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

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dc.contributor.authorMatveeva, Olga
dc.contributor.authorNechipurenko, Yury
dc.contributor.authorRossi, Leo
dc.contributor.authorMoore, Barry
dc.contributor.authorSaetrom, Pal
dc.contributor.authorOgurtsov, Aleksey Y.
dc.contributor.authorAtkins, John F.
dc.contributor.authorShabalina, Svetlana A.
dc.contributor.funderNational Institutes of Health
dc.contributor.funderUniversity of Utah
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderRussian Academy of Sciences
dc.contributor.funderMinistry of Education and Science of the Russian Federation
dc.date.accessioned2017-11-14T13:24:32Z
dc.date.available2017-11-14T13:24:32Z
dc.date.issued2007
dc.description.abstractCurrent 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.sponsorshipNational 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.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide63
dc.identifier.citationMatveeva, 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/gkm088en
dc.identifier.doi10.1093/nar/gkm088
dc.identifier.issn0305-1048
dc.identifier.issued8
dc.identifier.journaltitleNucleic Acids Researchen
dc.identifier.urihttps://hdl.handle.net/10468/5032
dc.identifier.volume35
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urihttps://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.urihttps://creativecommons.org/licenses/by-nc/2.0/uk/
dc.subjectArtificial neural networken
dc.subjectRNA interferenceen
dc.subjectThermodynamic parametersen
dc.subjectFunctional siRNAsen
dc.subjectDangling endsen
dc.subjectBase pairsen
dc.subjectPredictionen
dc.subjectSelectionen
dc.subjectSequencesen
dc.subjectEfficacyen
dc.titleComparison of approaches for rational siRNA design leading to a new efficient and transparent methoden
dc.typeArticle (peer-reviewed)en
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