Evidence map›Paper›PMID 37528072›Full record

ArticleNature communications2023

Robust phenotyping of highly multiplexed tissue imaging data using pixel-level clustering.

Candace C Liu, Noah F Greenwald, Alex Kong, Erin F McCaffrey, Ke Xuan Leow, Dunja Mrdjen, Bryan J Cannon, Josef Lorenz Rumberger, Sricharan Reddy Varra, Michael Angelo

Abstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing 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

66 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Integrating Spatial Proteogenomics in Cancer Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

6 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.

Candace C LiuDepartment of Pathology, Stanford University, Stanford, CA, USA.
Noah F GreenwaldDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-7836-4379
Alex KongDepartment of Pathology, Stanford University, Stanford, CA, USA.
Erin F McCaffreyDepartment of Pathology, Stanford University, Stanford, CA, USA.
Ke Xuan LeowDepartment of Pathology, Stanford University, Stanford, CA, USA.
Dunja MrdjenDepartment of Pathology, Stanford University, Stanford, CA, USA.
Bryan J CannonDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-4418-1803
Josef Lorenz RumbergerMax-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
Sricharan Reddy VarraDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0009-0000-5757-6818
Michael AngeloDepartment of Pathology, Stanford University, Stanford, CA, USA. mangelo0@stanford.edu.ORCID 0000-0003-1531-5067

Funding

MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0M
Stanford Cancer Immune Monitoring and Analysis Center (CIMAC)U24CA224309 · NCI · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Holden T. Maecker · 2017 to 2026
$19.9M
Investigating the latent HIV-1 reservoir in lymphoid tissue using multiplexed imaging and spatial transcriptomicsF31AI165180 · NIAID · STANFORD UNIVERSITY · PI LIU, CANDACE · 2022 to 2023
$80k
Comprehensive profiling of the tumor microenvironment to predict patient response to immunotherapyF99CA264307 · NCI · STANFORD UNIVERSITY · PI GREENWALD, NOAH · 2021 to 2022
$79k
Predicting response to anti-PD-1 therapy in triple negative breast cancer by comprehensive profiling of the tumor microenvironmentF31CA246880 · NCI · STANFORD UNIVERSITY · PI GREENWALD, NOAH · 2020 to 2021
$53k
NCI NIH HHS F31 CA246880NCI NIH HHS F99 CA264307NCI NIH HHS U24 CA224309NIAID NIH HHS F31 AI165180NIAID NIH HHS T32 AI007290Wellcome Trust
6 · The paper itself

Abstract

While technologies for multiplexed imaging have provided an unprecedented understanding of tissue composition in health and disease, interpreting this data remains a significant computational challenge. To understand the spatial organization of tissue and how it relates to disease processes, imaging studies typically focus on cell-level phenotypes. However, images can capture biologically important objects that are outside of cells, such as the extracellular matrix. Here, we describe a pipeline, Pixie, that achieves robust and quantitative annotation of pixel-level features using unsupervised clustering and show its application across a variety of biological contexts and multiplexed imaging platforms. Furthermore, current cell phenotyping strategies that rely on unsupervised clustering can be labor intensive and require large amounts of manual cluster adjustments. We demonstrate how pixel clusters that lie within cells can be used to improve cell annotations. We comprehensively evaluate pre-processing steps and parameter choices to optimize clustering performance and quantify the reproducibility of our method. Importantly, Pixie is open source and easily customizable through a user-friendly interface.

Indexed as

Diagnostic ImagingCluster AnalysisReproducibility of Results

Identifiers

PMID37528072
PMCPMC10393943

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.