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Feature selection for siRNA efficacy prediction using natural computation

机译:使用自然计算的siRNA功效预测的特征选择

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RNAi is a naturally occurring, highly conserved phenomenon of RNA mediated gene silencing among the multicellular organisms. Currently, RNAi has been successfully applied in functional genomics, therapeutics and new drug target identification in mammals and other eukaryotes. The uniqueness lies in sequence specific gene knock down which made RNAi an indispensible technology. In the mechanism of RNAi, small 21-25 bp long, double stranded endogenously or exogenously generated RNA molecule via DICER; a RNAase III enzyme, resulting in the formation of multi-domain RISC structure. The slicer activity of RISC cleaves the complementary mRNA and blocks the transcription process, consequently the gene function. Many siRNA design tools have been developed following the general guidelines like rational design criteria with their uniquely defined features. These guidelines are based upon sequence to thermodynamic features of siRNA which plays crucial role in the effective designing of siRNA. But no tool provides the accurate gene specific siRNA sequences with absolute efficacy. Furthermore, selection of suitable siRNA from the bunch of predicted sequences is the most intriguing challenge even now. So identification of features for effective siRNA design is the very smoldering issue to be solved in the present scenario since feature selection is computationally a NP hard problem. In this paper, we have presented an ant colony optimization based meta-heuristic methodology to indentify the features of siRNA up to the considerable amount of accuracy and further the results are analyzed using linear regression and ANCOVA methods. It has been observed that sequence based features are comparatively significant than thermodynamic features. Further the analysis reveals that both sequence and thermodynamic features are simultaneously important in the effective designing of siRNA.
机译:RNAi是一种天然存在的,高度保守的RNA介导的基因在多细胞生物中沉默的现象。目前,RNAI已成功应用于哺乳动物和其他真核生物的功能基因组学,治疗和新药物靶标鉴定。唯一性在于序列特异性基因敲击,使RNAi成为不可或缺的技术。在RNAi的机理中,小21-25bp长,双链内源性或外源通过加床产生的RNA分子; RNA酶III酶,导致多域RISC结构的形成。 RISC的切片器活性切割互补mRNA并阻断转录过程,因此基因功能。许多SiRNA设计工具已经在概括的设计标准之类的一般指导方面开发,具有唯一定义的功能。这些指南基于siRNA的热力学特征序列,其在有效设计siRNA中起着至关重要的作用。但没有工具提供绝对功效的准确基因特异性siRNA序列。此外,从一堆预测序列中选择合适的siRNA是即使是现在最有趣的挑战。因此,鉴定有效si​​RNA设计的特征是在本场景中解决的非常闷烧的问题,因为特征选择是计算的NP难题。在本文中,我们介绍了基于蚁群优化的元启发式方法,以识别siRNA的特征,其高达相当数量的精度,并且使用线性回归和ANCOVA方法分析结果。已经观察到基于序列的特征比热力学特征相对显着。此外,分析表明,序列和热动力学特征在SiRNA的有效设计中同时重要。

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