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Updated: Feb 7, 2026
08:49
Cell Surface Receptor Identification Using Genome-Scale CRISPR/Cas9 Genetic Screens
Published on: June 6, 2020
15.4K
Scaling perturbations: beyond genome-scale CRISPR screens.
Anran Tang1,2, Rico C Ardy1, Rafaela E Mendes1,3
1Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Biorxiv : the Preprint Server for Biology
|February 6, 2026
Summary
Researchers developed new CRISPR screening technologies, PORTAL and CAP cloning, to map genetic interactions beyond the genome scale. This enables large-scale, quantitative analysis of gene function in human cells.
Area of Science:
- Genomics
- Molecular Biology
- Biotechnology
Background:
- CRISPR screens are vital for gene function studies but face limitations in scale and scope.
- Probing regulatory elements, genetic variants, and interactions requires enhanced sensitivity and scalability.
Purpose of the Study:
- To overcome limitations of current CRISPR screening methods.
- To enable large-scale, quantitative genetic interaction mapping beyond the genome scale.
Main Methods:
- Introduced PORTAL (Perturbation Output via Reporter Transcriptional Activity in Lineages) for quantitative RNA phenotypes.
- Developed CAP cloning (Covalently closed Assembly Products) for ultrahigh-complexity lentiviral libraries.
- Combined PORTAL and CAP cloning for comprehensive genetic interaction mapping.
Main Results:
- Constructed the largest exhaustive genetic interaction map in human cells to date.
- Mapped 665,856 pairwise perturbations across 46 million clonal lineages.
- Utilized a non-fitness phenotype for large-scale genetic interaction analysis.
Conclusions:
- The developed technologies significantly advance the scale and scope of genetic interaction mapping.
- This work paves the way for comprehensive genetic interaction analysis in human cells.
- Enables deeper understanding of gene function in basic biology and drug discovery.
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