Repository logo
 

Mosaic autosomal aneuploidies are detectable from single-cell RNAseq data.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Griffiths, Jonathan A 
Scialdone, Antonio 

Abstract

BACKGROUND: Aneuploidies are copy number variants that affect entire chromosomes. They are seen commonly in cancer, embryonic stem cells, human embryos, and in various trisomic diseases. Aneuploidies frequently affect only a subset of cells in a sample; this is known as "mosaic" aneuploidy. A cell that harbours an aneuploidy exhibits disrupted gene expression patterns which can alter its behaviour. However, detection of aneuploidies using conventional single-cell DNA-sequencing protocols is slow and expensive. METHODS: We have developed a method that uses chromosome-wide expression imbalances to identify aneuploidies from single-cell RNA-seq data. The method provides quantitative aneuploidy calls, and is integrated into an R software package available on GitHub and as an Additional file of this manuscript. RESULTS: We validate our approach using data with known copy number, identifying the vast majority of aneuploidies with a low rate of false discovery. We show further support for the method's efficacy by exploiting allele-specific gene expression levels, and differential expression analyses. CONCLUSIONS: The method is quick and easy to apply, straightforward to interpret, and represents a substantial cost saving compared to single-cell genome sequencing techniques. However, the method is less well suited to data where gene expression is highly variable. The results obtained from the method can be used to investigate the consequences of aneuploidy itself, or to exclude aneuploidy-affected expression values from conventional scRNA-seq data analysis.

Description

Keywords

Aneuploidy detection, Copy-number, RNAseq, Single-cell, Alleles, Aneuploidy, Animals, Cell Line, DNA Copy Number Variations, False Positive Reactions, Gene Expression, Gene Expression Profiling, Mice, Mosaicism, Sequence Analysis, RNA, Single-Cell Analysis

Journal Title

BMC Genomics

Conference Name

Journal ISSN

1471-2164
1471-2164

Volume Title

18

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (109081/Z/15/Z)