A Novel Method for Assessing the Statistical Significance of RNA-RNA Interactions Between Two Long RNAs
A Novel Method for Assessing the Statistical Significance of RNA-RNA Interactions Between Two Long RNAs
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评估两个长 RNA 之间 RNA-RNA 相互作用统计意义的新方法
DOI：
10.1089/cmb.2017.0260
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发表时间：
2018
影响因子：
1.7
通讯作者：
Hamada Michiaki
中科院分区：
文献类型：
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作者：
Fukunaga Tsukasa;Hamada Michiaki
RNA-RNA相互作用是非编码RNA（ncRNA）区域发挥生物学功能的关键机制。RNA-RNA相互作用的计算预测是检测新的RNA-RNA相互作用的重要方法，因为它们的生物实验的全面检测仍然是相当困难的。已经开发了许多RNA-RNA相互作用预测工具，但它们往往会产生许多假阳性。因此，评估计算预测相互作用的统计显着性是一项重要任务。然而，没有方法来评估适用于两个长RNA序列之间相互作用的RNA-RNA相互作用的统计学显著性。我们开发了一种方法来计算两个长RNA序列之间的最小相互作用能的p值。所开发的方法依赖于这样一个事实，即当RNA中的重复序列被掩蔽时，长RNA之间的RNA-RNA相互作用的最小相互作用能遵循Gumbel分布。为了显示所开发的方法的有用性，我们将其应用于整个人类5′-非翻译区（UTR）和3′-UTR序列，以检测新的5′-UTR-3′-UTR相互作用。因此，我们确定了两个重要的5′-UTR-3′-UTR相互作用。具体而言，人类富含脯氨酸的小重复序列蛋白3显示出保守的5′-UTR-3′-UTR相互作用，其中一些核苷酸变异保留了灵长类动物之间的碱基配对。我们开发的方法使我们能够检测长RNA（如长ncRNA）之间统计学上显著的RNA-RNA相互作用。统计显著性估计有助于识别实验验证的相互作用，并提供新的见解ncRNA区域的功能。
RNA-RNA interactions are key mechanisms through which noncoding RNA (ncRNA) regions exert biological functions. Computational prediction of RNA-RNA interactions is an essential method for detecting novel RNA-RNA interactions because their comprehensive detection by biological experimentation is still quite difficult. Many RNA-RNA interaction prediction tools have been developed, but they tend to produce many false positives. Accordingly, assessment of the statistical significance of computationally predicted interactions is an important task. However, there is no method to evaluate the statistical significance of RNA-RNA interactions that is applicable to interactions between two long RNA sequences. We developed a method to calculate thep-value for the minimal interaction energy between two long RNA sequences. The developed method depends on the fact that minimum interaction energies of RNA-RNA interactions between long RNAs follow a Gumbel distribution when repeat sequences in RNAs are masked. To show the usefulness of the developed method, we applied it to whole human 5′-untranslated region (UTR) and 3′-UTR sequences to detect novel 5′-UTR-3′-UTR interactions. We thus identified two significant 5′-UTR-3′-UTR interactions. Specifically, the human small proline-rich repeat protein 3 shows conserved 5′-UTR-3′-UTR interactions with some nucleotide variations preserving base pairings among primates. Our developed method enables us to detect statistically significant RNA-RNA interactions between long RNAs such as long ncRNAs. Statistical significance estimates help in identification of interactions for experimental validation and provide novel insights into the function of ncRNA regions.