Evidence map›Paper›PMID 33558698›Full record

ArticleNature biotechnology2021

Quantifying the effect of experimental perturbations at single-cell resolution.

Daniel B Burkhardt, Jay S Stanley, Alexander Tong, Ana Luisa Perdigoto, Scott A Gigante, Kevan C Herold, Guy Wolf, Antonio J Giraldez, David van Dijk, Smita Krishnaswamy

Abstract read
In one paragraph

Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed
–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

125 citing papers in PubMed.

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  10. Review
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  14. Review
  15. Single-cell transcriptional changes of artemisinin-sensitive K13Frontiers in cellular and infection microbiology · 2026
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

65 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

10 authors.

Daniel B Burkhardt *Department of Genetics, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-7744-1363
Jay S Stanley *Computational Biology & Bioinformatics Program, Yale University, New Haven, CT, USA.
Alexander TongDepartment of Computer Science, Yale University, New Haven, CT, USA.
Ana Luisa PerdigotoDepartment of Immunobiology, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-0348-9329
Scott A GiganteComputational Biology & Bioinformatics Program, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-4544-2764
Kevan C HeroldDepartment of Immunobiology, Yale University, New Haven, CT, USA.
Guy WolfDepartment of Mathematics and Statistics, Université de Montréal, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-6740-059X
Antonio J GiraldezDepartment of Genetics, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-6823-137X
David van DijkDepartment of Internal Medicine (Cardiology), Yale University, New Haven, CT, USA. david.vandijk@yale.edu.ORCID http://orcid.org/0000-0003-3911-9925
Smita KrishnaswamyDepartment of Genetics, Yale University, New Haven, CT, USA. smita.krishnaswamy@yale.edu.ORCID http://orcid.org/0000-0001-5823-1985

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
MEDICAL INFORMATICS RESEARCH TRAINING AT YALET15LM007056 · NLM · YALE UNIVERSITY · PI Mark Bender Gerstein, LUCILA OHNO-MACHADO · 1987 to 2026
$22.2M
Deciphering the regulatory code that specifies different cell fates in development using single cell genomicsR01HD100035 · NICHD · YALE UNIVERSITY · PI GIRALDEZ, ANTONIO J, KRISHNASWAMY, SMITA · 2020 to 2024
$2.8M
Deciphering Genetic and Epigenetic Regulatory Logic of Germ Layer Differentiation with Manifold LearningR01GM130847 · NIGMS · YALE UNIVERSITY · PI KRISHNASWAMY, SMITA · 2019 to 2023
$2.0M
Finding emergent structure in multi-sample biological data with the dual geometry of cells and features R01GM135929 · NIGMS · MICHIGAN STATE UNIVERSITY · PI BROWN, EDWARD · 2019 to 2022
$1.4M
Single-cell gene expression dynamics during neurogenesisF31HD097958 · NICHD · YALE UNIVERSITY · PI BURKHARDT, DANIEL · 2019 to 2021
$83k
NCATS NIH HHS UL1 TR001863NICHD NIH HHS F31 HD097958NICHD NIH HHS R01 HD100035NIGMS NIH HHS R01 GM130847NIGMS NIH HHS R01 GM135929NLM NIH HHS T15 LM007056
6 · The paper itself

Abstract

Current methods for comparing single-cell RNA sequencing datasets collected in multiple conditions focus on discrete regions of the transcriptional state space, such as clusters of cells. Here we quantify the effects of perturbations at the single-cell level using a continuous measure of the effect of a perturbation across the transcriptomic space. We describe this space as a manifold and develop a relative likelihood estimate of observing each cell in each of the experimental conditions using graph signal processing. This likelihood estimate can be used to identify cell populations specifically affected by a perturbation. We also develop vertex frequency clustering to extract populations of affected cells at the level of granularity that matches the perturbation response. The accuracy of our algorithm at identifying clusters of cells that are enriched or depleted in each condition is, on average, 57% higher than the next-best-performing algorithm tested. Gene signatures derived from these clusters are more accurate than those of six alternative algorithms in ground truth comparisons.

Indexed as

Computational BiologyAlgorithmsCluster AnalysisComputer SimulationHumansLikelihood FunctionsSequence Analysis, RNASingle-Cell AnalysisTranscriptome

Identifiers

PMID33558698
PMCPMC8122059

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.