Complementary human gene interaction maps from radiation hybrids and CRISPRi

The only comprehensive genetic interaction map of the human genome was constructed using increased gene copy number in radiation hybrid (RH) cells. More recently, interactions restricted to essential genes were identified using loss-of-function alleles made by CRISPRi technology. I compared the two maps to understand their similarities and differences. Both maps overlapped significantly with a database of protein-protein interactions. However, interactions in the RH and CRISPRi datasets had no significant overlap, even though the participating genes overlapped significantly. In addition, the RH map showed highly significant similarity with an interaction map constructed from genome-wide association studies (GWASs), while the CRISPRi map did not. This study reveals that gain- and loss-of-function alleles highlight different aspects of the genetic interaction landscape.本研究通过在辐射杂交（radiation hybrid, RH）细胞中提升基因拷贝数，构建了目前唯一的人类基因组综合遗传相互作用图谱。近期，研究人员借助CRISPR干扰（CRISPRi）技术构建的功能丧失等位基因，鉴定出了仅限定于必需基因的遗传相互作用。本研究对这两份图谱开展对比分析，以厘清二者的异同。两份图谱均与蛋白质-蛋白质相互作用数据库存在显著重合，但即便二者涉及的基因存在显著重叠，RH数据集与CRISPRi数据集的遗传相互作用却未呈现出显著重合。此外，RH图谱与基于全基因组关联研究（genome-wide association studies, GWAS）构建的相互作用图谱具有高度显著的相似性，而CRISPRi图谱则无此特征。本研究表明，功能获得等位基因与功能丧失等位基因分别展现了遗传相互作用全景的不同维度。