Evidence map›Paper›PMID 41402283›Full record

ArticleNature communications2025

A pooled Cell Painting CRISPR screening platform enables de novo inference of gene function by self-supervised deep learning.

Srinivasan Sivanandan, Bobby Leitmann, Eric Lubeck, Mohammad Muneeb Sultan, Panagiotis Stanitsas, Navpreet Ranu, Alexis Ewer, Jordan E Mancuso, Zachary F Phillips, Albert Kim and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

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  15. Integrating Biological Knowledge for Robust Microscopy Image Profiling onProceedings. IEEE International Conference on Computer Vision · 2025
    Article
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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

19 authors.

Srinivasan Sivanandan *Insitro Inc, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1500-4082
Bobby Leitmann *Insitro Inc, South San Francisco, CA, USA.
Eric LubeckInsitro Inc, South San Francisco, CA, USA.
Mohammad Muneeb SultanInsitro Inc, South San Francisco, CA, USA.
Panagiotis StanitsasInsitro Inc, South San Francisco, CA, USA.
Navpreet RanuInsitro Inc, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5412-8200
Alexis EwerInsitro Inc, South San Francisco, CA, USA.
Jordan E MancusoInsitro Inc, South San Francisco, CA, USA.ORCID http://orcid.org/0009-0004-1681-9405
Zachary F PhillipsInsitro Inc, South San Francisco, CA, USA.
Albert KimInsitro Inc, South San Francisco, CA, USA.
John W BisognanoInsitro Inc, South San Francisco, CA, USA.
John CesarekInsitro Inc, South San Francisco, CA, USA.
Fiorella RuggiuInsitro Inc, South San Francisco, CA, USA.
David FeldmanInsitro Inc, South San Francisco, CA, USA.
Daphne KollerInsitro Inc, South San Francisco, CA, USA. daphne@insitro.com.ORCID http://orcid.org/0009-0007-1645-951X
Eilon SharonInsitro Inc, South San Francisco, CA, USA. eilon@insitro.com.
Ajamete KaykasInsitro Inc, South San Francisco, CA, USA. akaykas@insitro.com.
Max R SalickInsitro Inc, South San Francisco, CA, USA. max@insitro.com.ORCID http://orcid.org/0000-0002-0631-1083
Ci ChuInsitro Inc, South San Francisco, CA, USA. chuci393@gmail.com.ORCID http://orcid.org/0009-0000-9488-0034

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pooled CRISPR screening enables large-scale interrogation of gene functions but typically measures simple phenotypes such as fitness. High-content methods like Perturb-seq extend dimensionality to transcriptomics but are costly and limited in scope. Optical pooled screening (OPS) combines pooled CRISPR screening with imaging to yield scalable, information-rich readouts, yet existing implementations remain pathway-specific. Here we describe an OPS-compatible Cell Painting platform that enables hypothesis-free reverse genetic screening through multiplexed morphological profiling. We validate this technique using a well-defined morphological gene set, compare classical image analysis to self-supervised learning methods using a mechanism-of-action library, and perform discovery screening with a druggable genome library. By combining rich morphological data with deep learning, gene networks emerge without the need for target-specific biomarkers, leading to unbiased discovery of gene functions.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDeep LearningGene Regulatory NetworksHumans

Identifiers

PMID41402283
PMCPMC12770385

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.