Comparison of approaches for rational siRNA design leading to a new efficient and transparent method

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dc.contributor.author Matveeva, Olga
dc.contributor.author Nechipurenko, Yury
dc.contributor.author Rossi, Leo
dc.contributor.author Moore, Barry
dc.contributor.author Saetrom, Pal
dc.contributor.author Ogurtsov, Aleksey Y.
dc.contributor.author Atkins, John F.
dc.contributor.author Shabalina, Svetlana A.
dc.date.accessioned 2017-11-14T13:24:32Z
dc.date.available 2017-11-14T13:24:32Z
dc.date.issued 2007
dc.identifier.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 en
dc.identifier.volume 35
dc.identifier.issued 8
dc.identifier.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/10468/5032
dc.identifier.doi 10.1093/nar/gkm088
dc.description.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'. en
dc.description.sponsorship National Institutes of Health (SBIR grant R43 HG003355-01; National Center for Biotechnology Information Intramural Research Program); University of Utah (‘Bridge’ and ‘Technology Commercialization’ grants); Russian Academy of Sciences (Presidium program ‘Molecular and cell biology’); Ministry of Education and Science of the Russian Federation (Russian State Grant ‘Construction of new drugs for therapy and prophylaxis of antiviral diseases by methods of organic chemistry’) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Oxford University Press en
dc.relation.uri https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkm088
dc.rights © 2007, the Authors. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/2.0/uk/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. en
dc.rights.uri https://creativecommons.org/licenses/by-nc/2.0/uk/
dc.subject Artificial neural network en
dc.subject RNA interference en
dc.subject Thermodynamic parameters en
dc.subject Functional siRNAs en
dc.subject Dangling ends en
dc.subject Base pairs en
dc.subject Prediction en
dc.subject Selection en
dc.subject Sequences en
dc.subject Efficacy en
dc.title Comparison of approaches for rational siRNA design leading to a new efficient and transparent method en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother John F. Atkins, Biochemistry, University College Cork , Cork, Ireland T: +353-21-490-3000. E: j.atkins@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 726650
dc.contributor.funder National Institutes of Health
dc.contributor.funder University of Utah
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder Russian Academy of Sciences
dc.contributor.funder Ministry of Education and Science of the Russian Federation
dc.description.status Peer reviewed en
dc.identifier.journaltitle Nucleic Acids Research en
dc.internal.IRISemailaddress j.atkins@ucc.ie en
dc.identifier.articleid e63


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© 2007, the Authors. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/2.0/uk/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Except where otherwise noted, this item's license is described as © 2007, the Authors. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/2.0/uk/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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