Skip Navigation



Bioinformatics Advance Access published online on November 25, 2004
Bioinformatics, doi:10.1093/bioinformatics/bti155
Bioinformatics © Oxford University Press 2004; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
21/8/1316    most recent
bti155v2
bti155v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Yamada, T.
Right arrow Articles by Morishita, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamada, T.
Right arrow Articles by Morishita, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received September 15, 2004
Revised November 4, 2004
Accepted November 12, 2004

Article

Accelerated off-target search algorithm for siRNA

Tomoyuki Yamada 1* and Shinichi Morishita 1

1 Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo

* To whom correspondence should be addressed.
Tomoyuki Yamada, E-mail: yamada{at}cb.k.u-tokyo.ac.jp


  Abstract

Motivation: Designing highly effective siRNA sequences with maximum target-specificity for mammalian RNA interference (RNAi) is one of the hottest topics in molecular biology. The relationship between siRNA sequences and RNAi activity has been studied extensively to establish rules for selecting highly effective sequences. However, there is a pressing need to compute siRNA sequences that minimize off-target silencing effects efficiently and to match any non-targeted sequences with mismatches.

Results: The enumeration of potential cross-hybridization candidates is non-trivial, because siRNA sequences are short, ca. 19 nt in length, and at least three mismatches with non-targets are required. With at least three mismatches, there are typically four or five contiguous matches, so that a BLAST search frequently overlooks off-target candidates. By contrast, existing accurate approaches are expensive to execute; thus we need to develop an accurate, efficient algorithm that uses seed hashing, the pigeonhole principle, and combinatorics to identify mismatch patterns. Tests show that our method can list potential cross-hybridization candidates for any siRNA sequence of selected human gene rapidly, outperforming traditional methods by orders of magnitude in terms of computational performance.

Availability: http://design.RNAi.jp.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
Y.-K. Park, S.-M. Park, Y.-C. Choi, D. Lee, M. Won, and Y. J. Kim
AsiDesigner: exon-based siRNA design server considering alternative splicing
Nucleic Acids Res., July 1, 2008; 36(suppl_2): W97 - W103.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
P. R. Clark, J. S. Pober, and M. S. Kluger
Knockdown of TNFR1 by the sense strand of an ICAM-1 siRNA: dissection of an off-target effect
Nucleic Acids Res., March 27, 2008; 36(4): 1081 - 1097.
[Abstract] [Full Text] [PDF]

Home page
 Brief Funct Genomic ProteomicHome page
A. Jagannath and M. Wood
RNA interference based gene therapy for neurological disease
Brief Funct Genomic Proteomic, May 3, 2007; (2007) elm005v1.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Y. Naito, K. Ui-Tei, T. Nishikawa, Y. Takebe, and K. Saigo
siVirus: web-based antiviral siRNA design software for highly divergent viral sequences.
Nucleic Acids Res., July 1, 2006; 34(Web Server issue): W448 - W450.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T. Yamada, H. Soma, and S. Morishita
PrimerStation: a highly specific multiplex genomic PCR primer design server for the human genome.
Nucleic Acids Res., July 1, 2006; 34(Web Server issue): W665 - W669.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Y. Naito, T. Yamada, T. Matsumiya, K. Ui-Tei, K. Saigo, and S. Morishita
dsCheck: highly sensitive off-target search software for double-stranded RNA-mediated RNA interference
Nucleic Acids Res., July 1, 2005; 33(suppl_2): W589 - W591.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.