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Sunday, August 14, 2011

Fwd: [WebBio] Designing Complementary and Mismatch siRNAs for Silencing a Gene



---------- Forwarded message ----------
From: G P S Raghava <raghavagps@gmail.com>
Date: Thu, Aug 11, 2011 at 6:26 AM
Subject: [WebBio] Designing Complementary and Mismatch siRNAs for Silencing a Gene
To: "webbio: Web Servers for Biologists" <webbio@googlegroups.com>


We are please to announce a new server DESIRM from group which is
recently published in PLOS ONE
See http://dx.plos.org/10.1371/journal.pone.0023443 or
http://www.imtech.res.in/raghava/desirm/ .

Raghava


Abstract of paper

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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