On Jan. 27, 2025, researchers at the Broad Institute of MIT and Harvard, along with collaborators at Calico Life Sciences, announced they have developed an approach that brings the power of microscopy imaging to genome-scale CRISPR screens in a scalable way.

Visualizing cells after editing specific genes can help scientists learn new details about the function of those genes. To accomplish this the researchers used PERISCOPE, a technique for genome-wide imaging screens that helps Broad scientists understand the connections between genes and traits.

PERISCOPE — which stands for perturbation effect readout in situ via single-cell optical phenotyping — combines two technologies developed by Broad scientists: Cell Painting, which can capture images and key measures of subcellular compartments at scale, and Optical Pooled Screening, which “barcodes” cells and uses CRISPR to systematically turn off individual genes to study their function in those cells. 

The new technique lets scientists study the effects of perturbing over 20,000 genes on hundreds of image-based cellular features. Generating data with the method is more than 10 times less expensive than comparable high-dimensional approaches such as high-throughput single-cell RNA sequencing and can be adapted to study a wide variety of cell types.

In Nature Methods, the researchers applied PERISCOPE to execute three whole-genome CRISPR screens to create an open-source atlas of cell morphology.