CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens

Genome Biology

Lei S. Qi¹  Yanxia Liu¹  Xueqiu Lin¹  Zhixiang Lin²  Timothy P. Daley²  Wing Hung Wong² 

[1] Department of Bioengineering, Stanford University;Department of Statistics, Stanford University;

关键词: CRISPR screen;    CRISPR interference;    CRISPR activation;    sgRNA design;    Mixture models;    Local fdr;   

DOI  :  10.1186/s13059-018-1538-6

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown