Evidence map›Paper›PMID 33548142›Full record

ArticleEuropean journal of immunology2021

Highly multiplexed tissue imaging using repeated oligonucleotide exchange reaction.

Julia Kennedy-Darling, Salil S Bhate, John W Hickey, Sarah Black, Graham L Barlow, Gustavo Vazquez, Vishal G Venkataraaman, Nikolay Samusik, Yury Goltsev, Christian M Schürch and 1 more

Open access · hybridAbstract read
In one paragraph

Article in European journal of immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

71 citing papers in PubMed, 101 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Spatium: A Protein Language Foundation Model for Spatial Proteomics.bioRxiv : the preprint server for biology · 2026
    Article
  5. Investigating Spatial Dynamics in Spatial Omics Data with StarTrail.Journal of the American Statistical Association · 2026
    Article
  6. Subcellular localization as a driver of protein function.Nature reviews. Molecular cell biology · 2026
    Review
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  8. Article
  9. Article
  10. Article
  11. Single-Cell Protein Assays in Context: From 2D to 3D and In Situ Analysis.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026
    Review
  12. Review
  13. Article
  14. Comparative Evaluation of Antibody-Oligonucleotide Conjugation Strategies for Multiplexed Imaging Applications.Laboratory investigation; a journal of technical methods and pathology · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

11 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

11 authors at 3 institutions in 2 countries.

Julia Kennedy-DarlingDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Salil S BhateDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-2057-9182
John W HickeyDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-9961-7673
Sarah BlackDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-8098-0576
Graham L BarlowDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-9335-5414
Gustavo VazquezDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Vishal G VenkataraamanDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Nikolay SamusikDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-3559-1010
Yury GoltsevDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-4079-7969
Christian M SchürchDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-1792-1768
Garry P NolanDepartment of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-8862-9043
Stanford University · USKennedy Center · DKBecton Dickinson (United States) · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Systems Biology CoreU19AI100627 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ULEVITCH, RICHARD J · 2012 to 2021
$49.1M
The Cellular Response to Elafin in PAHP01HL108797 · NHLBI · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2011 to 2021
$19.7M
Technology CoreU19AI135976 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI ADEREM, ALAN A · 2018 to 2022
$17.0M
The Cellular Geography of Therapeutic Resistance in CancerU2CCA233195 · NCI · DANA-FARBER CANCER INST · PI JOHNSON, BRUCE E. · 2018 to 2023
$13.7M
Project 3: Identifying plasma biomarkers predicting time to HIV rebound after treatment interruptionP01AI131374 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI PILLAI, SATISH KUMAR · 2017 to 2021
$8.5M
The Lung PCA: A Multi-Dimensional Atlas of Pulmonary PremalignancyU2CCA233238 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI DUBINETT, STEVEN M., SPIRA, AVRUM E · 2018 to 2021
$7.0M
Stanford Tissue Mapping CenterU54HG010426 · NHGRI · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2018 to 2021
$5.1M
Tissue Cytokine Sequestration and Immune Regulation in AutoimmunityU01AI101984 · NIAID · STANFORD UNIVERSITY · PI BOLLYKY, PAUL L · 2012 to 2021
$5.0M
Multiscale Modeling of Myelodysplastic SyndromesR01HL128173 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI COREY, SETH JOEL, KIMMEL, MAREK · 2015 to 2019
$3.8M
Balanced signaling cues to guide cell transitions in the blood lineage continuumR01HL120724 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAKRABORTY, ARUP K., NOLAN, GARRY P · 2015 to 2019
$3.7M
T Cell Reagent Research for Monitoring T Cell in Food AllergyU01AI140498 · NIAID · STANFORD UNIVERSITY · PI NADEAU, KARI C. · 2018 to 2022
$1.8M
Cancer Research UK 27145Cancer Research UK C27165/A29073NCI NIH HHS F32 CA233203NCI NIH HHS F99 CA212231NCI NIH HHS R33 CA183692NCI NIH HHS T32 CA196585NCI NIH HHS U2C CA233195NCI NIH HHS U2C CA233238NHGRI NIH HHS U54 HG010426NHLBI NIH HHS P01 HL108797NHLBI NIH HHS R01 HL120724NHLBI NIH HHS R01 HL128173NIAID NIH HHS P01 AI131374NIAID NIH HHS U01 AI101984NIAID NIH HHS U01 AI140498NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI100627NIAID NIH HHS U19 AI135976NIDDK NIH HHS UG3 DK114937
6 · The paper itself

Abstract

Multiparameter tissue imaging enables analysis of cell-cell interactions in situ, the cellular basis for tissue structure, and novel cell types that are spatially restricted, giving clues to biological mechanisms behind tissue homeostasis and disease. Here, we streamlined and simplified the multiplexed imaging method CO-Detection by indEXing (CODEX) by validating 58 unique oligonucleotide barcodes that can be conjugated to antibodies. We showed that barcoded antibodies retained their specificity for staining cognate targets in human tissue. Antibodies were visualized one at a time by adding a fluorescently labeled oligonucleotide complementary to oligonucleotide barcode, imaging, stripping, and repeating this cycle. With this we developed a panel of 46 antibodies that was used to stain five human lymphoid tissues: three tonsils, a spleen, and a LN. To analyze the data produced, an image processing and analysis pipeline was developed that enabled single-cell analysis on the data, including unsupervised clustering, that revealed 31 cell types across all tissues. We compared cell-type compositions within and directly surrounding follicles from the different lymphoid organs and evaluated cell-cell density correlations. This sequential oligonucleotide exchange technique enables a facile imaging of tissues that leverages pre-existing imaging infrastructure to decrease the barriers to broad use of multiplexed imaging.

Indexed as

AntibodiesOligonucleotidesCell CommunicationCell CountHistocytochemistryHumansIn Situ HybridizationLymphoid TissueMolecular ImagingOrgan SpecificityReproducibility of ResultsSensitivity and SpecificitySingle-Cell AnalysisAntibodiesOligonucleotidesCODEXDNA-conjugated antibodiesMultiplexed tissue imagingSingle-cell analysisSpatial single-cell biology

Identifiers

PMID33548142
PMCPMC8251877
OpenAlexW3126476181

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.