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Single-Cell Allele-Specific Gene Expression Analysis

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Computational Methods for Single-Cell Data Analysis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1935))

Abstract

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.

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Acknowledgment

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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Authors and Affiliations

  1. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA

    Meichen Dong & Yuchao Jiang

  2. Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Yuchao Jiang

  3. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    Yuchao Jiang

Authors
  1. Meichen Dong
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  2. Yuchao Jiang
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Correspondence to Yuchao Jiang .

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Editors and Affiliations

  1. Dana–Farber Cancer Institute and Harvard Chan, School of Public Health, Boston, MA, USA

    Guo-Cheng Yuan

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Dong, M., Jiang, Y. (2019). Single-Cell Allele-Specific Gene Expression Analysis. In: Yuan, GC. (eds) Computational Methods for Single-Cell Data Analysis. Methods in Molecular Biology, vol 1935. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9057-3_11

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  • DOI: https://doi.org/10.1007/978-1-4939-9057-3_11

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9056-6

  • Online ISBN: 978-1-4939-9057-3

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