Rapid creation and quantitative monitoring of high coverage shRNA libraries.

Posted by mmcmanus | Created: 09 Jun 2009 | Last Modified: 15 Jun 2009
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Authors: 
Bassik MC[1], Lebbink RJ[1], Churchman LS, Ingolia NT, Patena W, Leproust EM, Schuldiner M, Weissman JS, McManus MT.
Journal: 
Nat Methods
Publication Date: 
May 17, 2009
Institutions: 
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, USA. [1] These authors contributed equally to this work.
Abstract: 
Short hairpin RNA libraries are limited by low efficacy of many shRNAs and by off-target effects, which give rise to false negatives and false positives, respectively. Here we present a strategy for rapidly creating expanded shRNA pools ( approximately 30 shRNAs per gene) that are analyzed by deep sequencing (EXPAND). This approach enables identification of multiple effective target-specific shRNAs from a complex pool, allowing a rigorous statistical evaluation of true hits.