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Characterizing noise structure in single-cell RNA-seq distinguishes genuine from technical stochastic allelic expression.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Kim, Jong Kyoung 
Kolodziejczyk, Aleksandra A 
Ilicic, Tomislav 
Teichmann, Sarah A 
Marioni, John C 

Abstract

Single-cell RNA-sequencing (scRNA-seq) facilitates identification of new cell types and gene regulatory networks as well as dissection of the kinetics of gene expression and patterns of allele-specific expression. However, to facilitate such analyses, separating biological variability from the high level of technical noise that affects scRNA-seq protocols is vital. Here we describe and validate a generative statistical model that accurately quantifies technical noise with the help of external RNA spike-ins. Applying our approach to investigate stochastic allele-specific expression in individual cells, we demonstrate that a large fraction of stochastic allele-specific expression can be explained by technical noise, especially for lowly and moderately expressed genes: we predict that only 17.8% of stochastic allele-specific expression patterns are attributable to biological noise with the remainder due to technical noise.

Description

Keywords

Alleles, Animals, Artifacts, Gene Expression Profiling, Gene Regulatory Networks, Mice, Mouse Embryonic Stem Cells, RNA, Sequence Analysis, RNA, Single-Cell Analysis, Stochastic Processes

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

6

Publisher

Springer Science and Business Media LLC