ArticleeLife2020
Coverage-dependent bias creates the appearance of binary splicing in single cells.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 55 citations in OpenAlex.
- Review
- T Cell Heterogeneity Shaped by Alternative Splicing Predicts Prognosis in Hepatocellular Carcinoma.Cancer science · 2026Article
- Single cell analysis of developing Merkel cells reveals the emergence of non-coding RNA biotypes as a hallmark of terminal differentiation.Cell death and differentiation · 2026Article
- Comprehensive assessment of alternative splicing analysis methods for single-cell RNA-seq.iScience · 2026Article
- Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM.Nature biotechnology · 2026Article
- Single cell and spatial alternative splicing analysis with Nanopore long read sequencing.Nature communications · 2025Article
- DOLPHIN advances single-cell transcriptomics beyond gene level by leveraging exon and junction reads.Nature communications · 2025Article
- Deep transcriptomics reveals cell-specific isoforms of pan-neuronal genes.Nature communications · 2025Article
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- Characterization of alternative splicing during mammalian brain development reveals the extent of isoform diversity and potential effects on protein structural changes.Biology open · 2024Article
- Interrogations of single-cell RNA splicing landscapes with SCASL define new cell identities with physiological relevance.Nature communications · 2024Article
- The problem of selection bias in studies of pre-mRNA splicing.Nature communications · 2023Article
- MARVEL: an integrated alternative splicing analysis platform for single-cell RNA sequencing data.Nucleic acids research · 2023Article
- Article
- Alternative splicing in shaping the molecular landscape of the cochlea.Frontiers in cell and developmental biology · 2023Review
- Alternative splicing as a source of phenotypic diversity.Nature reviews. Genetics · 2022Review
- Diverse cell-specific patterns of alternative polyadenylation in Drosophila.Nature communications · 2022Article
- acorde unravels functionally interpretable networks of isoform co-usage from single cell data.Nature communications · 2022Article
- Sensory neuron transcriptomes reveal complex neuron-specific function and regulation of mec-2/Stomatin splicing.Nucleic acids research · 2022Article
- Robust and annotation-free analysis of alternative splicing across diverse cell types in mice.eLife · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Single-cell RNA sequencing provides powerful insight into the factors that determine each cell's unique identity. Previous studies led to the surprising observation that alternative splicing among single cells is highly variable and follows 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 pattern arises almost entirely from technical limitations. We analyze alternative splicing in human and mouse single-cell RNA-seq datasets, and model them with a probabilistic simulator. Our simulations show that low gene expression and low capture efficiency distort the observed distribution of isoforms. This gives the appearance of binary splicing outcomes, even when the underlying reality is consistent with more than one isoform per cell. We show that accounting for the true amount of information recovered can produce biologically meaningful measurements of splicing in single cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.