Evaluation of tools for highly variable gene discovery from single-cell RNA-seq data

Abstract Traditional RNA sequencing (RNA-seq) allows the detection of gene expression variations between two or more cell populations through differentially expressed gene (DEG) analysis. However, genes that contribute to cell-to-cell differences are not discoverable with RNA-seq because RNA-seq sam...

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Published in:Briefings in bioinformatics Vol. 20; no. 4; pp. 1583 - 1589
Main Authors: Yip, Shun H, Sham, Pak Chung, Wang, Junwen
Format: Journal Article
Language:English
Published: England Oxford University Press 19.07.2019
Oxford Publishing Limited (England)
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ISSN:1467-5463, 1477-4054, 1477-4054
Online Access:Get full text
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Summary:Abstract Traditional RNA sequencing (RNA-seq) allows the detection of gene expression variations between two or more cell populations through differentially expressed gene (DEG) analysis. However, genes that contribute to cell-to-cell differences are not discoverable with RNA-seq because RNA-seq samples are obtained from a mixture of cells. Single-cell RNA-seq (scRNA-seq) allows the detection of gene expression in each cell. With scRNA-seq, highly variable gene (HVG) discovery allows the detection of genes that contribute strongly to cell-to-cell variation within a homogeneous cell population, such as a population of embryonic stem cells. This analysis is implemented in many software packages. In this study, we compare seven HVG methods from six software packages, including BASiCS, Brennecke, scLVM, scran, scVEGs and Seurat. Our results demonstrate that reproducibility in HVG analysis requires a larger sample size than DEG analysis. Discrepancies between methods and potential issues in these tools are discussed and recommendations are made.
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ISSN:1467-5463
1477-4054
1477-4054
DOI:10.1093/bib/bby011