Nucleic Acids Research Advance Access published online on April 10, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm088
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Methods Online |
Comparison of approaches for rational siRNA design leading to a new efficient and transparent method
1Department of Human Genetics, University of Utah, Salt Lake City 84112-5330, USA, 2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Ul. Vavilova 32, 119991 Moscow, Russia, 3Department of Computer and Information Science, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway, 4National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20894, USA and 5Bioscience Institute, University College Cork, Cork, Ireland
*To whom correspondence should be addressed. Tel: +1-801 5815192; Fax: +1-801 5853910; Email: omatveev{at}genetics.utah.edu
Received January 12, 2007. Accepted January 31, 2007.
Current literature describes several methods for the design of efficient siRNAs with 19 perfectly matched base pairs and 2 nt overhangs. Using four independent databases totaling 3336 experimentally verified siRNAs, we compared how well several of these methods predict siRNA cleavage efficiency. According to receiver operating characteristics (ROC) and correlation analyses, the best programs were BioPredsi, ThermoComposition and DSIR. We also studied individual parameters that significantly and consistently correlated with siRNA efficacy in different databases. As a result of this work we developed a new method which utilizes linear regression fitting with local duplex stability, nucleotide position-dependent preferences and total G/C content of siRNA duplexes as input parameters. The new method's discrimination ability of efficient and inefficient siRNAs is comparable with that of the best methods identified, but its parameters are more obviously related to the mechanisms of siRNA action in comparison with BioPredsi. This permits insight to the underlying physical features and relative importance of the parameters. The new method of predicting siRNA efficiency is faster than that of ThermoComposition because it does not employ time-consuming RNA secondary structure calculations and has much less parameters than DSIR. It is available as a web tool called ‘siRNA scales’.
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