Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities.
Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities.
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DOI：
10.1093/nar/gkm699
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发表时间：
2007
影响因子：
14.9
通讯作者：
Ohno, Kinji
中科院分区：
文献类型：
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作者：
Ichihara, Masatoshi;Murakumo, Yoshiki;Masuda, Akio;Matsuura, Toru;Asai, Naoya;Jijiwa, Mayumi;Ishida, Maki;Shinmi, Jun;Yatsuya, Hiroshi;Qiao, Shanlou;Takahashi, Masahide;Ohno, Kinji
我们开发了一个简单的算法，i-Score (inhibition - score)，通过对2431个sirna应用线性回归模型来预测活性sirna。我们的算法完全由每个位置的核苷酸（nt）偏好组成，没有考虑其他参数。使用419个sirna验证数据，我们发现i-Score的预测精度与s-Biopredsi、thermocomtion21和DSIR的预测精度相当，后者采用神经网络模型或在线性回归模型中使用更多参数。Reynolds和Katoh也能有效地预测活性sirna，但预测活性sirna的数量不到i-Score的八分之一。我们还发现，排除总堆叠能（ΔG）小于−34.6 kcal/mol的耐热sirna，可以提高i-Score、s-Biopredsi、thermocomtion21和DSIR的预测精度。我们还开发了一个通用的目标载体pSELL，用它我们可以在正义或反义方向上检测任何序列的siRNA活性。我们使用pSELL检测了HEK293细胞中的86种sirna，并验证了i-Score和整个ΔG值在sirna设计中的适用性。
We developed a simple algorithm, i-Score (inhibitory-Score), to predict active siRNAs by applying a linear regression model to 2431 siRNAs. Our algorithm is exclusively comprised of nucleotide (nt) preferences at each position, and no other parameters are taken into account. Using a validation dataset comprised of 419 siRNAs, we found that the prediction accuracy of i-Score is as good as those of s-Biopredsi, ThermoComposition21 and DSIR, which employ a neural network model or more parameters in a linear regression model. Reynolds and Katoh also predict active siRNAs efficiently, but the numbers of siRNAs predicted to be active are less than one-eighth of that of i-Score. We additionally found that exclusion of thermostable siRNAs, whose whole stacking energy (ΔG) is less than −34.6 kcal/mol, improves the prediction accuracy in i-Score, s-Biopredsi, ThermoComposition21 and DSIR. We also developed a universal target vector, pSELL, with which we can assay an siRNA activity of any sequence in either the sense or antisense direction. We assayed 86 siRNAs in HEK293 cells using pSELL, and validated applicability of i-Score and the whole ΔG value in designing siRNAs.