CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
| Autor: | Wing Hung Wong, Yanxia Liu, Xueqiu Lin, Zhixiang Lin, Lei S. Qi, Timothy Daley |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Local fdr lcsh:QH426-470 Method Computational biology Biology Key issues CRISPR screen 03 medical and health sciences Databases Genetic Null distribution CRISPR Clustered Regularly Interspaced Short Palindromic Repeats Computer Simulation Genetic Testing CRISPR interference lcsh:QH301-705.5 Genes Essential Models Genetic CRISPR activation Bayes Theorem Mixture model lcsh:Genetics 030104 developmental biology ROC Curve lcsh:Biology (General) Area Under Curve sgRNA design Mixture models Algorithms RNA Guide Kinetoplastida |
| Zdroj: | Genome Biology, Vol 19, Iss 1, Pp 1-13 (2018) Genome Biology |
| Popis: | 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. Electronic supplementary material The online version of this article (10.1186/s13059-018-1538-6) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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