The Power Decoder Simulator for the Evaluation of Pooled shRNA Screen Performance

Journal of Biomolecular Screening
Jesse StombaughAnnaleen Vermeulen

Abstract

RNA interference screening using pooled, short hairpin RNA (shRNA) is a powerful, high-throughput tool for determining the biological relevance of genes for a phenotype. Assessing an shRNA pooled screen's performance is difficult in practice; one can estimate the performance only by using reproducibility as a proxy for power or by employing a large number of validated positive and negative controls. Here, we develop an open-source software tool, the Power Decoder simulator, for generating shRNA pooled screening experiments in silico that can be used to estimate a screen's statistical power. Using the negative binomial distribution, it models both the relative abundance of multiple shRNAs within a single screening replicate and the biological noise between replicates for each individual shRNA. We demonstrate that this simulator can successfully model the data from an actual laboratory experiment. We then use it to evaluate the effects of biological replicates and sequencing counts on the performance of a pooled screen, without the necessity of gathering additional data. The Power Decoder simulator is written in R and Python and is available for download under the GNU General Public License v3.0.

References

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Citations

Aug 21, 2015·Journal of Biomolecular Screening·Marc BickleLorenz Martin Mayr
Jul 25, 2017·BMC Bioinformatics·Tamas Nagy, Martin Kampmann

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Methods Mentioned

BETA
PCR
Illumina sequencing
gene knockout

Software Mentioned

DESeq
R
Power Decoder simulator
Bowtie
simulate
vary
Power Decoder
Python
experiment
PyCogent

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