Stable stem enabled Shannon entropies distinguish non-coding RNAs from random backgrounds.

Stable stem enabled Shannon entropies distinguish non-coding RNAs from random backgrounds.
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DOI:
10.1186/1471-2105-13-s5-s1
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发表时间:
2012-04-12
期刊:
影响因子:
3
通讯作者:
Cai L
Cai L
中科院分区:
生物学4区
文献类型:
--
作者:
Wang Y;Manzour A;Shareghi P;Shaw TI;Li YW;Malmberg RL;Cai L

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基因组序列中 RNA 的计算识别需要识别 RNA 序列的信号。香农碱基配对熵是结构非编码 RNA (ncRNA) 检测中 RNA 二级结构折叠确定性的指标。在二级结构的玻尔兹曼系综下,碱基对的概率是根据其在所有替代平衡结构中的频率来估计的。然而,这样的熵尚未提供区分 ncRNA 和随机序列所需的性能。开发新方法来提高熵测量性能可能会导致基于结构检测的更有效的 ncRNA 基因发现。本文表明,使用受约束的二级结构集合可以显着提高碱基配对熵的测量性能,其中假设仅规范碱基对出现在折叠中的能量稳定的茎中。这种限制实际上减少了二级结构的空间,并且可能降低不利于天然折叠的碱基对的概率。事实上,与改组序列相比,使用此约束模型计算的碱基配对熵表明 ncRNA 之间的 Z 分数差距大大缩小,并且所有 13 个测试的 ncRNA 组的 Z 分数急剧增加。这些结果表明通过研究 ncRNA 二级结构整体来开发有效的基于结构的 ncRNA 基因寻找方法的可行性。
The computational identification of RNAs in genomic sequences requires the identification of signals of RNA sequences. Shannon base pairing entropy is an indicator for RNA secondary structure fold certainty in detection of structural, non-coding RNAs (ncRNAs). Under the Boltzmann ensemble of secondary structures, the probability of a base pair is estimated from its frequency across all the alternative equilibrium structures. However, such an entropy has yet to deliver the desired performance for distinguishing ncRNAs from random sequences. Developing novel methods to improve the entropy measure performance may result in more effective ncRNA gene finding based on structure detection. This paper shows that the measuring performance of base pairing entropy can be significantly improved with a constrained secondary structure ensemble in which only canonical base pairs are assumed to occur in energetically stable stems in a fold. This constraint actually reduces the space of the secondary structure and may lower the probabilities of base pairs unfavorable to the native fold. Indeed, base pairing entropies computed with this constrained model demonstrate substantially narrowed gaps of Z-scores between ncRNAs, as well as drastic increases in the Z-score for all 13 tested ncRNA sets, compared to shuffled sequences. These results suggest the viability of developing effective structure-based ncRNA gene finding methods by investigating secondary structure ensembles of ncRNAs.