Sample, financial and labor requirements are key barriers to scaling up high-content phenotypic discovery efforts. A broadly applicable method overcomes these challenges through experimental compression (by pooling various perturbations) and computational deconvolution (of their individual effects), empowering the use of phenotypic screening to advance therapeutic discovery.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Moffat, J. G., Vincent, F., Lee, J. A., Eder, J. & Prunotto, M. Opportunities and challenges in phenotypic drug discovery: an industry perspective. Nat. Rev. Drug Discov. 16, 531–543 (2017). This review summarizes the challenges and power of cell-based phenotypic screening.
Yao, D. et al. Scalable genetic screening for regulatory circuits using compressed Perturb-seq. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01964-9 (2023). This paper reports a previous effort to compress genetic perturbations.
Cleary, B., Cong, L., Cheung, A., Lander, E. S. & Regev, A. Efficient generation of transcriptomic profiles by random composite measurements. Cell 171, 1424–1436.e18 (2017). This paper introduces a method to use composite measurements in imaging readout to increase efficiency.
Mylka, V. et al. Comparative analysis of antibody- and lipid-based multiplexing methods for single-cell RNA-seq. Genome Biol. 23, 55 (2022). This paper introduces methods for multiplexing samples to reduce costs for single-cell RNA sequencing.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Liu, N. et al. Scalable, compressed phenotypic screening using pooled perturbations. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02403-z (2024).
Rights and permissions
About this article
Cite this article
A framework for expanding discovery efforts with compressed phenotypic screens. Nat Biotechnol (2024). https://doi.org/10.1038/s41587-024-02404-y
Published:
DOI: https://doi.org/10.1038/s41587-024-02404-y
