Complementary human gene interaction maps from radiation hybrids and CRISPRi

The only comprehensive human genetic interaction map was constructed using increased gene copy numbers in radiation hybrid (RH) cells. Recently, a second map restricted to essential genes was created using CRISPR interference (CRISPRi)-induced loss-of-function alleles. Here, the two maps are compared to understand their similarities and differences. Both maps showed significant overlap with protein-protein interaction databases and identified a shared set of interacting genes, although the specific gene pairs differed between approaches. Notably, the RH map exhibited strong overlap with genome-wide association study (GWAS) networks, whereas the CRISPRi map did not. These findings demonstrate how gain- and loss-of-function alleles reveal distinct yet complementary genetic interaction landscapes.NEW & NOTEWORTHY This study compared two mammalian genetic interaction networks for cell growth: the radiation hybrid (RH) network used extra gene copies and the CRISPRi network used partial gene suppression. Both networks overlapped with protein-protein interaction data and identified common interacting genes, yet specific gene pair interactions differed dramatically. Only the RH network predicted genome-wide association study (GWAS) networks. As the first comparison of large-scale mammalian genetic interaction networks, this work reveals how gain- and loss-of-function variants capture diverse biological perspectives.