gespeR: a statistical model for deconvoluting off-target-confounded RNA interference screens

被引：30

作者：

Schmich, Fabian ^{[1
,2
]}

Szczurek, Ewa ^{[1
,2
]}

Kreibich, Saskia ^{[3
]}

Dilling, Sabrina ^{[3
]}

Andritschke, Daniel ^{[3
]}

Casanova, Alain ^{[4
]}

Low, Shyan Huey ^{[4
]}

Eicher, Simone ^{[4
]}

Muntwiler, Simone ^{[4
]}

Emmenlauer, Mario ^{[4
]}

Raemoe, Pauli ^{[4
]}

Conde-Alvarez, Raquel ^{[5
,6
]}

von Mering, Christian ^{[2
,7
]}

Hardt, Wolf-Dietrich ^{[3
]}

Dehio, Christoph ^{[4
]}

Beerenwinkel, Niko ^{[1
,2
]}

机构：

[1] ETH, Dept Biosyst Sci & Engn, Zurich, Switzerland

[2] SIB, Lausanne, Switzerland

[3] ETH, Dept Biol, Zurich, Switzerland

[4] Univ Basel, Biozentrum, Basel, Switzerland

[5] Univ Navarra, Inst Trop Hlth, E-31080 Pamplona, Spain

[6] Univ Navarra, Dept Microbiol & Parasitol, E-31080 Pamplona, Spain

[7] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland

来源：

GENOME BIOLOGY | 2015年 / 16卷

关键词：

RNAi; siRNA; Off-target; Confounded; Phenotype; Deconvolution; Statistical model; Hit prioritization; Pathogen infection screen; SELECTION; STABILITY; REVEALS; GTPASES; SIRNAS; TOOL;

D O I：

10.1186/s13059-015-0783-1

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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-beta signaling. gespeR is available as a Bioconductor R-package.

引用

页数：12

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