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Vol 42(2008) N 1 p. 146-152;
T. Alsheddi1,6, L. Vasin2, R. Meduri1,3, M. Randhawa3, G. Glazko4, A. Baranova3,5

siRNAs with high specificity to a target: A systematic design by the CRM algorithm

1School of Computational Sciences, George Mason University, Fairfax, VA, 22030, USA
2Information and Calculation Center, Penza State University of Architecture and Construction, Penza, 440026, Russia
3Molecular and Microbiology Department, College of Science, George Mason University, Fairfax, VA, 22030, USA
4Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA
5Medical Genetic Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia
6National Guard Hospital Research Center, Riyadh, Saudi Arabia
Received - 2007-05-23; Accepted - 2007-07-05

The "off-target" silencing effect hinders the development of siRNA-based therapeutic and research applications. A common solution to this problem is an employment of BLAST, which may miss significant alignments, or an exhaustive Smith-Waterman algorithm, which is very time-consuming. A Comprehensive Redundancy Minimizer (CRM) approach was developed for mapping all unique sequences ("targets") 9-15 nt in size within large sets of sequences (e.g., transcriptomes). CRM outputs a list of potential siRNA candidates for every transcript of a particular species. These candidates could be further analyzed by traditional "set-ofrules" types of siRNA designing tools. For human, 91% of transcripts are covered by candidate siRNAs with kernel targets of 15 nt. The approach was tested with a collection of previously described experimentally assessed siRNAs, and a significant correlation was found between the efficacy and presence in the CRMapproved set (r = 0.215, p-value = 0.0001). An interactive database containing a precompiled set of all human siRNA candidates with minimized redundancy is available at http://129.174.194.243. Application of the CRMbased filtering minimizes potential off-target silencing effects and could improve routine siRNA applications.

siRNA, precomputed database, off-target effects, Comprehensive Redundancy Minimizer



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