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Designing of Highly Effective Complementary and Mismatch siRNAs for Silencing a Gene

In past, numerous methods have been developed for predicting efficacy of short interfering RNA (siRNA). However these methods have been developed for predicting efficacy of fully complementary siRNA against a gene. Best of author's knowledge no method has been developed for predicting efficacy...

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Detalles Bibliográficos
Autores principales: Ahmed, Firoz, Raghava, Gajendra P. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154470/
https://www.ncbi.nlm.nih.gov/pubmed/21853133
http://dx.doi.org/10.1371/journal.pone.0023443
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author Ahmed, Firoz
Raghava, Gajendra P. S.
author_facet Ahmed, Firoz
Raghava, Gajendra P. S.
author_sort Ahmed, Firoz
collection PubMed
description In past, numerous methods have been developed for predicting efficacy of short interfering RNA (siRNA). However these methods have been developed for predicting efficacy of fully complementary siRNA against a gene. Best of author's knowledge no method has been developed for predicting efficacy of mismatch siRNA against a gene. In this study, a systematic attempt has been made to identify highly effective complementary as well as mismatch siRNAs for silencing a gene. Support vector machine (SVM) based models have been developed for predicting efficacy of siRNAs using composition, binary and hybrid pattern siRNAs. We achieved maximum correlation 0.67 between predicted and actual efficacy of siRNAs using hybrid model. All models were trained and tested on a dataset of 2182 siRNAs and performance was evaluated using five-fold cross validation techniques. The performance of our method desiRm is comparable to other well-known methods. In this study, first time attempt has been made to design mutant siRNAs (mismatch siRNAs). In this approach we mutated a given siRNA on all possible sites/positions with all possible nucleotides. Efficacy of each mutated siRNA is predicted using our method desiRm. It is well known from literature that mismatches between siRNA and target affects the silencing efficacy. Thus we have incorporated the rules derived from base mismatches experimental data to find out over all efficacy of mutated or mismatch siRNAs. Finally we developed a webserver, desiRm (http://www.imtech.res.in/raghava/desirm/) for designing highly effective siRNA for silencing a gene. This tool will be helpful to design siRNA to degrade disease isoform of heterozygous single nucleotide polymorphism gene without depleting the wild type protein.
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spelling pubmed-31544702011-08-18 Designing of Highly Effective Complementary and Mismatch siRNAs for Silencing a Gene Ahmed, Firoz Raghava, Gajendra P. S. PLoS One Research Article In past, numerous methods have been developed for predicting efficacy of short interfering RNA (siRNA). However these methods have been developed for predicting efficacy of fully complementary siRNA against a gene. Best of author's knowledge no method has been developed for predicting efficacy of mismatch siRNA against a gene. In this study, a systematic attempt has been made to identify highly effective complementary as well as mismatch siRNAs for silencing a gene. Support vector machine (SVM) based models have been developed for predicting efficacy of siRNAs using composition, binary and hybrid pattern siRNAs. We achieved maximum correlation 0.67 between predicted and actual efficacy of siRNAs using hybrid model. All models were trained and tested on a dataset of 2182 siRNAs and performance was evaluated using five-fold cross validation techniques. The performance of our method desiRm is comparable to other well-known methods. In this study, first time attempt has been made to design mutant siRNAs (mismatch siRNAs). In this approach we mutated a given siRNA on all possible sites/positions with all possible nucleotides. Efficacy of each mutated siRNA is predicted using our method desiRm. It is well known from literature that mismatches between siRNA and target affects the silencing efficacy. Thus we have incorporated the rules derived from base mismatches experimental data to find out over all efficacy of mutated or mismatch siRNAs. Finally we developed a webserver, desiRm (http://www.imtech.res.in/raghava/desirm/) for designing highly effective siRNA for silencing a gene. This tool will be helpful to design siRNA to degrade disease isoform of heterozygous single nucleotide polymorphism gene without depleting the wild type protein. Public Library of Science 2011-08-10 /pmc/articles/PMC3154470/ /pubmed/21853133 http://dx.doi.org/10.1371/journal.pone.0023443 Text en Ahmed, Raghava. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ahmed, Firoz
Raghava, Gajendra P. S.
Designing of Highly Effective Complementary and Mismatch siRNAs for Silencing a Gene
title Designing of Highly Effective Complementary and Mismatch siRNAs for Silencing a Gene
title_full Designing of Highly Effective Complementary and Mismatch siRNAs for Silencing a Gene
title_fullStr Designing of Highly Effective Complementary and Mismatch siRNAs for Silencing a Gene
title_full_unstemmed Designing of Highly Effective Complementary and Mismatch siRNAs for Silencing a Gene
title_short Designing of Highly Effective Complementary and Mismatch siRNAs for Silencing a Gene
title_sort designing of highly effective complementary and mismatch sirnas for silencing a gene
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154470/
https://www.ncbi.nlm.nih.gov/pubmed/21853133
http://dx.doi.org/10.1371/journal.pone.0023443
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