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  1. Article ; Online: A benchmark of algorithms for the analysis of pooled CRISPR screens

    Sunil Bodapati / Timothy P. Daley / Xueqiu Lin / James Zou / Lei S. Qi

    Genome Biology, Vol 21, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Abstract Genome-wide pooled CRISPR-Cas-mediated knockout, activation, and repression screens are powerful tools for functional genomic investigations. Despite their increasing importance, there is currently little guidance on how to design and analyze ... ...

    Abstract Abstract Genome-wide pooled CRISPR-Cas-mediated knockout, activation, and repression screens are powerful tools for functional genomic investigations. Despite their increasing importance, there is currently little guidance on how to design and analyze CRISPR-pooled screens. Here, we provide a review of the commonly used algorithms in the computational analysis of pooled CRISPR screens. We develop a comprehensive simulation framework to benchmark and compare the performance of these algorithms using both synthetic and real datasets. Our findings inform parameter choices of CRISPR screens and provide guidance to researchers on the design and analysis of pooled CRISPR screens.
    Keywords CRISPR screen ; CRISPR knockoout ; CRISPR interference ; CRISPR activation ; Benchmarking ; Screen algorithms ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: GEMINI

    Mahdi Zamanighomi / Sidharth S. Jain / Takahiro Ito / Debjani Pal / Timothy P. Daley / William R. Sellers

    Genome Biology, Vol 20, Iss 1, Pp 1-

    a variational Bayesian approach to identify genetic interactions from combinatorial CRISPR screens

    2019  Volume 10

    Abstract: Abstract Systems for CRISPR-based combinatorial perturbation of two or more genes are emerging as powerful tools for uncovering genetic interactions. However, systematic identification of these relationships is complicated by sample, reagent, and ... ...

    Abstract Abstract Systems for CRISPR-based combinatorial perturbation of two or more genes are emerging as powerful tools for uncovering genetic interactions. However, systematic identification of these relationships is complicated by sample, reagent, and biological variability. We develop a variational Bayes approach (GEMINI) that jointly analyzes all samples and reagents to identify genetic interactions in pairwise knockout screens. The improved accuracy and scalability of GEMINI enables the systematic analysis of combinatorial CRISPR knockout screens, regardless of design and dimension. GEMINI is available as an open source R package on GitHub at https://github.com/sellerslab/gemini.
    Keywords GEMINI ; CRISPR ; Combinatorial ; Double knockout ; Genetic interactions ; Variational inference ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: CRISPhieRmix

    Timothy P. Daley / Zhixiang Lin / Xueqiu Lin / Yanxia Liu / Wing Hung Wong / Lei S. Qi

    Genome Biology, Vol 19, Iss 1, Pp 1-

    a hierarchical mixture model for CRISPR pooled screens

    2018  Volume 13

    Abstract: 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, ... ...

    Abstract 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.
    Keywords CRISPR screen ; CRISPR interference ; CRISPR activation ; sgRNA design ; Mixture models ; Local fdr ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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