Abstract
BackgroundAlthough short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells, its gene silencing efficacy varies markedly and there are only a few consistencies among the recently reported design rules/guidelines for selecting siRNA sequences effective for mammalian genes. Another shortcoming of the previously reported methods is that they cannot estimate the probability that a candidate sequence will silence the target gene.ResultsWe propose two prediction methods for selecting effective siRNA target sequences from many possible candidate sequences, one based on the supervised learning of a radial basis function (RBF) network and other based on decision tree learning. They are quite different from the previous score-based siRNA design techniques and can predict the probability that a candidate siRNA sequence will be effective. The proposed methods were evaluated by applying them to recently reported effective and ineffective siRNA sequences for various genes (15 genes, 196 siRNA sequences). We also propose the combined prediction method of the RBF network and decision tree learning. As the average prediction probabilities of gene silencing for the effective and ineffective siRNA sequences of the reported genes by the proposed three methods were respectively 65% and 32%, 56.6% and 38.1%, and 68.5% and 28.1%, the methods imply high estimation accuracy for selecting candidate siRNA sequences.ConclusionNew prediction methods were presented for selecting effective siRNA sequences. As the proposed methods indicated high estimation accuracy for selecting candidate siRNA sequences, they would be useful for many other genes.
Highlights
Short interfering RNA has been widely used for studying gene functions in mammalian cells, its gene silencing efficacy varies markedly and there are only a few consistencies among the recently reported design rules/guidelines for selecting short interfering RNA (siRNA) sequences effective for mammalian genes
We propose two prediction methods for selecting effective siRNA sequences from many possible candidate sequences, one based on the supervised learning of radial basis function (RBF) and other based on the learning of decision tree
There is in RNA interference (RNAi) a risk of off-target regulation: a possibility that the siRNA will silence other genes whose sequences are similar to that of the target gene
Summary
Short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells, its gene silencing efficacy varies markedly and there are only a few consistencies among the recently reported design rules/guidelines for selecting siRNA sequences effective for mammalian genes. Another shortcoming of the previously reported methods is that they cannot estimate the probability that a candidate sequence will silence the target gene. The short interfering RNA (siRNA) responsible for RNA interference varies markedly in its gene silencing efficacy in mammalian genes, where the gene silencing effectiveness depends very much on the target sequence positions (sites) selected from the target gene [7,8]. We need useful criteria for gene silencing efficacy when we are designing siRNA sequences [9,10]
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