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Commentary
Nature Methods - 3, 777 - 779 (2006)
doi:10.1038/nmeth1006-777

Minimizing the risk of reporting false positives in large-scale RNAi screens

Christophe J Echeverri1, Philip A Beachy2, Buzz Baum3, Michael Boutros4, Frank Buchholz5, Sumit K Chanda6, Julian Downward7, Jan Ellenberg8, Andrew G Fraser9, Nir Hacohen10, 11, William C Hahn10, 12, Aimee L Jackson13, Amy Kiger14, Peter S Linsley13, Lawrence Lum15, Yong Ma2, Bernard Mathey-Prévôt16, David E Root8, David M Sabatini8, 17, Jussi Taipale18, Norbert Perrimon16, 19 & René Bernards20

1  Cenix BioScience GmbH, Tatzberg 47, Dresden, 10307, Germany. echeverri@cenix-bioscience.com

2  Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

3  Morphogenesis Group, Ludwig Institute for Cancer Research UCL Branch, Courtauld Building, 91 Riding House Street, London, W1W 7BS, UK.

4  Signaling and Functional Genomics, German Cancer Research Center (DKFZ/B110), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany.

5  Max Plank Institute of Molecular Cell Biology and Genetics, 108 Pfotenhauerstrasse, 01307 Dresden, Germany.

6  Division of Cellular Genomics, The Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, California 92121, USA.

7  Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

8  Gene Expression Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.

9  The Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK.

10  Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.

11  Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital Boston, 55 Fruit Street, Massachusetts 02114, USA.

12  Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.

13  Rosetta Inpharmatics, 401 Terry Ave. N, Seattle, Washington 98109, USA.

14  Department of Cell and Developmental Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.

15  Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd. Dallas, Texas 75390, USA.

16  Drosophila RNAi Screening Center and Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.

17  Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.

18  Molecular and Cancer Biology Program, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014 University of Helsinki, Finland.

19  Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.

20  Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. r.bernards@nki.nl

Large-scale RNA interference (RNAi)-based analyses, very much as other 'omic' approaches, have inherent rates of false positives and negatives. The variability in the standards of care applied to validate results from these studies, if left unchecked, could eventually begin to undermine the credibility of RNAi as a powerful functional approach. This Commentary is an invitation to an open discussion started among various users of RNAi to set forth accepted standards that would insure the quality and accuracy of information in the large datasets coming out of genome-scale screens.

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Nature Methods
ISSN: 1548-7091
EISSN: 1548-7105
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