PubMed Health⌕ Search

Biomedical subjects

Shigeru Takasaki

Publications and source records attributed to Shigeru Takasaki.

3 recordsLinked to original sources

Selecting effective siRNA sequences based on the self-organizing map and statistical techniques.

Short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells but varies markedly in its gene-silencing efficacy. Although many design rules/guidelines for effective siRNAs based on various criteria have been reported recently, there are only a few consistencies among them. This makes it difficult to select effective siRNA sequences in mammalian genes. Here, we propose a new method for selecting effective siRNA target sequences on the basis of the self-organizing map (SOM) technique and statistical significance analyses for a large number of effective siRNAs. In the proposed method, the score is defined as a gene degradation measure. The effectiveness for the proposed method was confirmed by evaluating effective and ineffective siRNAs for recently reported genes (12 genes, 172 siRNA sequences) and comparing with other reported scoring methods. The size (value) of this score is closely correlated with the degree of gene degradation, and the score can easily be used for selecting high-potential siRNA candidates. The evaluation results indicate that the proposed method would be useful for many other genes. It will therefore be useful for selecting siRNA sequences in mammalian genes.

Animals↗

Selecting effective siRNA target sequences for mammalian genes.

Short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells but varies markedly in its gene-silencing efficacy in mammalian genes. The recently reported guidelines for selecting effective siRNA target sequences are not always useful for selecting highly effective siRNA sequences for many other mammalian genes because there are only a few consistencies among them. Hypothesizing that the positional nucleotide occurrence trends play an important role in effective gene-silencing, we examined 361 effective siRNA sequences from 227 different mammalian cDNAs in the literature and found got several nucleotide features different from the ones used in the previous guidelines. Here we first explain the problems concerning the previous guidelines from the qualitative and quantitative points of view. Then after clarifying the requirements for effective siRNA designs, we describe a new method based on a gene degradation measure defined by positional features of specific significant nucleotides. Testing the method on human cyclin B1 confirmed that it selected highly effective gene-silencing sequences and also indicated that it would be useful for other genes. It will therefore be useful for selecting new siRNA target sequences for mammalian genes.

Animals↗

An effective method for selecting siRNA target sequences in mammalian cells.

RNA interference is a gene-silencing phenomenon triggered by dsRNA (double-stranded RNA) and has been widely used for studying gene functions. The short interfering RNA (siRNA) responsible for RNA interference, however, varies markedly in its gene-silencing efficacy. Because this efficacy depends on the selected target sequences, we developed an effective selection method based on the gene degradation measure (priority score) defined by positional features of individual nucleotides. We tested this method experimentally by using it to select new siRNA target sequences in the homo sapiens cyclin B1 gene (CCNB1) and confirmed that it selected highly effective gene-silencing sequences. The proposed method will therefore be useful for selecting new siRNA target sequences in mammalian cells.

Animals↗