Abstract folding space analysis based on helices
Abstract folding space analysis based on helices
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DOI：
10.1261/rna.033548.112
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发表时间：
2012-12-01
期刊：
影响因子：
4.5
通讯作者：
Voss, Bjoern
中科院分区：
文献类型：
--
作者：
Huang, Jiabin;Backofen, Rolf;Voss, Bjoern
RNA具有许多重要的功能，尤其是在通过ncRNA调节基因表达方面。识别其结构是了解其功能的重要要求。由于算法问题、参数不准确和生物特性，单独的结构预测通常不足以完成这项任务。在后者中，存在碱基修饰、导致折叠陷阱的共转录折叠和如核糖开关的情况下的构象转换。这些都需要对折叠空间进行更深入的分析。所有方法都必须科普的主要缺点是折叠空间的指数增长。因此，方法通常受限于它们可以分析的序列长度，或者它们利用了分析、采样或抽象。我们的方法采用了抽象策略，并弥补了现有方法的一些问题。我们引入了一个位置特定的抽象的基础上螺旋，我们的术语螺旋指数形状，或hishanges为短。利用动态编程框架，我们已经实现了这个抽象的程序RNAHeliCes。此外，我们开发了两种基于hishape的方法，一种用于能量势垒估计，称为HiPath，另一种用于抽象结构比较，称为HiTed。我们证明了上级性能的HiPath相比，其他现有的方法和竞争力的准确性HiTed。RNAHeliCes以及HiPath和HiTed可在http://www.cyanolab.de/software/RNAHeliCes.htm下载。
RNA has many pivotal functions especially in the regulation of gene expression by ncRNAs. Identification of their structure is an important requirement for understanding their function. Structure prediction alone is often insufficient for this task, due to algorithmic problems, parameter inaccuracies, and biological peculiarities. Among the latter, there are base modifications, cotranscriptional folding leading to folding traps, and conformational switching as in the case of riboswitches. All these require more in-depth analysis of the folding space. The major drawback, which all methods have to cope with, is the exponential growth of the folding space. Therefore, methods are often limited in the sequence length they can analyze, or they make use of heuristics, sampling, or abstraction. Our approach adopts the abstraction strategy and remedies some problems of existing methods. We introduce a position-specific abstraction based on helices that we term helix index shapes, or hishapes for short. Utilizing a dynamic programming framework, we have implemented this abstraction in the program RNAHeliCes. Furthermore, we developed two hishape-based methods, one for energy barrier estimation, called HiPath, and one for abstract structure comparison, termed HiTed. We demonstrate the superior performance of HiPath compared to other existing methods and the competitive accuracy of HiTed. RNAHeliCes, together with HiPath and HiTed, are available for download at http://www.cyanolab.de/software/RNAHeliCes.htm.