Single-Cell Allele-Specific Gene Expression Analysis

  • Meichen Dong
  • Yuchao JiangEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1935)


Allele-specific expression is traditionally studied by bulk RNA sequencing, which measures average gene expression across cells. Single-cell RNA sequencing (scRNA-seq) allows the comparison of expression distribution between the two alleles of a diploid organism, and characterization of allele-specific bursting. Here we describe SCALE, a bioinformatic and statistical framework for allele-specific gene expression analysis by scRNA-seq. SCALE estimates genome-wide bursting kinetics at the allelic level while accounting for technical bias and other complicating factors such as cell size. SCALE detects genes with significantly different bursting kinetics between the two alleles, as well as genes where the two alleles exhibit non-independent bursting processes. Here, we illustrate SCALE on a mouse blastocyst single-cell dataset with step-by-step demonstration from the upstream bioinformatic processing to the downstream biological interpretation of SCALE’s output.

Key words

Single-cell RNA sequencing Allele-specific expression Transcriptional bursting Technical variability 



This work was supported by NIH grant CA142538 and a developmental award from the UNC Lineberger Comprehensive Cancer Center 2017T109 (to YJ). We thank Dr. Nancy R Zhang and Dr. Mingyao Li for helpful comments and suggestions.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biostatistics, Gillings School of Global Public HealthUniversity of North CarolinaChapel HillUSA
  2. 2.Department of Genetics, School of MedicineUniversity of North CarolinaChapel HillUSA
  3. 3.Lineberger Comprehensive Cancer CenterUniversity of North CarolinaChapel HillUSA

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