Evidence map›Paper›PMID 34031584›Full record

ReviewNature genetics2021

Separating measurement and expression models clarifies confusion in single-cell RNA sequencing analysis.

Abhishek Sarkar, Matthew Stephens

Abstract readReview
In one paragraph

Review in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

138 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  17. Distinguishing causal from tagging enhancers using single-cell multiome data.medRxiv : the preprint server for health sciences · 2026
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78 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Abhishek SarkarDepartment of Human Genetics, University of Chicago, Chicago, IL, USA. aksarkar@uchicago.edu.ORCID http://orcid.org/0000-0002-4636-9255
Matthew StephensDepartment of Human Genetics, University of Chicago, Chicago, IL, USA. mstephens@uchicago.edu.ORCID http://orcid.org/0000-0001-5397-9257

Funding

Genome analysis: statistical methods and applicationsR01HG002585 · NHGRI · UNIVERSITY OF WASHINGTON · PI MATTHEW STEPHENS · 2002 to 2026
$8.4M
Genome analysis: statistical methods and applicationsR56HG002585 · NHGRI · UNIVERSITY OF CHICAGO · PI STEPHENS, MATTHEW · 2023 to 2023
$292k
NHGRI NIH HHS R01 HG002585NHGRI NIH HHS R56 HG002585
6 · The paper itself

Abstract

The high proportion of zeros in typical single-cell RNA sequencing datasets has led to widespread but inconsistent use of terminology such as dropout and missing data. Here, we argue that much of this terminology is unhelpful and confusing, and outline simple ideas to help to reduce confusion. These include: (1) observed single-cell RNA sequencing counts reflect both true gene expression levels and measurement error, and carefully distinguishing between these contributions helps to clarify thinking; and (2) method development should start with a Poisson measurement model, rather than more complex models, because it is simple and generally consistent with existing data. We outline how several existing methods can be viewed within this framework and highlight how these methods differ in their assumptions about expression variation. We also illustrate how our perspective helps to address questions of biological interest, such as whether messenger RNA expression levels are multimodal among cells.

Indexed as

Gene Expression RegulationSequence Analysis, RNASingle-Cell AnalysisHumansModels, GeneticPoisson DistributionTerminology as Topic

Identifiers

PMID34031584
PMCPMC8370014

What OpenQuestion holds

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Registered trials

None linked

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.