The article introduces a novel, cost-effective method called "compressed Perturb-seq" for large-scale genetic screening of regulatory circuits. This technique modifies the conventional Perturb-seq method by employing algorithmic compressed sensing principles, allowing for measurement of random combinations of genetic perturbations (either through "cell-pooling" or "guide-pooling") and subsequent computational decompression using a new inference method, FR-Perturb. The authors demonstrate that compressed Perturb-seq achieves accuracy comparable to conventional methods while offering substantial reductions in cost and cell count, with guide-pooling specifically enhancing the ability to detect second-order genetic interactions. The study applies this framework to analyze the regulatory circuitry of the LPS response in human macrophage cells, identifying both known and novel immune regulators and integrating findings with human disease data from GWAS and eQTL studies.

References:

• Yao D, Binan L, Bezney J, et al. Scalable genetic screening for regulatory circuits using compressed Perturb-seq[J]. Nature biotechnology, 2024, 42(8): 1282-1295.