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The recent advent of genetic tools, such as Peturb-seq, that combine the analysis of pooled CRISPR screens with single-cell RNA sequencing has delivered unprecedented insights into mammalian gene function and genetic regulatory networks. However, current implementations of these tools face technical and practical limitations that restrict their use. To overcome these challenges, Joe Roplogle and researchers at University of California - San Francisco, Princeton University, and 10x Genomics have developed “direct-capture” Peturb-seq, which enables substantially higher throughput investigations into genetic interactions. Furthermore, through the addition of a hybridization-based target enrichment methodology, sensitive and specific sequencing of biologically meaningful panels of transcripts is now possible — significantly reducing experimental costs.