Evidence map›Paper›PMID 39870862›Full record

ArticleNature methods2025

A genome-wide atlas of human cell morphology.

Meraj Ramezani, Erin Weisbart, Julia Bauman, Avtar Singh, John Yong, Maria Lozada, Gregory P Way, Sanam L Kavari, Celeste Diaz, Eddy Leardini and 12 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 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing 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

42 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Meraj Ramezani *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Erin Weisbart *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6437-2458
Julia Bauman *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Avtar Singh *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
John YongCalico Life Sciences LLC, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4914-2259
Maria LozadaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Gregory P WayBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0503-9348
Sanam L KavariBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Celeste DiazBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Eddy LeardiniBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0004-8090-0355
Gunjan JetleyBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jenlu PagnottaBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5027-2256
Marzieh HaghighiBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0867-8364
Thiago M BatistaType 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Joaquín Pérez-SchindlerType 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Melina ClaussnitzerType 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2450-736X
Shantanu SinghBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3150-3025
Beth A CiminiBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9640-9318
Paul C BlaineyBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4889-8783
Anne E CarpenterBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1555-8261
Calvin H JanCalico Life Sciences LLC, South San Francisco, CA, USA.
James T NealBroad Institute of MIT and Harvard, Cambridge, MA, USA. jtneal@broadinstitute.org.ORCID http://orcid.org/0000-0002-3962-8570

Funding

Optical Functional GenomicsDP2GM146252 · NIGMS · BROAD INSTITUTE, INC. · PI NEAL, JAMES THOMAS · 2021 to 2024
$2.4M
NIGMS NIH HHS DP2 GM146252Novo Nordisk Fonden (Novo Nordisk Foundation) NNF21SA0072102U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 1DP2GM146252
6 · The paper itself

Abstract

A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries. This perturbation atlas comprises high-dimensional phenotypic profiles of individual cells with sufficient resolution to cluster thousands of human genes, reconstruct known pathways and protein-protein interaction networks, interrogate subcellular processes and identify culture media-specific responses. Using this atlas, we identify the poorly characterized disease-associated TMEM251/LYSET as a Golgi-resident transmembrane protein essential for mannose-6-phosphate-dependent trafficking of lysosomal enzymes. In sum, this perturbation atlas and screening platform represents a rich and accessible resource for connecting genes to cellular functions at scale.

Indexed as

Genome, HumanGenomicsCRISPR-Cas SystemsGenome-Wide Association StudyHumansMembrane ProteinsPhenotypeMembrane Proteins

Identifiers

PMID39870862
PMCPMC11903339

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.