Evidence map›Paper›PMID 40211002›Full record

ArticleNature methods2025

Perturb-tracing enables high-content screening of multi-scale 3D genome regulators.

Yubao Cheng, Mengwei Hu, Bing Yang, Tyler B Jensen, Yuan Zhang, Tianqi Yang, Ruihuan Yu, Zhaoxia Ma, Jonathan S D Radda, Shengyan Jin and 2 more

Abstract read
In one paragraph

Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Fast, StreamlinedChemical & biomedical imaging · 2026
    Article
  2. Article
  3. A Guide for Spatial Omics Technologies: Innovation, Evaluation, and Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Article
  5. Article
  6. Differential analysis of image-based chromatin tracing data with Dory.bioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Image-based 3D genomics through chromatin tracing.Nature reviews. Methods primers · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Yubao Cheng *Department of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-6967-1433
Mengwei Hu *Department of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0966-8720
Bing Yang *Department of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-9355-2538
Tyler B Jensen *Department of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0220-4026
Yuan ZhangDepartment of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.
Tianqi YangDepartment of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5358-9144
Ruihuan YuDepartment of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0009-0005-5101-7907
Zhaoxia MaDepartment of Genome Sciences, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-7154-2638
Jonathan S D RaddaDepartment of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-2242-9604
Shengyan JinDepartment of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8667-7586
Chongzhi ZangDepartment of Genome Sciences, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-4812-3627
Siyuan WangDepartment of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA. siyuan.wang@yale.edu.ORCID http://orcid.org/0000-0001-6550-4064

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Harriet M. Kluger · 2015 to 2026
$31.1M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007499 · NIGMS · YALE UNIVERSITY · PI CARLSON, JOHN R, REINKE, VALERIE J · 1985 to 2022
$13.9M
Integrative computational models for functional epigenomics and transcriptional regulationR35GM133712 · NIGMS · UNIVERSITY OF VIRGINIA · PI Chongzhi Zang · 2019 to 2026
$3.4M
Genome Architecture in Human Germinal Center B Cell Development, Malignancy, and Somatic HypermutationU01CA260701 · NCI · YALE UNIVERSITY · PI SCHATZ, DAVID G., WANG, SIYUAN · 2020 to 2024
$3.1M
Building the 3D genomic regulatomeDP2GM137414 · NIGMS · YALE UNIVERSITY · PI WANG, SIYUAN · 2019 to 2019
$2.5M
Spatial omics technologies to map the senescent cell microenvironmentUH3CA268202 · NCI · BROWN UNIVERSITY · PI MA, JIAN, NERETTI, NICOLA · 2023 to 2025
$2.2M
Multimodal Analysis of the Genome Architecture Using Expansion MicroscopyR01HG012969 · NHGRI · YALE UNIVERSITY · PI Joerg Bewersdorf, Antonio J Giraldez · 2024 to 2026
$2.1M
Integrative single-cell spatial genomic, transcriptomic, and epigenetic imaging in mammalian tissueR01HG011245 · NHGRI · YALE UNIVERSITY · PI WANG, SIYUAN · 2020 to 2023
$2.1M
3D genome reorganization drives cancer developmentR01CA292936 · NCI · YALE UNIVERSITY · PI Mandar Deepak Muzumdar, Siyuan Wang · 2024 to 2026
$2.1M
Developing next-generation high-content image-based genetic screens for multi-omic spatial phenotypesR01HG013503 · NHGRI · YALE UNIVERSITY · PI Siyuan Wang · 2024 to 2026
$2.0M
Multiplexed imaging of chromatin folding and RNA profiles in cancerR33CA251037 · NCI · YALE UNIVERSITY · PI MUZUMDAR, MANDAR DEEPAK, WANG, SIYUAN · 2020 to 2020
$1.2M
NCI NIH HHS P50 CA196530NCI NIH HHS R01 CA292936NCI NIH HHS R33 CA251037NCI NIH HHS U01 CA260701NCI NIH HHS UH3 CA268202NHGRI NIH HHS R01 HG011245NHGRI NIH HHS R01 HG012969NHGRI NIH HHS R01 HG013503NIGMS NIH HHS DP2 GM137414NIGMS NIH HHS R35 GM133712NIGMS NIH HHS T32 GM007205NIGMS NIH HHS T32 GM007499U.S. Department of Health & Human Services | National Institutes of Health (NIH) 2T32GM007499U.S. Department of Health & Human Services | National Institutes of Health (NIH) 5T32GM007205U.S. Department of Health & Human Services | National Institutes of Health (NIH) DP2GM137414U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35GM133712U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01HG013503
6 · The paper itself

Abstract

Three-dimensional (3D) genome organization becomes altered during development, aging and disease, but the factors regulating chromatin topology are incompletely understood and currently no technology can efficiently screen for new regulators of multi-scale chromatin organization. Here, we developed an image-based high-content screening platform (Perturb-tracing) that combines pooled CRISPR screens, a cellular barcode readout method (BARC-FISH) and chromatin tracing. We performed a loss-of-function screen in human cells, and visualized alterations to their 3D chromatin folding conformations, alongside perturbation-paired barcode readout in the same single cells. We discovered tens of new regulators of chromatin folding at different length scales, ranging from chromatin domains and compartments to chromosome territory. A subset of the regulators exhibited 3D genome effects associated with loop extrusion and A-B compartmentalization mechanisms, while others were largely unrelated to these known 3D genome mechanisms. Finally, we identified new regulators of nuclear architectures and found a functional link between chromatin compaction and nuclear shape. Altogether, our method enables scalable, high-content identification of chromatin and nuclear topology regulators that will stimulate new insights into the 3D genome.

Indexed as

ChromatinGenome, HumanCRISPR-Cas SystemsHumansIn Situ Hybridization, FluorescenceChromatin

Identifiers

PMID40211002
PMCPMC12074983

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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.