Droplet scRNA-seq is not zero-inflated
Open accessAbstract
Potential users of single cell RNA-sequencing often encounter a choice between high-throughput droplet based methods and high sensitivity plate based methods. In particular there is a widespread belief that single-cell RNA-sequencing will often fail to generate measurements for particular gene, cell pairs due to molecular inefficiencies, causing data to have an overabundance of zero-values. Investigation of published data of technical controls in droplet based single cell RNA-seq experiments demonstrates the number of zeros in the data is consistent with count statistics, indicating that over-abundances of zero-values in biological data are likely due to biological variation as opposed to technical shortcomings.
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Smart-seq2 data showed zero-inflation on the single cell level, but aggregation to pseudobulk removed the excess of zero values.
“In contrast to the other technologies, the Smart-seq2 data showed zero-inflation on the single cell level (see also68,69), but aggregation to pseudobulk removed the excess of zero values.”
From scPower accelerates and optimizes the design of multi-sample single cell transcriptomic studies (2021) · cites this paper as [69]
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- Authors
- Svensson, V.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Svensson, Valentine
- ORCID
- Svensson, Valentine
- Venue
- Nature Biotechnology
- Publisher
- openRxiv
- Published
- 2019-03-19
- Volume
- 38
- Issue
- 2
- Pages
- 147-150
- ISSN
- 0733-222X (ISSN-L)
- OpenAlex
- W3000145506
- Cited by
- 356
- References
- 40
- Citations by year
- 2026: 33 · 2025: 40 · 2024: 46 · 2023: 61 · 2022: 63 · 2021: 63 · 2020: 37 · 2019: 13
- FWCI
- 18.67
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Biotechnology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- U.S. Department of Health and Human Services (U19MH114830)
- European Molecular Biology Laboratory
- National Institutes of Health
- National Institute of Mental Health (U19MH114830)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- excess zeros, single-cell transcriptomics, data quality assessment
- MeSH terms
- Animals, Cell Line, Humans, Models, Statistical, Sequence Analysis, RNA, Microfluidics, Mice, Single-Cell Analysis
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