2019
DOI: 10.1101/2019.12.19.883256
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Coverage-dependent bias creates the appearance of binary splicing in single cells

Abstract: Single cell RNA sequencing provides powerful insight into the factors that determine each cell's unique identity, including variation in transcription and RNA splicing among diverse cell types. Previous studies led to the surprising observation that alternative splicing outcomes among single cells are highly variable and follow a bimodal pattern: a given cell consistently produces either one or the other isoform for a particular splicing choice, with few cells producing both isoforms.Here we show that this pat… Show more

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Cited by 15 publications
(38 citation statements)
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“…For transcriptomic applications such as single cell profiling that rely on maximising the read count from minimal amounts of RNA, short read RNA sequencing can provide an advantage as a greater number of molecules can be detected at the same sequencing depth 47 . However, using short reads prevents the analysis of gene isoforms at single cell resolution 48,49 . Studies which combined long read the cell numbers for these studies are limited compared to short read RNA-Seq, an increased throughput can potentially enable the profiling of individual isoforms in thousands of cells with long read RNA-Seq.…”
Section: Discussionmentioning
confidence: 99%
“…For transcriptomic applications such as single cell profiling that rely on maximising the read count from minimal amounts of RNA, short read RNA sequencing can provide an advantage as a greater number of molecules can be detected at the same sequencing depth 47 . However, using short reads prevents the analysis of gene isoforms at single cell resolution 48,49 . Studies which combined long read the cell numbers for these studies are limited compared to short read RNA-Seq, an increased throughput can potentially enable the profiling of individual isoforms in thousands of cells with long read RNA-Seq.…”
Section: Discussionmentioning
confidence: 99%
“…The latter is supported by an early single cell study 2 . Recently by analyzing the splice junctions using short-read scRNA-seq data, splicing in homogeneous cell populations has been found to be largely unimodal 20 . Here we expanded the binomial model from considering single splice junctions to complete isoforms in order to estimate the isoform choice between the major isoform and other isoforms (see Methods).…”
Section: Single-cell Isoform Detection and Quantification With Flamesmentioning
confidence: 99%
“…Ever since the publication of the first scRNA-seq studies, short reads have been used to answer this question, usually via the characterization of splicing event -rather than isoform expression-modalities. Successive studies have provided non-conclusive results, with evidence of bimodal splicing patterns 22,37,38 as well as concerns regarding the relationship between bimodal isoform detection and technical noise 18,39 , a controversy that suggests that new analytical and computational approaches are needed to understand the isoform landscape of single cells.…”
Section: Introductionmentioning
confidence: 99%