281-Perturb-seq Maps Genotype-Phenotype Landscapes

Paper Talk · Nov 30, 2025 · 19m

The paper details a comprehensive study employing genome-scale Perturb-seq screens—a technique combining genetic perturbations via CRISPR interference (CRISPRi) with single-cell RNA sequencing (scRNA-seq)—to create detailed genotype-phenotype maps in K562 and RPE1 cell lines. This methodology is shown to be highly effective for the unbiased assignment of gene function and for dissecting complex cellular phenotypes, such as RNA splicing, cell differentiation, and chromosomal instability (CIN). Key discoveries include the functional assignment of poorly characterized genes in processes like…