CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
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DOI：
10.1186/s13059-018-1538-6
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发表时间：
2018-10-08
期刊：
影响因子：
12.3
通讯作者：
Qi, Lei S.
中科院分区：
文献类型：
--
作者：
Daley, Timothy P.;Lin, Zhixiang;Qi, Lei S.
集合CRISPR筛选使研究人员能够在全基因组范围内询问复杂表型的遗传原因，并承诺与竞争技术相比具有更高的特异性和敏感性。不幸的是，存在两个问题，特别是对于CRISPRi/a屏幕：导轨效率的可变性和大的罕见的偏离目标的效果。我们提出了一种方法CRISPhieRMix，它通过使用具有宽尾零分布的分层混合模型来解决这些问题。我们表明，CRISPhieRMix允许在大规模池CRISPRi/a屏幕上进行更准确和更强大的推断。我们讨论了屏幕分析和设计中的关键问题，特别是忠实地全面发现所需的向导数量。
Pooled CRISPR screens allow researchers to interrogate genetic causes of complex phenotypes at the genome-wide scale and promise higher specificity and sensitivity compared to competing technologies. Unfortunately, two problems exist, particularly for CRISPRi/a screens: variability in guide efficiency and large rare off-target effects. We present a method, CRISPhieRmix, that resolves these issues by using a hierarchical mixture model with a broad-tailed null distribution. We show that CRISPhieRmix allows for more accurate and powerful inferences in large-scale pooled CRISPRi/a screens. We discuss key issues in the analysis and design of screens, particularly the number of guides needed for faithful full discovery.