Evidence map›Paper›PMID 39454576›Full record

ArticleCell2024

Method of moments framework for differential expression analysis of single-cell RNA sequencing data.

Min Cheol Kim, Rachel Gate, David S Lee, Andrew Tolopko, Andrew Lu, Erin Gordon, Eric Shifrut, Pablo E Garcia-Nieto, Alexander Marson, Vasilis Ntranos and 1 more

Abstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  20. ARTP Mutagenesis ofJournal of microbiology and biotechnology · 2025
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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.

Min Cheol KimMedical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Rachel GateInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
David S LeeInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Andrew TolopkoChan Zuckerberg Initiative, Redwood City, CA, USA.
Andrew LuInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Erin GordonDivision of Pulmonary and Critical Care, University of California, San Francisco, San Francisco, CA, USA.
Eric ShifrutDiabetes Center, University of California, San Francisco, San Francisco, CA, USA; Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Pablo E Garcia-NietoChan Zuckerberg Initiative, Redwood City, CA, USA.
Alexander MarsonDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Vasilis NtranosDiabetes Center, University of California, San Francisco, San Francisco, CA, USA; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
Chun Jimmie YeInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. Electronic address: jimmie.ye@ucsf.edu.

Funding

RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
Chemokines and Lymphoid Tissue Organization and FunctionR01AI045073 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1999 to 2023
$7.6M
Mapping gene-by-environment interactions using multiplexed single cell RNA-sequencingR01HG011239 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2020 to 2023
$4.1M
Genetic regulation and immunological function of ERAP2 haplotypesR01AI136972 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2018 to 2022
$3.5M
NHGRI NIH HHS R01 HG011239NIAID NIH HHS R01 AI045073NIAID NIH HHS R01 AI136972NIAMS NIH HHS P30 AR070155
6 · The paper itself

Abstract

Differential expression analysis of single-cell RNA sequencing (scRNA-seq) data is central for characterizing how experimental factors affect the distribution of gene expression. However, distinguishing between biological and technical sources of cell-cell variability and assessing the statistical significance of quantitative comparisons between cell groups remain challenging. We introduce Memento, a tool for robust and efficient differential analysis of mean expression, variability, and gene correlation from scRNA-seq data, scalable to millions of cells and thousands of samples. We applied Memento to 70,000 tracheal epithelial cells to identify interferon-responsive genes, 160,000 CRISPR-Cas9 perturbed T cells to reconstruct gene-regulatory networks, 1.2 million peripheral blood mononuclear cells (PBMCs) to map cell-type-specific quantitative trait loci (QTLs), and the 50-million-cell CELLxGENE Discover corpus to compare arbitrary cell groups. In all cases, Memento identified more significant and reproducible differences in mean expression compared with existing methods. It also identified differences in variability and gene correlation that suggest distinct transcriptional regulation mechanisms imparted by perturbations.

Indexed as

Quantitative Trait LociSequence Analysis, RNASingle-Cell AnalysisAnimalsCRISPR-Cas SystemsEpithelial CellsGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksHumansLeukocytes, MononuclearMiceT-LymphocytesTracheaBootstrap methodCD4 T cellsCELLxGENE DiscoverDifferential expressionGene expression varianceGene-regulatory networksMementoscRNA-seq analysisSingle-cell transcriptomicsSpatial genomics

Identifiers

PMID39454576
PMCPMC11556465

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.