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

被引:51
作者
Buehler, Eugen [1 ]
Khan, Aly A. [2 ]
Marine, Shane [3 ]
Rajaram, Misha [4 ]
Bahl, Amit [5 ]
Burchard, Julja [5 ]
Ferrer, Marc [1 ]
机构
[1] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA
[2] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10065 USA
[3] Merck Res Labs, N Wales, PA 19454 USA
[4] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[5] Merck & Co Inc, West Point, PA 19486 USA
基金
美国国家卫生研究院;
关键词
GENES;
D O I
10.1038/srep00428
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页数:6
相关论文
共 25 条
[1]
NCBI GEO: archive for high-throughput functional genomic data [J].
Barrett, Tanya ;
Troup, Dennis B. ;
Wilhite, Stephen E. ;
Ledoux, Pierre ;
Rudnev, Dmitry ;
Evangelista, Carlos ;
Kim, Irene F. ;
Soboleva, Alexandra ;
Tomashevsky, Maxim ;
Marshall, Kimberly A. ;
Phillippy, Katherine H. ;
Sherman, Patti M. ;
Muertter, Rolf N. ;
Edgar, Ron .
NUCLEIC ACIDS RESEARCH, 2009, 37 :D885-D890
[2]
3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets [J].
Birmingham, A ;
Anderson, EM ;
Reynolds, A ;
Ilsley-Tyree, D ;
Leake, D ;
Fedorov, Y ;
Baskerville, S ;
Maksimova, E ;
Robinson, K ;
Karpilow, J ;
Marshall, WS ;
Khvorova, A .
NATURE METHODS, 2006, 3 (03) :199-204
[3]
Computational aspects of nonparametric smoothing with illustrations from the sm library [J].
Bowman, AW ;
Azzalini, A .
COMPUTATIONAL STATISTICS & DATA ANALYSIS, 2003, 42 (04) :545-560
[4]
Targeting Brn-3b in breast cancer therapy [J].
Budhram-Mahadeo, VS ;
Latchman, DS .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2006, 10 (01) :15-25
[5]
Minimizing the risk of reporting false positives in large-scale RNAi screens [J].
Echeverri, Christophe J. ;
Beachy, Philip A. ;
Baum, Buzz ;
Boutros, Michael ;
Buchholz, Frank ;
Chanda, Sumit K. ;
Downward, Julian ;
Ellenberg, Jan ;
Fraser, Andrew G. ;
Hacohen, Nir ;
Hahn, William C. ;
Jackson, Aimee L. ;
Kiger, Amy ;
Linsley, Peter S. ;
Lum, Lawrence ;
Ma, Yong ;
Mathey-Prevot, Bernard ;
Root, David E. ;
Sabatini, David M. ;
Taipale, Jussi ;
Perrimon, Norbert ;
Bernards, Rene .
NATURE METHODS, 2006, 3 (10) :777-779
[6]
Computational methods to identify miRNA targets [J].
Hammell, Molly .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2010, 21 (07) :738-744
[7]
Widespread siRNA "off-target'' transcript silencing mediated by seed region sequence complementarity [J].
Jackson, Aimee L. ;
Burchard, Julja ;
Schelter, Janell ;
Chau, B. Nelson ;
Cleary, Michele ;
Lim, Lee ;
Linsley, Peter S. .
RNA, 2006, 12 (07) :1179-1187
[8]
Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application [J].
Jackson, Aimee L. ;
Linsley, Peter S. .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (01) :57-67
[9]
KEGG for representation and analysis of molecular networks involving diseases and drugs [J].
Kanehisa, Minoru ;
Goto, Susumu ;
Furumichi, Miho ;
Tanabe, Mao ;
Hirakawa, Mika .
NUCLEIC ACIDS RESEARCH, 2010, 38 :D355-D360
[10]
The UCSC Table Browser data retrieval tool [J].
Karolchik, D ;
Hinrichs, AS ;
Furey, TS ;
Roskin, KM ;
Sugnet, CW ;
Haussler, D ;
Kent, WJ .
NUCLEIC ACIDS RESEARCH, 2004, 32 :D493-D496