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.
journal_name
Genome Bioljournal_title
Genome biologyauthors
Daley TP,Lin Z,Lin X,Liu Y,Wong WH,Qi LSdoi
10.1186/s13059-018-1538-6subject
Has Abstractpub_date
2018-10-08 00:00:00pages
159issue
1eissn
1474-7596issn
1474-760Xpii
10.1186/s13059-018-1538-6journal_volume
19pub_type
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