CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens

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 efficien...

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Autores principales: Daley, Timothy P., Lin, Zhixiang, Lin, Xueqiu, Liu, Yanxia, Wong, Wing Hung, Qi, Lei S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Method
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176515/
https://www.ncbi.nlm.nih.gov/pubmed/30296940
http://dx.doi.org/10.1186/s13059-018-1538-6
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author Daley, Timothy P.
Lin, Zhixiang
Lin, Xueqiu
Liu, Yanxia
Wong, Wing Hung
Qi, Lei S.
author_facet Daley, Timothy P.
Lin, Zhixiang
Lin, Xueqiu
Liu, Yanxia
Wong, Wing Hung
Qi, Lei S.
author_sort Daley, Timothy P.
collection PubMed
description 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.
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spelling pubmed-61765152018-10-18 CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens Daley, Timothy P. Lin, Zhixiang Lin, Xueqiu Liu, Yanxia Wong, Wing Hung Qi, Lei S. Genome Biol Method 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. BioMed Central 2018-10-08 /pmc/articles/PMC6176515/ /pubmed/30296940 http://dx.doi.org/10.1186/s13059-018-1538-6 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Method
Daley, Timothy P.
Lin, Zhixiang
Lin, Xueqiu
Liu, Yanxia
Wong, Wing Hung
Qi, Lei S.
CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
title CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
title_full CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
title_fullStr CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
title_full_unstemmed CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
title_short CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens
title_sort crisphiermix: a hierarchical mixture model for crispr pooled screens
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176515/
https://www.ncbi.nlm.nih.gov/pubmed/30296940
http://dx.doi.org/10.1186/s13059-018-1538-6
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AT liuyanxia crisphiermixahierarchicalmixturemodelforcrisprpooledscreens
AT wongwinghung crisphiermixahierarchicalmixturemodelforcrisprpooledscreens
AT qileis crisphiermixahierarchicalmixturemodelforcrisprpooledscreens

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