title: The Power Decoder Simulator for the Evaluation of Pooled shRNA Screen Performance.
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.
authors.affiliation: Dharmacon, part of GE Healthcare, Lafayette, CO, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Stombaugh
authors.affiliation: Dharmacon, part of GE Healthcare, Lafayette, CO, USA.
authors.forename: Abel
authors.initials: A
authors.lastname: Licon
authors.affiliation: Dharmacon, part of GE Healthcare, Lafayette, CO, USA.
authors.forename: Žaklina
authors.initials: Ž
authors.lastname: Strezoska
authors.affiliation: Dharmacon, part of GE Healthcare, Lafayette, CO, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Stahl
authors.affiliation: Dharmacon, part of GE Healthcare, Lafayette, CO, USA.
authors.forename: Sarah Bael
authors.initials: SB
authors.lastname: Anderson
authors.affiliation: Dharmacon, part of GE Healthcare, Lafayette, CO, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Banos
authors.affiliation: Dharmacon, part of GE Healthcare, Lafayette, CO, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: van Brabant Smith
authors.affiliation: Dharmacon, part of GE Healthcare, Lafayette, CO, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Birmingham
authors.affiliation: Dharmacon, part of GE Healthcare, Lafayette, CO, USA annaleen.vermeulen@ge.com.
authors.forename: Annaleen
authors.initials: A
authors.lastname: Vermeulen
mesh_terms: D002460:Cell Line; D003198:Computer Simulation; D015723:Gene Library; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008954:Models, Biological; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D015203:Reproducibility of Results; D012984:Software
chemical_list: D034741:RNA, Small Interfering
keywords: Monte Carlo simulations; RNA interference; pooled screening; power analysis; shRNA library