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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Autores principales:	Firoz Ahmed, Gajendra P S Raghava
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/28371b98860f41eba7ecbe0e7f1d831e
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spelling	oai:doaj.org-article:28371b98860f41eba7ecbe0e7f1d831e2021-11-18T06:48:16ZDesigning of highly effective complementary and mismatch siRNAs for silencing a gene.1932-620310.1371/journal.pone.0023443https://doaj.org/article/28371b98860f41eba7ecbe0e7f1d831e2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21853133/?tool=EBIhttps://doaj.org/toc/1932-6203In 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.Firoz AhmedGajendra P S RaghavaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23443 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Firoz Ahmed Gajendra P S Raghava Designing of highly effective complementary and mismatch siRNAs for silencing a gene.
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.
format	article
author	Firoz Ahmed Gajendra P S Raghava
author_facet	Firoz Ahmed Gajendra P S Raghava
author_sort	Firoz Ahmed
title	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_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_sort	designing of highly effective complementary and mismatch sirnas for silencing a gene.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/28371b98860f41eba7ecbe0e7f1d831e
work_keys_str_mv	AT firozahmed designingofhighlyeffectivecomplementaryandmismatchsirnasforsilencingagene AT gajendrapsraghava designingofhighlyeffectivecomplementaryandmismatchsirnasforsilencingagene
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Designing of highly effective complementary and mismatch siRNAs for silencing a gene.

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