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Related Experiment Video

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Multiplexed Single Cell mRNA Sequencing Analysis of Mouse Embryonic Cells
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SCALE: modeling allele-specific gene expression by single-cell RNA sequencing.

Yuchao Jiang1, Nancy R Zhang2, Mingyao Li3

  • 1Genomics and Computational Biology Graduate Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Genome Biology
|April 28, 2017
PubMed
Summary
This summary is machine-generated.

We developed SCALE to analyze allele-specific gene expression bursting at the single-cell level. This method reveals that gene expression differences between alleles are primarily driven by variations in burst frequency.

Keywords:
Allele-specific expressionExpression stochasticitySingle-cell RNA sequencingTechnical variabilityTranscriptional burstingcis and trans transcriptional control

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Traditional bulk RNA sequencing averages gene expression, masking allele-specific dynamics.
  • Single-cell RNA sequencing enables the study of allele-specific expression and bursting.
  • Understanding allele-specific bursting is crucial for deciphering gene regulation.

Purpose of the Study:

  • To introduce SCALE, a novel computational method for analyzing genome-wide allele-specific bursting.
  • To account for technical variability in single-cell RNA sequencing data.
  • To identify genes with allelic differences in bursting parameters and non-independent allelic bursting.

Main Methods:

  • Development and application of the SCALE (Single-cell Allele-specific Expression) analysis tool.
  • Analysis of allele-specific bursting parameters, including burst frequency and burst size.
  • Adjustment for technical noise in single-cell RNA sequencing data.

Main Results:

  • SCALE effectively analyzes genome-wide allele-specific bursting.
  • Identification of genes exhibiting significant allelic differences in bursting parameters.
  • Discovery that cis-regulatory control predominantly influences allele-specific burst frequency.

Conclusions:

  • SCALE provides a robust framework for studying allele-specific gene expression bursting.
  • Allele-specific differences in gene expression are largely determined by burst frequency.
  • The findings offer new insights into the mechanisms of gene regulation at the allelic level.