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Next-generation forward genetic screens: uniting high-throughput perturbations with single-cell analysis
John A Morris1, Jennifer S Sun1, Neville E Sanjana1
1New York Genome Center, New York, NY 10013, USA; Department of Biology, New York University, New York, NY 10003, USA.
Trends in Genetics : TIG
|November 21, 2023
Summary
CRISPR screens now integrate with single-cell multiomics to reveal how genetic changes affect cellular states. This powerful combination advances understanding of gene function and disease mechanisms in biomedical science.
Area of Science:
- Biomedical Science
- Genomics
- Molecular Biology
Background:
- Programmable genome engineering technologies like CRISPR have revolutionized biomedical research.
- CRISPR screens link genes to disease-relevant phenotypes but were previously limited to single-cell readouts.
- Advances are needed to understand complex genetic perturbation effects on cellular states.
Purpose of the Study:
- To review technologies pairing CRISPR screens with single-cell multiomics.
- To highlight opportunities in extending pooled screens with deep multimodal phenotyping.
- To showcase the impact of genetic perturbations on cellular transcriptome, proteome, and epigenome.
Main Methods:
- Pairing massively parallel CRISPR screens with high-dimensional single-cell profiling.
- Utilizing single-cell multiomics to measure cellular responses to genetic perturbations.
- Extending pooled screens with deep multimodal phenotyping.
Main Results:
- CRISPR screens can now be coupled with single-cell multiomics for comprehensive analysis.
- This approach enables measurement of transcriptome, proteome, and epigenome changes.
- Individual and combinatorial genetic perturbations can be assessed at single-cell resolution.
Conclusions:
- The integration of CRISPR screens and single-cell multiomics offers unprecedented insights into gene function.
- This powerful combination expands the scope of genetic screens to complex cellular phenotypes.
- Future research can leverage these technologies to deepen understanding of disease biology.
