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Comparison of approaches for rational siRNA design leading to a new efficient and transparent method
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. Acc...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885645/ https://www.ncbi.nlm.nih.gov/pubmed/17426130 http://dx.doi.org/10.1093/nar/gkm088 |
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author | Matveeva, Olga Nechipurenko, Yury Rossi, Leo Moore, Barry Sætrom, Pål Ogurtsov, Aleksey Y. Atkins, John F. Shabalina, Svetlana A. |
author_facet | Matveeva, Olga Nechipurenko, Yury Rossi, Leo Moore, Barry Sætrom, Pål Ogurtsov, Aleksey Y. Atkins, John F. Shabalina, Svetlana A. |
author_sort | Matveeva, Olga |
collection | PubMed |
description | 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’. |
format | Text |
id | pubmed-1885645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-18856452007-06-07 Comparison of approaches for rational siRNA design leading to a new efficient and transparent method Matveeva, Olga Nechipurenko, Yury Rossi, Leo Moore, Barry Sætrom, Pål Ogurtsov, Aleksey Y. Atkins, John F. Shabalina, Svetlana A. Nucleic Acids Res Methods Online 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’. Oxford University Press 2007-04 2007-04-10 /pmc/articles/PMC1885645/ /pubmed/17426130 http://dx.doi.org/10.1093/nar/gkm088 Text en © 2007 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Methods Online Matveeva, Olga Nechipurenko, Yury Rossi, Leo Moore, Barry Sætrom, Pål Ogurtsov, Aleksey Y. Atkins, John F. Shabalina, Svetlana A. Comparison of approaches for rational siRNA design leading to a new efficient and transparent method |
title | Comparison of approaches for rational siRNA design leading to a new efficient and transparent method |
title_full | Comparison of approaches for rational siRNA design leading to a new efficient and transparent method |
title_fullStr | Comparison of approaches for rational siRNA design leading to a new efficient and transparent method |
title_full_unstemmed | Comparison of approaches for rational siRNA design leading to a new efficient and transparent method |
title_short | Comparison of approaches for rational siRNA design leading to a new efficient and transparent method |
title_sort | comparison of approaches for rational sirna design leading to a new efficient and transparent method |
topic | Methods Online |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885645/ https://www.ncbi.nlm.nih.gov/pubmed/17426130 http://dx.doi.org/10.1093/nar/gkm088 |
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