Haploid genetic screens identify key regulators of protein phenotypes and signaling transduction

Genome-wide genetic screen has been a powerful system to study the regulation of a variety of signaling pathways, expression and essentiality of genes, and targeted therapy resistance mechanisms in human cells, especially cancer cells (1-5). However, the direct connection between genomic mutations and the regulation of protein states remains elusive. In a recent paper published in Nature, Brockmann and colleagues utilized gene-trap mutagenesis approach coupled with antibody staining for proteins of interest to execute a series of genetic screens in human haploid HAP1 cells, aiming to investigate the direct link between genomic perturbations and specific protein phenotypes (6).