Evidence map›Paper›PMID 34871816›Full record

ArticleAtherosclerosis2022

Enhanced single-cell RNA-seq workflow reveals coronary artery disease cellular cross-talk and candidate drug targets.

Wei Feng Ma, Chani J Hodonsky, Adam W Turner, Doris Wong, Yipei Song, Jose Verdezoto Mosquera, Alexandra V Ligay, Lotte Slenders, Christina Gancayco, Huize Pan and 12 more

Abstract read
In one paragraph

Article in Atherosclerosis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 2 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

37 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. NAD Metabolism Regulates Proliferation of Macrophages in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2024
    Article
  14. Conditional deletion ofAtherosclerosis plus · 2024
    Article
  15. Article
  16. Gene Regulatory Networks in Coronary Artery Disease.Current atherosclerosis reports · 2023
    Review
  17. Article
  18. Review
  19. Article
  20. High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis.medRxiv : the preprint server for health sciences · 2023
    Article
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

22 authors.

Wei Feng MaMedical Scientist Training Program, University of Virginia, Charlottesville, VA, 22908, USA; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
Chani J HodonskyCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
Adam W TurnerCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
Doris WongCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA , 22908, USA.
Yipei SongCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA; Department of Computer Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
Jose Verdezoto MosqueraCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA , 22908, USA.
Alexandra V LigayMaster of Science in Biomedical Informatics (MScBMI) Program, University of Chicago, Chicago, IL, 60637, USA.
Lotte SlendersCentral Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, 3584, CX, Utrecht, the Netherlands.
Christina GancaycoResearch Computing, University of Virginia, Charlottesville, VA, 22908, USA.
Huize PanDivision of Cardiology, Department of Medicine, Columbia University Irving Medical Center, Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, 10032, USA.
Nelson B BarrientosCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
David MaiCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
Gabriel F AlencarRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA.
Katherine OwsianyMedical Scientist Training Program, University of Virginia, Charlottesville, VA, 22908, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA.
Gary K OwensRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, 22908, USA.
Muredach P ReillyDivision of Cardiology, Department of Medicine, Columbia University Irving Medical Center, Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, 10032, USA.
Mingyao LiDepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Gerard PasterkampCentral Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, 3584, CX, Utrecht, the Netherlands.
Michal MokryCentral Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, 3584, CX, Utrecht, the Netherlands; Department of Experimental Cardiology, University Medical Center Utrecht, 3584, CX, Utrecht, the Netherlands.
Sander W van der LaanCentral Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, 3584, CX, Utrecht, the Netherlands.
Bohdan B KhomtchoukDepartment of Medicine, Section of Computational Biomedicine and Biomedical Data Science, Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL , 60637, USA. Electronic address: bohdan@uchicago.edu.
Clint L MillerCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA , 22908, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, 22908, USA. Electronic address: clintm@virginia.edu.

Funding

Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
Multimodal genetic regulatory architecture of coronary artery diseaseR01HL148239 · NHLBI · UNIVERSITY OF VIRGINIA · PI Clint L Miller · 2019 to 2026
$4.2M
Endothelial Cell to Mesenchymal Cell Transitions Play a Critical Biological Sex- and Aging-Dependent Role in Formation and Maintenance of the Acta2+ Atherosclerotic Lesion Protective Fibrous CapR01HL156849 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2022 to 2025
$3.2M
Defining SMC phenotypes critical in late stage atherosclerosis pathogenesisR01HL136314 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2018 to 2021
$3.0M
Role of Metabolic Reprogramming in Formation and Maintenance of the Acta2+ Atherosclerotic Lesion Protective Fibrous CapR01HL155165 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2021 to 2024
$2.9M
Computational and functional strategies to decipher lncRNAs in human atherosclerosisR01HL150359 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LI, MINGYAO, REILLY, MUREDACH P · 2020 to 2023
$2.7M
PDGFbeta Receptor Activation Promotes Atheroprotective Changes in SMC PhenotypeR01HL132904 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2017 to 2020
$2.6M
Third Coast HIV-Related Cardiovascular and Sleep Disorders K12 Career Development ProgramK12HL143959 · NHLBI · UNIVERSITY OF CHICAGO · PI ARDEHALI, HOSSEIN, SCHNEIDER, JOHN · 2018 to 2022
$1.5M
EPISTATIC REGULATORY MECHANISMS OF CORONARY HEART DISEASE RISKR00HL125912 · NHLBI · UNIVERSITY OF VIRGINIA · PI MILLER, CLINT L · 2017 to 2019
$747k
NCATS NIH HHS UL1 TR001873NHLBI NIH HHS K12 HL143959NHLBI NIH HHS R00 HL125912NHLBI NIH HHS R01 HL132904NHLBI NIH HHS R01 HL136314NHLBI NIH HHS R01 HL148239NHLBI NIH HHS R01 HL150359NHLBI NIH HHS R01 HL155165NHLBI NIH HHS R01 HL156849NHLBI NIH HHS T32 HL007284
6 · The paper itself

Abstract

BACKGROUND AND

aimsThe atherosclerotic plaque microenvironment is highly complex, and selective agents that modulate plaque stability are not yet available. We sought to develop a scRNA-seq analysis workflow to investigate this environment and uncover potential therapeutic approaches. We designed a user-friendly, reproducible workflow that will be applicable to other disease-specific scRNA-seq datasets.

methodsHere we incorporated automated cell labeling, pseudotemporal ordering, ligand-receptor evaluation, and drug-gene interaction analysis into a ready-to-deploy workflow. We applied this pipeline to further investigate a previously published human coronary single-cell dataset by Wirka et al. Notably, we developed an interactive web application to enable further exploration and analysis of this and other cardiovascular single-cell datasets.

resultsWe revealed distinct derivations of fibroblast-like cells from smooth muscle cells (SMCs), and showed the key changes in gene expression along their de-differentiation path. We highlighted several key ligand-receptor interactions within the atherosclerotic environment through functional expression profiling and revealed several avenues for future pharmacological development for precision medicine. Further, our interactive web application, PlaqView (www.plaqview.com), allows lay scientists to explore this and other datasets and compare scRNA-seq tools without prior coding knowledge.

conclusionsThis publicly available workflow and application will allow for more systematic and user-friendly analysis of scRNA datasets in other disease and developmental systems. Our analysis pipeline provides many hypothesis-generating tools to unravel the etiology of coronary artery disease. We also highlight potential mechanisms for several drugs in the atherosclerotic cellular environment. Future releases of PlaqView will feature more scRNA-seq and scATAC-seq atherosclerosis-related datasets to provide a critical resource for the field, and to promote data harmonization and biological interpretation.

Indexed as

Coronary Artery DiseasePharmaceutical PreparationsGene Expression ProfilingHumansRNA-SeqSequence Analysis, RNASingle-Cell AnalysisSoftwareWorkflowPharmaceutical PreparationsAtherosclerosisCardioinformaticsDrug DiscoveryPipelinePlaqViewPrecision MedicinescRNAWeb Application

Identifiers

PMID34871816
PMCPMC8919504

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.