Evidence map›Paper›PMID 40513557›Full record

ArticleCell2025

Perturb-Multimodal: A platform for pooled genetic screens with imaging and sequencing in intact mammalian tissue.

Reuben A Saunders, William E Allen, Xingjie Pan, Jaspreet Sandhu, Jiaqi Lu, Thomas K Lau, Karina Smolyar, Zuri A Sullivan, Catherine Dulac, Jonathan S Weissman and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing 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

33 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. The diverse functions of viral microproteins.bioRxiv : the preprint server for biology · 2026
    Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. A Guide for Spatial Omics Technologies: Innovation, Evaluation, and Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  15. Review
  16. Review
  17. bioRxiv : the preprint server for biology · 2026
    Article
  18. bioRxiv : the preprint server for biology · 2026
    Article
  19. Article
  20. Decoding neurodegeneration one cell at a time.The Journal of clinical investigation · 2026
    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

11 authors.

Reuben A SaundersHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Whitehead Institute, Cambridge, MA 02139, USA; University of California, San Francisco, San Francisco, CA 94158, USA.
William E AllenHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Society of Fellows, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology and Department of Physics, Harvard University, Cambridge, MA 02138, USA. Electronic address: wallen@stanford.edu.
Xingjie PanHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Chemistry and Chemical Biology and Department of Physics, Harvard University, Cambridge, MA 02138, USA.
Jaspreet SandhuHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Whitehead Institute, Cambridge, MA 02139, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.
Jiaqi LuHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Chemistry and Chemical Biology and Department of Physics, Harvard University, Cambridge, MA 02138, USA.
Thomas K LauDepartment of Statistics, Stanford University, Stanford, CA 94305, USA.
Karina SmolyarHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Whitehead Institute, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Zuri A SullivanHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Catherine DulacHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Jonathan S WeissmanHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Whitehead Institute, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: weissman@wi.mit.edu.
Xiaowei ZhuangHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Chemistry and Chemical Biology and Department of Physics, Harvard University, Cambridge, MA 02138, USA. Electronic address: zhuang@chemistry.harvard.edu.

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
RESEARCH TRAINING IN DIGESTIVE DISEASES AND NUTRITIONT32DK007191 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1986 to 2026
$14.6M
Howard Hughes Medical InstituteNHGRI NIH HHS RM1 HG009490NIDDK NIH HHS T32 DK007191
6 · The paper itself

Abstract

Metazoan life requires the coordinated activities of thousands of genes in spatially organized cell types. Understanding the basis of tissue function requires approaches to dissect the genetic control of diverse cellular and tissue phenotypes in vivo. Here, we present Perturb-Multimodal (Perturb-Multi), a paired imaging and sequencing method to construct large-scale, multimodal genotype-phenotype maps in tissues with pooled genetic perturbations. Using imaging, we identify perturbations in individual cells while simultaneously measuring their gene expression profiles and subcellular morphology. Using single-cell sequencing, we measure full transcriptomic responses to the same perturbations. We apply Perturb-Multi to study hundreds of genetic perturbations in the mouse liver. Our data suggest the genetic regulators and mechanisms underlying the dynamic control of hepatocyte zonation, the unfolded protein response, and steatosis. Perturb-Multi accelerates discoveries of the genetic basis of complex cell and tissue physiology and provides critical training data for emerging machine learning models of cellular function.

Indexed as

Genetic TestingAnimalsGene Expression ProfilingHepatocytesLiverMiceMice, Inbred C57BLPhenotypeSingle-Cell AnalysisTranscriptomeUnfolded Protein Responsehepatocyte stress responsein vivo pooled screeninglipid droplet accumulationliver zonationmachine learning morphologymultimodal phenotypingmultiplexed protein imagingmultiplexed RNA imagingRCA-MERFISHscRNA-seq

Identifiers

PMID40513557
PMCPMC12324982

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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.