We present scMAGeCK, a computational framework to identify genomic elements associated with multiple expression-based phenotypes in CRISPR/Cas9 functional screening that uses single-cell RNA-seq as readout. scMAGeCK outperforms existing methods, identifies genes and enhancers with known and novel functions in cell proliferation, and enables an unbiased construction of genotype-phenotype network. Single-cell CRISPR screening on mouse embryonic stem cells identifies key genes associated with different pluripotency states. Applying scMAGeCK on multiple datasets, we identify key factors that improve the power of single-cell CRISPR screening. Collectively, scMAGeCK is a novel tool to study genotype-phenotype relationships at a single-cell level.

中文翻译：

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scMAGeCK 在单细胞 CRISPR 筛选中将基因型与多种表型联系起来

我们提出了 scMAGeCK，这是一种计算框架，用于在使用单细胞 RNA-seq 作为读数的 CRISPR/Cas9 功能筛选中识别与多种基于表达的表型相关的基因组元件。scMAGeCK 优于现有方法，识别在细胞增殖中具有已知和新功能的基因和增强子，并能够无偏见地构建基因型-表型网络。对小鼠胚胎干细胞的单细胞 CRISPR 筛选确定了与不同多能性状态相关的关键基因。在多个数据集上应用 scMAGeCK，我们确定了提高单细胞 CRISPR 筛选能力的关键因素。总的来说，scMAGeCK 是一种在单细胞水平上研究基因型-表型关系的新工具。