Comparison of approaches for rational siRNA design leading to a new efficient and transparent method
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Date
2007
Authors
Matveeva, Olga
Nechipurenko, Yury
Rossi, Leo
Moore, Barry
Saetrom, Pal
Ogurtsov, Aleksey Y.
Atkins, John F.
Shabalina, Svetlana A.
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University Press
Published Version
Abstract
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'.
Description
Keywords
Artificial neural network , RNA interference , Thermodynamic parameters , Functional siRNAs , Dangling ends , Base pairs , Prediction , Selection , Sequences , Efficacy
Citation
Matveeva, O., Nechipurenko, Y., Rossi, L., Moore, B., Sætrom, P., Ogurtsov, A. Y., Atkins, J. F. and Shabalina, S. A. (2007) 'Comparison of approaches for rational siRNA design leading to a new efficient and transparent method', Nucleic Acids Research, 35(8), e63 (10pp.) doi: 10.1093/nar/gkm088