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Identification of sequence–structure RNA binding motifs for SELEX-derived aptamers

机译:识别SELEX衍生的适体的序列结构RNA结合基序

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摘要

>Motivation: Systematic Evolution of Ligands by EXponential Enrichment (SELEX) represents a state-of-the-art technology to isolate single-stranded (ribo)nucleic acid fragments, named aptamers, which bind to a molecule (or molecules) of interest via specific structural regions induced by their sequence-dependent fold. This powerful method has applications in designing protein inhibitors, molecular detection systems, therapeutic drugs and antibody replacement among others. However, full understanding and consequently optimal utilization of the process has lagged behind its wide application due to the lack of dedicated computational approaches. At the same time, the combination of SELEX with novel sequencing technologies is beginning to provide the data that will allow the examination of a variety of properties of the selection process.>Results: To close this gap we developed, Aptamotif, a computational method for the identification of sequence–structure motifs in SELEX-derived aptamers. To increase the chances of identifying functional motifs, Aptamotif uses an ensemble-based approach. We validated the method using two published aptamer datasets containing experimentally determined motifs of increasing complexity. We were able to recreate the author's findings to a high degree, thus proving the capability of our approach to identify binding motifs in SELEX data. Additionally, using our new experimental dataset, we illustrate the application of Aptamotif to elucidate several properties of the selection process.>Contact: ,
机译:>动机::通过指数富集(SELEX)进行配体的系统进化代表了一种最新技术,该技术可分离与分子结合的单链(核糖)核酸片段,称为适体。或特定分子)通过其序列依赖性折叠诱导的特定结构区域。这种功能强大的方法可用于设计蛋白质抑制剂,分子检测系统,治疗药物和抗体替代等。然而,由于缺乏专用的计算方法,对该过程的充分理解以及因此的最佳利用已落后于其广泛的应用。同时,SELEX与新颖的测序技术的结合开始提供可用于检查选择过程各种属性的数据。>结果:为了弥补这一空白,我们开发了Aptamotif,一种识别SELEX衍生的适体中序列结构基序的计算方法。为了增加识别功能性图案的机会,Aptamotif使用基于整体的方法。我们使用两个已公开的适体数据集验证了该方法,所述适体数据集包含实验确定的复杂性不断提高的图案。我们能够在很大程度上重现作者的发现,从而证明了我们的方法能够识别SELEX数据中的结合基序。此外,使用新的实验数据集,我们说明了Aptamotif在阐明选择过程的几个属性方面的应用。>联系人:

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