siRNA off-target effects in genome-wide screens identify signaling pathway members

• Published in: Scientific reports Vol. 2; no. 1; p. 428
• Main Authors: Buehler, Eugen, Khan, Aly A., Marine, Shane, Rajaram, Misha, Bahl, Amit, Burchard, Julja, Ferrer, Marc
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.05.2012; Nature Publishing Group
• Subjects: 3' Untranslated Regions - genetics; 631/114; 631/208/505; 631/553; Algorithms; Animals; Base Sequence; Biology; Computational Biology - methods; Datasets; Gene expression; Gene Expression Profiling; Gene Library; Genetic screening; Genome - genetics; Genomes; Genomics - methods; Humanities and Social Sciences; Humans; Models, Genetic; multidisciplinary; Reproducibility of Results; RNA Interference; RNA, Small Interfering - genetics; Science; Signal transduction; Signal Transduction - genetics; siRNA; Wnt protein; Wnt Signaling Pathway - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep00428

We introduce a method for analyzing small interfering RNA (siRNA) genetic screens based entirely on off-target effects. Using a screen for members of the Wnt pathway, we demonstrate that this method identifies known pathway components, some of which are not present in the screening library. This technique can be applied to siRNA screen results retroactively to confirm positives and identify genes missed using conventional methods for on-target gene selection.