Peer-Reviewed Publication
Nat Commun2025;17(1):77.December 16, 2025Journal Article

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

Srinivasan Sivanandan1, Bobby Leitmann1, Eric Lubeck1, Mohammad Muneeb Sultan1, Panagiotis Stanitsas1, Navpreet Ranu1, Alexis Ewer1, Jordan E Mancuso1, Zachary F Phillips1, Albert Kim1, John W Bisognano1, John Cesarek1, Fiorella Ruggiu1, David Feldman1, Daphne Koller2, Eilon Sharon3, Ajamete Kaykas4, Max R Salick5, Ci Chu6,7
1Insitro Inc, South San Francisco, CA, USA.
2Insitro Inc, South San Francisco, CA, USA. daphne@insitro.com.
3Insitro Inc, South San Francisco, CA, USA. eilon@insitro.com.
4Insitro Inc, South San Francisco, CA, USA. akaykas@insitro.com.
5Insitro Inc, South San Francisco, CA, USA. max@insitro.com.
6Insitro Inc, South San Francisco, CA, USA. chuci393@gmail.com.
7Xaira Therapeutics, South San Francisco, CA, USA. chuci393@gmail.com.

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 implementation…

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