Evidence map›Paper›PMID 39375448›Full record

ArticleNature biotechnology2025

Mapping multimodal phenotypes to perturbations in cells and tissue with CRISPRmap.

Jiacheng Gu, Abhishek Iyer, Ben Wesley, Angelo Taglialatela, Giuseppe Leuzzi, Sho Hangai, Aubrianna Decker, Ruoyu Gu, Naomi Klickstein, Yuanlong Shuai and 17 more

Erratum issuedAbstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. A pooled image-based CRISPR screen identifies EAF1 as abioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. A Guide for Spatial Omics Technologies: Innovation, Evaluation, and Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Probing neuropsychiatric disorders through in vivo CRISPR screening.Current opinion in genetics & development · 2026
    Review
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Jiacheng GuDepartment of Biological Sciences, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-1543-9684
Abhishek IyerDepartment of Biological Sciences, Columbia University, New York, NY, USA.
Ben WesleyDepartment of Biological Sciences, Columbia University, New York, NY, USA.
Angelo TaglialatelaDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Giuseppe LeuzziDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-2211-790X
Sho HangaiHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
Aubrianna DeckerDepartment of Biological Sciences, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-0646-1815
Ruoyu GuDepartment of Biological Sciences, Columbia University, New York, NY, USA.
Naomi KlicksteinDepartment of Biological Sciences, Columbia University, New York, NY, USA.
Yuanlong ShuaiDepartment of Biological Sciences, Columbia University, New York, NY, USA.
Kristina JankovicHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
Lucy Parker-BurnsHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
Yinuo JinDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-1889-8587
Jia Yi ZhangDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Justin HongDepartment of Computer Science, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-2115-9101
Xiang NiuGenentech Research and Early Development, New York, NY, USA.
Jonathon A CostaDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Mikael G PezetDepartment of Medicine, Columbia Center for Stem Cell Therapies, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Jacqueline ChouDepartment of Biological Sciences, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-4553-4914
Cao 'Claire' ChenDepartment of Biological Sciences, Columbia University, New York, NY, USA.ORCID http://orcid.org/0009-0003-2441-4662
Margaret PaivaDepartment of Biological Sciences, Columbia University, New York, NY, USA.ORCID http://orcid.org/0009-0004-9094-6090
Hans-Willem SnoeckDepartment of Medicine, Columbia Center for Stem Cell Therapies, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.ORCID http://orcid.org/0000-0001-8375-995X
Dan A LandauNew York Genome Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-2346-9541
Elham AziziDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0001-5059-6971
Edmond M ChanHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
Alberto CicciaDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-4789-6564
Jellert T GaublommeDepartment of Biological Sciences, Columbia University, New York, NY, USA. jg4106@columbia.edu.ORCID http://orcid.org/0000-0002-1266-052X

Funding

Replication fork remodeling and genomic stabilityR01CA197774 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Alberto Ciccia · 2016 to 2026
$4.2M
SPATIALLY MAPPING OF POOLED IN VIVO CRISPR SCREENS IN THE TUMOR MICROENVIRONMENTDP2CA281605 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GAUBLOMME, JELLERT · 2022 to 2025
$2.5M
Restoring genome stability and tumor suppression in BRCA1 deficient cellsR01CA227450 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BAER, RICHARD J, CICCIA, ALBERTO · 2019 to 2022
$2.1M
Machine learning methods for interpreting spatial multi-omics dataR01HG012875 · NHGRI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Elham Azizi · 2023 to 2026
$1.7M
Expanding the GoT toolkit to link single-cell clonal genotypes with protein, transcriptomic, epigenomic and spatial phenotypesR33CA267219 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LANDAU, DAN · 2022 to 2024
$1.2M
Advancing WRN as a synthetic lethal target for microsatellite unstable CancersK08CA256173 · NCI · DANA-FARBER CANCER INST · PI CHAN, EDMOND · 2021 to 2025
$1.1M
Single-Cell Multi-omics to Link Clonal Mosaicism (CM) Genotypes with Chromatin, Epigenomic, Transcriptomic and Protein PhenotypesUG3NS132139 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI LANDAU, DAN, SATIJA, RAHUL · 2023 to 2024
$834k
Computational toolbox for spatial transcriptomic analysis of complex tissuesR21HG012639 · NHGRI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI AZIZI, ELHAM · 2023 to 2023
$435k
Cancer Research Institute (CRI) Lloyd J. Old STAR awardNCI NIH HHS DP2 CA281605NCI NIH HHS K08 CA256173NCI NIH HHS R01 CA197774NCI NIH HHS R01 CA227450NCI NIH HHS R33 CA267219NHGRI NIH HHS R01 HG012875NHGRI NIH HHS R21 HG012639NINDS NIH HHS UG3 NS132139U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1DP2CA281605U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 5R01CA197774-04U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 5R01CA227450-04U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) 1R01HG012875-01U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) 1R21HG012639-01A1
6 · The paper itself

Abstract

Unlike sequencing-based methods, which require cell lysis, optical pooled genetic screens enable investigation of spatial phenotypes, including cell morphology, protein subcellular localization, cell-cell interactions and tissue organization, in response to targeted CRISPR perturbations. Here we report a multimodal optical pooled CRISPR screening method, which we call CRISPRmap. CRISPRmap combines in situ CRISPR guide-identifying barcode readout with multiplexed immunofluorescence and RNA detection. Barcodes are detected and read out through combinatorial hybridization of DNA oligos, enhancing barcode detection efficiency. CRISPRmap enables in situ barcode readout in cell types and contexts that were elusive to conventional optical pooled screening, including cultured primary cells, embryonic stem cells, induced pluripotent stem cells, derived neurons and in vivo cells in a tissue context. We conducted a screen in a breast cancer cell line of the effects of DNA damage repair gene variants on cellular responses to commonly used cancer therapies, and we show that optical phenotyping pinpoints likely pathogenic patient-derived mutations that were previously classified as variants of unknown clinical significance.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsAnimalsBreast NeoplasmsCell Line, TumorHumansInduced Pluripotent Stem CellsMicePhenotype

Identifiers

PMID39375448
PMCPMC12263428

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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.