Abstract
The design of small interfering RNA (siRNA) is a multi factorial problem that has gained the attention of many researchers in the area of therapeutic and functional genomics. MysiRNA score was previously introduced that improves the correlation of siRNA activity prediction considering state of the art algorithms. In this paper, a new program, MysiRNA-Designer, is described which integrates several factors in an automated work-flow considering mRNA transcripts variations, siRNA and mRNA target accessibility, and both near-perfect and partial off-target matches. It also features the MysiRNA score, a highly ranked correlated siRNA efficacy prediction score for ranking the designed siRNAs, in addition to top scoring models Biopredsi, DISR, Thermocomposition21 and i-Score, and integrates them in a unique siRNA score-filtration technique. This multi-score filtration layer filters siRNA that passes the 90% thresholds calculated from experimental dataset features. MysiRNA-Designer takes an accession, finds conserved regions among its transcript space, finds accessible regions within the mRNA, designs all possible siRNAs for these regions, filters them based on multi-scores thresholds, and then performs SNP and off-target filtration. These strict selection criteria were tested against human genes in which at least one active siRNA was designed from 95.7% of total genes. In addition, when tested against an experimental dataset, MysiRNA-Designer was found capable of rejecting 98% of the false positive siRNAs, showing superiority over three state of the art siRNA design programs. MysiRNA is a freely accessible (Microsoft Windows based) desktop application that can be used to design siRNA with a high accuracy and specificity. We believe that MysiRNA-Designer has the potential to play an important role in this area.
Highlights
SiRNAs are small double-stranded non-coding RNA molecules capable of utilizing the RNA interference gene regulatory mechanism
A multi-score filtration algorithm was implemented in MysiRNA-Designer that takes into account the intersection between ten small interfering RNA (siRNA) scoring tools
It was found that 95.65% of the mRNAs had at least one siRNA that met the selection criteria
Summary
SiRNAs are small double-stranded non-coding RNA molecules capable of utilizing the RNA interference gene regulatory mechanism As such, they are capable of down-regulating mRNA and causing targeted gene silencing. They are capable of down-regulating mRNA and causing targeted gene silencing This induced gene silencing is naturally utilized to target foreign genetic elements inside cells and has been utilized extensively to identify gene functions (functional genomics studies) or even (as an ultimate goal) treat certain genemediated diseases such as Cancer. For this reason, siRNAs have become a core interest of many biological research laboratories in the last decade. Several efforts have been made to rationalize siRNA design, starting with Tuschl principles [1], Reynolds [2], Amarzguioui [3], Takasaki [4], Katoh [5], Ui-Tei [6], and Hsieh [7] who developed some of the first-generation position dependant tools for siRNA design that had a relatively low correlation to actual siRNA activity [8].
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