Evidence map›Paper›PMID 33752595›Full record

ArticleBMC bioinformatics2021

CytoGLMM: conditional differential analysis for flow and mass cytometry experiments.

Christof Seiler, Anne-Maud Ferreira, Lisa M Kronstad, Laura J Simpson, Mathieu Le Gars, Elena Vendrame, Catherine A Blish, Susan Holmes

Abstract read
In one paragraph

Article in BMC bioinformatics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Mass cytometric analysis of circulating monocyte subsets in a murine model of diabetic gastroparesis.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. spillR: spillover compensation in mass cytometry data.Bioinformatics (Oxford, England) · 2024
    Article
  11. Article
  12. Article
  13. Computational Methods for Single-Cell Proteomics.Annual review of biomedical data science · 2023
    Review
  14. Article
  15. Advances in HIV Research Using Mass Cytometry.Current HIV/AIDS reports · 2023
    Review
  16. Article
  17. Review
  18. Article
  19. Review
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

8 authors.

Christof SeilerDepartment of Data Science and Knowledge Engineering, Maastricht University, Maastricht, The Netherlands. christof.seiler@maastrichtuniversity.nl.
Anne-Maud FerreiraDepartment of Statistics, Stanford University, Stanford, USA.
Lisa M KronstadImmunology Program, Stanford University School of Medicine, Stanford, USA.
Laura J SimpsonImmunology Program, Stanford University School of Medicine, Stanford, USA.
Mathieu Le GarsImmunology Program, Stanford University School of Medicine, Stanford, USA.
Elena VendrameImmunology Program, Stanford University School of Medicine, Stanford, USA.
Catherine A BlishImmunology Program, Stanford University School of Medicine, Stanford, USA.
Susan HolmesDepartment of Statistics, Stanford University, Stanford, USA.

Funding

Targeting natural killer cells to HIV in intravenous drug usersDP1DA046089 · NIDA · STANFORD UNIVERSITY · PI BLISH, CATHERINE A · 2018 to 2022
$3.9M
Infant immune mechanisms of HIV reservoir size and decayR01HD094718 · NICHD · UNIVERSITY OF WASHINGTON · PI JOHN-STEWART, GRACE C., LEHMAN, DARA ANN · 2017 to 2021
$3.6M
Impact of HIV exposure, feeding status, and microbiome on immune ontogeny and vaccine responses in infantsU01AI131302 · NIAID · STANFORD UNIVERSITY · PI BLISH, CATHERINE A, GRAY, CLIVE MAURICE · 2017 to 2021
$2.1M
Spectrum Stanford Center for Clinical and Translational Research and EducationTL1TR001084 · NCATS · STANFORD UNIVERSITY · PI CULLEN, MARK RICHARD, GREENBERG, HARRY BERNARD · 2013 to 2017
$1.1M
NICHD NIH HHS R01 HD094718NIDA NIH HHS DP1 DA046089NIH HHS 1F32AI126674NIH HHS TL1TR001084NIH HHS U01AI131302
6 · The paper itself

Abstract

backgroundFlow and mass cytometry are important modern immunology tools for measuring expression levels of multiple proteins on single cells. The goal is to better understand the mechanisms of responses on a single cell basis by studying differential expression of proteins. Most current data analysis tools compare expressions across many computationally discovered cell types. Our goal is to focus on just one cell type. Our narrower field of application allows us to define a more specific statistical model with easier to control statistical guarantees.

resultsDifferential analysis of marker expressions can be difficult due to marker correlations and inter-subject heterogeneity, particularly for studies of human immunology. We address these challenges with two multiple regression strategies: a bootstrapped generalized linear model and a generalized linear mixed model. On simulated datasets, we compare the robustness towards marker correlations and heterogeneity of both strategies. For paired experiments, we find that both strategies maintain the target false discovery rate under medium correlations and that mixed models are statistically more powerful under the correct model specification. For unpaired experiments, our results indicate that much larger patient sample sizes are required to detect differences. We illustrate the CytoGLMM R package and workflow for both strategies on a pregnancy dataset.

conclusionOur approach to finding differential proteins in flow and mass cytometry data reduces biases arising from marker correlations and safeguards against false discoveries induced by patient heterogeneity.

Indexed as

Flow CytometryModels, StatisticalHumansLinear ModelsSample SizeGeneralized linear mixed modelsGeneralized linear modelsHigh-dimensional cytometry

Identifiers

PMID33752595
PMCPMC7983283

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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.