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CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens.

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.

SUBMITTER: Daley TP

PROVIDER: S-EPMC6176515 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens.

Daley Timothy P TP Lin Zhixiang Z Lin Xueqiu X Liu Yanxia Y Wong Wing Hung WH Qi Lei S LS

Genome biology 20181008 1

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 CRISPhieRm ...[more]

PMID: 30296940

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