Evidence map›Paper›PMID 38902848›Full record

ArticleGenomics, proteomics & bioinformatics2024

Integrated Single-cell Multiomic Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation.

Manickam Ashokkumar, Wenwen Mei, Jackson J Peterson, Yuriko Harigaya, David M Murdoch, David M Margolis, Caleb Kornfein, Alex Oesterling, Zhicheng Guo, Cynthia D Rudin and 2 more

Abstract read
In one paragraph

Article in Genomics, proteomics & bioinformatics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. 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

12 authors.

Manickam AshokkumarDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0000-0002-7880-9497
Wenwen MeiDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0009-0004-3671-8417
Jackson J PetersonHIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0000-0001-9562-2109
Yuriko HarigayaDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0000-0002-1879-5214
David M MurdochDepartment of Medicine, Duke University, Durham, NC 27708, USA.ORCID 0000-0001-7201-7950
David M MargolisDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0000-0001-5714-0002
Caleb KornfeinDepartment of Computer Science, Duke University, Durham, NC 27708, USA.ORCID 0000-0001-6796-331X
Alex OesterlingDepartment of Computer Science, Duke University, Durham, NC 27708, USA.ORCID 0000-0001-8546-0089
Zhicheng GuoDepartment of Computer Science, Duke University, Durham, NC 27708, USA.ORCID 0000-0003-3510-5358
Cynthia D RudinDepartment of Computer Science, Duke University, Durham, NC 27708, USA.ORCID 0000-0003-4283-2780
Yuchao JiangDepartment of Statistics, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0001-6905-6377
Edward P BrowneDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0000-0001-9070-7015

Funding

Collaboratory of AIDS Researchers for Eradication (CARE)UM1AI164567 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2021 to 2026
$31.6M
Collaboratory of AIDS Researchers for Eradication (CARE)UM1AI126619 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARGOLIS, DAVID M. · 2016 to 2020
$23.2M
Molecular Biology of Viral Diseases Predoctoral Training GrantT32AI007419 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Mark T Heise, CARY A MOODY · 1993 to 2026
$4.7M
POLYCOMB REPRESSIVE COMLEXE AS KEY REGULATORS OF HIV LATENCY AND TARGETS FOR LATENCY REVERSALR61DA047023 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JAMES, LINDSEY INGERMAN · 2018 to 2020
$2.7M
A machine learning framework for understanding impacts on the HIV latent reservoir size, including drugs of abuseR01DA054994 · NIDA · DUKE UNIVERSITY · PI RUDIN, CYNTHIA · 2021 to 2025
$2.3M
Statistical Methods for Bulk-Tissue and Single-Cell Multi-Omics IntegrationR35GM138342 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Yuchao Jiang · 2020 to 2026
$2.3M
Regulation of HIV Latency by Host Cell Transcriptional and Epigenetic NetworksR01AI143381 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BROWNE, EDWARD P · 2019 to 2022
$1.6M
Defining the impact of cannabinoids on the latent HIV reservoir through multi-omic analysisR33DA053599 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BROWNE, EDWARD P · 2024 to 2025
$1.5M
NIAID NIH HHS R01 AI143381NIAID NIH HHS T32 AI007419NIAID NIH HHS UM1 AI164567NIDA NIH HHS R01 DA054994NIDA NIH HHS R33 DA053599NIDA NIH HHS R61 DA047023NIGMS NIH HHS R35 GM138342
6 · The paper itself

Abstract

Despite the success of antiretroviral therapy, human immunodeficiency virus (HIV) cannot be cured because of a reservoir of latently infected cells that evades therapy. To understand the mechanisms of HIV latency, we employed an integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq) approach to simultaneously profile the transcriptomic and epigenomic characteristics of ∼ 125,000 latently infected primary CD4+ T cells after reactivation using three different latency reversing agents. Differentially expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor (TF) activities across the cell population. We identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%-79% accurate at predicting viral reactivation. Finally, we validated the role of two candidate HIV-regulating factors, FOXP1 and GATA3, in viral transcription. These data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

Indexed as

CD4-Positive T-LymphocytesGATA3 Transcription FactorHIV-1Single-Cell AnalysisVirus ActivationVirus LatencyForkhead Transcription FactorsGene Expression Regulation, ViralHIV InfectionsHumansRepressor ProteinsTranscriptomeForkhead Transcription FactorsGATA3 protein, humanGATA3 Transcription FactorRepressor ProteinsHIV latency reversalHIV-regulating factorMachine learningPrimary CD4+ T cellSingle-cell multiomics

Identifiers

PMID38902848
PMCPMC11189801

What OpenQuestion holds

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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.