Evidence map›Paper›PMID 32375897›Full record

ArticleGenome biology2020

Single-cell RNA-seq with spike-in cells enables accurate quantification of cell-specific drug effects in pancreatic islets.

Brenda Marquina-Sanchez, Nikolaus Fortelny, Matthias Farlik, Andhira Vieira, Patrick Collombat, Christoph Bock, Stefan Kubicek

Open access · goldAbstract readValidation Study
In one paragraph

Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
6.7field-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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

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  9. The contrasting effects of two antimalarial drugs on insulin secretion.Cellular and molecular life sciences : CMLS · 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

7 authors at 5 institutions in 2 countries.

Brenda Marquina-SanchezCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090, Vienna, Austria.
Nikolaus FortelnyCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090, Vienna, Austria.
Matthias FarlikCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090, Vienna, Austria.
Andhira VieiraUniversité Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
Patrick CollombatUniversité Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
Christoph BockCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090, Vienna, Austria. cbock@cemm.oeaw.ac.at.
Stefan KubicekCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090, Vienna, Austria. skubicek@cemm.oeaw.ac.at.
Austrian Academy of Sciences · ATCeMM Research Center for Molecular Medicine · ATInstitut de Biologie Valrose · FRMedical University of Vienna · ATUniversité Côte d'Azur · FR

Funding

The Human Islet Distribution Coordinating Center (UC4)UC4DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI EVANS-MOLINA, CARMELLA, NILAND, JOYCE CAROL · 2012 to 2017
$25.6M
Integrated Islet Distribution Program (U24) - 2021U24DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Carmella Evans-Molina, Joyce Carol Niland · 2021 to 2026
$17.8M
NIDDK NIH HHS U24 DK098085NIDDK NIH HHS UC4 DK098085
6 · The paper itself

Abstract

backgroundSingle-cell RNA-seq (scRNA-seq) is emerging as a powerful tool to dissect cell-specific effects of drug treatment in complex tissues. This application requires high levels of precision, robustness, and quantitative accuracy-beyond those achievable with existing methods for mainly qualitative single-cell analysis. Here, we establish the use of standardized reference cells as spike-in controls for accurate and robust dissection of single-cell drug responses.

resultsWe find that contamination by cell-free RNA can constitute up to 20% of reads in human primary tissue samples, and we show that the ensuing biases can be removed effectively using a novel bioinformatics algorithm. Applying our method to both human and mouse pancreatic islets treated ex vivo, we obtain an accurate and quantitative assessment of cell-specific drug effects on the transcriptome. We observe that FOXO inhibition induces dedifferentiation of both alpha and beta cells, while artemether treatment upregulates insulin and other beta cell marker genes in a subset of alpha cells. In beta cells, dedifferentiation and insulin repression upon artemether treatment occurs predominantly in mouse but not in human samples.

conclusionsThis new method for quantitative, error-correcting, scRNA-seq data normalization using spike-in reference cells helps clarify complex cell-specific effects of pharmacological perturbations with single-cell resolution and high quantitative accuracy.

Indexed as

AnimalsArtemetherCell DedifferentiationForkhead Transcription FactorsGlucagon-Secreting CellsHumansInsulin-Secreting CellsIslets of LangerhansMachine LearningMiceReference StandardsRNA-SeqSingle-Cell AnalysisSpecies SpecificityTranscriptomeArtemetherForkhead Transcription Factors

Identifiers

PMID32375897
PMCPMC7201533
OpenAlexW3022232494

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.