Pooled CRISPR screens are a powerful tool to probe genotype-phenotype relationships at genome-wide scale. However, criteria for optimal design are missing, and it remains unclear how experimental parameters affect results. Here, we report that random decreases in gRNA abundance are more likely than increases due to bottle-neck effects during the cell proliferation phase. Failure to consider this asymmetry leads to loss of detection power. We provide a new statistical test that addresses this problem and improves hit detection at reduced experiment size. The method is implemented in the R package gscreend, which is available at http://bioconductor.org/packages/gscreend .

中文翻译：

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gscreend：在 CRISPR 筛选中对不对称计数比进行建模，以减少实验规模并改善表型检测


混合 CRISPR 筛选是在全基因组范围内探索基因型-表型关系的强大工具。然而，缺少最佳设计的标准，并且尚不清楚实验参数如何影响结果。在这里，我们报告说，由于细胞增殖阶段的瓶颈效应，gRNA 丰度的随机减少比增加的可能性更大。不考虑这种不对称性会导致检测能力的丧失。我们提供了一种新的统计测试来解决这个问题，并在减少实验规模的情况下改进命中检测。该方法在 R 包 gscreend 中实现，可从 http://bioconductor.org/packages/gscreend 获取。