability to detect subtle allelic expression differences and variance.
Findings highlight the role of allelic variance in key biological processes, including development and immunity.