Evidence map›Paper›PMID 39689711›Full record

ArticleCell systems2025

Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome.

Eli Metzner, Kaden M Southard, Thomas M Norman

Abstract read
In one paragraph

Article in Cell systems, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

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  12. bioRxiv : the preprint server for biology · 2026
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  19. Functional Neurogenomics to Dissect Disease Mechanisms Across Models.Annual review of genomics and human genetics · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Eli MetznerComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Tri-Institutional Training Program in Computational Biology and Medicine, New York, NY 10065, USA.
Kaden M SouthardComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Thomas M NormanComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: normantm@mskcc.org.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Deciphering the Genomics of Gene Network Regulation of T Cell and Fibroblast States in Autoimmune InflammationU01HG012103 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI Christina S Leslie, Alexander Y Rudensky · 2021 to 2026
$7.5M
Predictive engineering of cellular transcriptional stateDP2GM140925 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI NORMAN, THOMAS MAXWELL · 2020 to 2020
$2.7M
NCI NIH HHS P30 CA008748NHGRI NIH HHS U01 HG012103NIGMS NIH HHS DP2 GM140925
6 · The paper itself

Abstract

Single-cell CRISPR screens link genetic perturbations to transcriptional states, but high-throughput methods connecting these induced changes to their regulatory foundations are limited. Here, we introduce Multiome Perturb-seq, extending single-cell CRISPR screens to simultaneously measure perturbation-induced changes in gene expression and chromatin accessibility. We apply Multiome Perturb-seq in a CRISPRi screen of 13 chromatin remodelers in human RPE-1 cells, achieving efficient assignment of sgRNA identities to single nuclei via an improved method for capturing barcode transcripts from nuclear RNA. We organize expression and accessibility measurements into coherent programs describing the integrated effects of perturbations on cell state, finding that ARID1A and SUZ12 knockdowns induce programs enriched for developmental features. Modeling of perturbation-induced heterogeneity connects accessibility changes to changes in gene expression, highlighting the value of multimodal profiling. Overall, our method provides a scalable and simply implemented system to dissect the regulatory logic underpinning cell state. A record of this paper's transparent peer review process is included in the supplemental information.

Indexed as

EpigenomeTranscriptomeCell LineChromatinChromatin Assembly and DisassemblyCRISPR-Cas SystemsGene Expression ProfilingHumansSingle-Cell AnalysisChromatinchromatin accessibilityCRISPRifunctional genomicsgene regulatory networksmultiomePerturb-seqsingle-cell genomics

Identifiers

PMID39689711
PMCPMC11738662

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.