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Explicit Modeling of siRNA-Dependent On- and Off-Target Repression Improves the Interpretation of Screening Results

Riba, Andrea and Emmenlauer, Mario and Chen, Amy and Sigoillot, Frederic and Cong, Feng and Dehio, Christoph and Jenkins, Jeremy and Zavolan, Mihaela. (2017) Explicit Modeling of siRNA-Dependent On- and Off-Target Repression Improves the Interpretation of Screening Results. Cell Systems, 4 (2). pp. 182-193.

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Official URL: http://edoc.unibas.ch/54794/

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Abstract

RNAi is broadly used to map gene regulatory networks, but the identification of genes that are responsible for the observed phenotypes is challenging, as small interfering RNAs (siRNAs) simultaneously downregulate the intended on targets and many partially complementary off targets. Additionally, the scarcity of publicly available control datasets hinders the development and comparative evaluation of computational methods for analyzing the data. Here, we introduce PheLiM (https://github.com/andreariba/PheLiM), a method that uses predictions of siRNA on- and off-target downregulation to infer gene-specific contributions to phenotypes. To assess the performance of PheLiM, we carried out siRNA- and CRISPR/Cas9-based genome-wide screening of two well-characterized pathways, bone morphogenetic protein (BMP) and nuclear factor κB (NF-κB), and we reanalyzed publicly available siRNA screens. We demonstrate that PheLiM has the overall highest accuracy and most reproducible results compared to other available methods. PheLiM can accommodate various methods for predicting siRNA off targets and is broadly applicable to the identification of genes underlying complex phenotypes.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Dehio)
UniBasel Contributors:Zavolan, Mihaela and Dehio, Christoph and Riba, Andrea and Emmenlauer, Mario
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:2405-4712
e-ISSN:2405-4720
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:13 Apr 2018 12:31
Deposited On:16 Oct 2017 10:18

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