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Statistics or biology: the zero-inflation controversy about scRNA-seq data

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Jiang, Ruochen, Sun, Tianyi, Song, Dongyuan, Li, Jingyi Jessica·2022·Genome Biology
DOI 10.1186/s13059-022-02601-5PMC PMC8783472

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Abstract

Researchers view vast zeros in single-cell RNA-seq data differently: some regard zeros as biological signals representing no or low gene expression, while others regard zeros as missing data to be corrected. To help address the controversy, here we discuss the sources of biological and non-biological zeros; introduce five mechanisms of adding non-biological zeros in computational benchmarking; evaluate the impacts of non-biological zeros on data analysis; benchmark three input data types: observed counts, imputed counts, and binarized counts; discuss the open questions regarding non-biological zeros; and advocate the importance of transparent analysis.

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  • Zero-valued entries in a gene expression matrix have both biological and technical origins.

    “Zero valued entries in a gene expression matrix have both biological and technical origins,75 and it is important to prioritize preserving relevant biological signals while reducing technical noise.”

    From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [75]

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Cited by

Sorted by citations

Authors
Jiang, R., Sun, T., Song, D., & Li, J. J.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Li, Jingyi Jessica
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2022-01-21
Volume
23
Issue
1
Pages
31-31
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/s13059-022-02601-5
PMC
PMC8783472
OpenAlex
W4225981439
Cited by
614
References
23
Citations by year
2026: 92 · 2025: 143 · 2024: 158 · 2023: 150 · 2022: 66 · 2021: 3 · 2020: 1 · 2019: 1
FWCI
13.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Institute of General Medical Sciences (R01GM120507, R35GM140888)
  • Directorate for Biological Sciences (1846216)
  • Directorate for Mathematical and Physical Sciences (2113754)
  • Johnson and Johnson (WiSTEM2D Award)
  • Alfred P. Sloan Foundation (Sloan Research Fellowship)
  • W. M. Keck Foundation (UCLA David Geffen School of Medicine W.M. Keck Foundation Junior Faculty Award)
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 RNA sequencing, benchmarking
MeSH terms
Exome Sequencing, Biology, Sequence Analysis, RNA, Benchmarking, Single-Cell Analysis

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