Evidence map›Paper›PMID 37697162›Full record

ArticleNature methods2023

Recovery of missing single-cell RNA-sequencing data with optimized transcriptomic references.

Allan-Hermann Pool, Helen Poldsam, Sisi Chen, Matt Thomson, Yuki Oka

Abstract read
PubMed Publisher
In one paragraph

Article in Nature methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
7.1field-weighted citation impact, top 2% of its field
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

37 citing papers in PubMed, 46 citations in OpenAlex.

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  18. Astrocyte regional specialization is shaped by postnatal development.bioRxiv : the preprint server for biology · 2025
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  20. Mimicking opioid analgesia in cortical pain circuits.bioRxiv : the preprint server for biology · 2025
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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

5 authors at 3 institutions in 2 countries.

Allan-Hermann PoolDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA. allan-hermann.pool@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-0811-9861
Helen PoldsamDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sisi ChenDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Matt ThomsonDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Yuki OkaDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. yoka@caltech.edu.ORCID http://orcid.org/0000-0003-2686-0677
California Institute of Technology · USSouthwestern Medical Center · USTallinn University of Technology · EE

Funding

Dissecting sodium appetite circuits in the mammalian brainR01NS123918 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI OKA, YUKI · 2021 to 2025
$2.0M
Neural circuits underlying thirst and satiety regulationR01NS109997 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI OKA, YUKI · 2018 to 2022
$1.9M
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS109997U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS123918
6 · The paper itself

Abstract

Single-cell RNA-sequencing (scRNA-seq) is an indispensable tool for characterizing cellular diversity and generating hypotheses throughout biology. Droplet-based scRNA-seq datasets often lack expression data for genes that can be detected with other methods. Here we show that the observed sensitivity deficits stem from three sources: (1) poor annotation of 3' gene ends; (2) issues with intronic read incorporation; and (3) gene overlap-derived read loss. We show that missing gene expression data can be recovered by optimizing the reference transcriptome for scRNA-seq through recovering false intergenic reads, implementing a hybrid pre-mRNA mapping strategy and resolving gene overlaps. We demonstrate, with a diverse collection of mouse and human tissue data, that reference optimization can substantially improve cellular profiling resolution and reveal missing cell types and marker genes. Our findings argue that transcriptomic references need to be optimized for scRNA-seq analysis and warrant a reanalysis of previously published datasets and cell atlases.

Indexed as

Gene Expression ProfilingRNA-SeqSequence Analysis, RNASingle-Cell AnalysisTranscriptomeAnimalsHumansMice

Identifiers

PMID37697162
OpenAlexW4386609875

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.