title: gespeR: a statistical model for deconvoluting off-target-confounded RNA interference screens.
abstract: Small interfering RNAs (siRNAs) exhibit strong off-target effects, which confound the gene-level interpretation of RNA interference screens and thus limit their utility for functional genomics studies. Here, we present gespeR, a statistical model for reconstructing individual, gene-specific phenotypes. Using 115,878 siRNAs, single and pooled, from three companies in three pathogen infection screens, we demonstrate that deconvolution of image-based phenotypes substantially improves the reproducibility between independent siRNA sets targeting the same genes. Genes selected and prioritized by gespeR are validated and shown to constitute biologically relevant components of pathogen entry mechanisms and TGF-β signaling. gespeR is available as a Bioconductor R-package.
authors.affiliation: Department of Biosystems Science and Engineering, ETH, Zurich, Switzerland. fabian.schmich@bsse.ethz.ch.|SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. fabian.schmich@bsse.ethz.ch.
authors.forename: Fabian
authors.initials: F
authors.lastname: Schmich
authors.affiliation: Department of Biosystems Science and Engineering, ETH, Zurich, Switzerland. ewa.szczurek@bsse.ethz.ch.|SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. ewa.szczurek@bsse.ethz.ch.
authors.forename: Ewa
authors.initials: E
authors.lastname: Szczurek
authors.affiliation: Department of Biology, ETH, Zurich, Switzerland. saskia.kreibich@micro.biol.ethz.ch.
authors.forename: Saskia
authors.initials: S
authors.lastname: Kreibich
authors.affiliation: Department of Biology, ETH, Zurich, Switzerland. sabrina.dilling@micro.biol.ethz.ch.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dilling
authors.affiliation: Department of Biology, ETH, Zurich, Switzerland. daniel.andritschke@micro.biol.ethz.ch.
authors.forename: Daniel
authors.initials: D
authors.lastname: Andritschke
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland. alain.casanova@unibas.ch.
authors.forename: Alain
authors.initials: A
authors.lastname: Casanova
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland. shyan.low@unibas.ch.
authors.forename: Shyan Huey
authors.initials: SH
authors.lastname: Low
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland. simone.eicher@unibas.ch.
authors.forename: Simone
authors.initials: S
authors.lastname: Eicher
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland. simone.muntwiler@unibas.ch.
authors.forename: Simone
authors.initials: S
authors.lastname: Muntwiler
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland. mario.emmenlauer@unibas.ch.
authors.forename: Mario
authors.initials: M
authors.lastname: Emmenlauer
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland. pauli.ramo@unibas.ch.
authors.forename: Pauli
authors.initials: P
authors.lastname: Rämö
authors.affiliation: Institute for Tropical Health and Departamento de Microbiología y Parasitología, Universidad de Navarra, Pamplona, Spain. rconde@unav.es.
authors.forename: Raquel
authors.initials: R
authors.lastname: Conde-Alvarez
authors.affiliation: SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. mering@imls.uzh.ch.|Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland. mering@imls.uzh.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: von Mering
authors.affiliation: Department of Biology, ETH, Zurich, Switzerland. wolf-dietrich.hardt@micro.biol.ethz.ch.
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Hardt
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland. christoph.dehio@unibas.ch.
authors.forename: Christoph
authors.initials: C
authors.lastname: Dehio
authors.affiliation: Department of Biosystems Science and Engineering, ETH, Zurich, Switzerland. niko.beerenwinkel@bsse.ethz.ch.|SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. niko.beerenwinkel@bsse.ethz.ch.
authors.forename: Niko
authors.initials: N
authors.lastname: Beerenwinkel
mesh_terms: D018416:Bartonella henselae / Q000235:genetics; D002003:Brucella abortus / Q000235:genetics; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D015233:Models, Statistical; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering; D012486:Salmonella typhimurium / Q000235:genetics; D015398:Signal Transduction; D012984:Software; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta