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Bioinformatics. 2016 Jan 15;32(2):260-7. doi: 10.1093/bioinformatics/btv556. Epub 2015 Sep 28.

ScreenBEAM: a novel meta-analysis algorithm for functional genomics screens via Bayesian hierarchical modeling.

Author information

1
Department of Biomedical Informatics, Department of Systems Biology, Center for Computational Biology and Bioinformatics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA and.
2
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Abstract

MOTIVATION:

Functional genomics (FG) screens, using RNAi or CRISPR technology, have become a standard tool for systematic, genome-wide loss-of-function studies for therapeutic target discovery. As in many large-scale assays, however, off-target effects, variable reagents' potency and experimental noise must be accounted for appropriately control for false positives. Indeed, rigorous statistical analysis of high-throughput FG screening data remains challenging, particularly when integrative analyses are used to combine multiple sh/sgRNAs targeting the same gene in the library.

METHOD:

We use large RNAi and CRISPR repositories that are publicly available to evaluate a novel meta-analysis approach for FG screens via Bayesian hierarchical modeling, Screening Bayesian Evaluation and Analysis Method (ScreenBEAM).

RESULTS:

Results from our analysis show that the proposed strategy, which seamlessly combines all available data, robustly outperforms classical algorithms developed for microarray data sets as well as recent approaches designed for next generation sequencing technologies. Remarkably, the ScreenBEAM algorithm works well even when the quality of FG screens is relatively low, which accounts for about 80-95% of the public datasets.

AVAILABILITY AND IMPLEMENTATION:

R package and source code are available at: https://github.com/jyyu/ScreenBEAM.

CONTACT:

ac2248@columbia.edu, jose.silva@mssm.edu, yujiyang@gmail.com

SUPPLEMENTARY INFORMATION:

Supplementary data are available at Bioinformatics online.

PMID:
26415723
PMCID:
PMC4907394
DOI:
10.1093/bioinformatics/btv556
[Indexed for MEDLINE]
Free PMC Article

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