Fast and reliable prediction of noncoding RNAs
Fast and reliable prediction of noncoding RNAs
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DOI：
10.1073/pnas.0409169102
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发表时间：
2005-02-15
影响因子：
11.1
通讯作者：
Stadler, PF
中科院分区：
文献类型：
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作者：
Washietl, S;Hofacker, IL;Stadler, PF
我们报告了一种检测功能性 RNA 的有效方法。该方法结合了比较序列分析和结构预测，已经对少量比对序列产生了优异的结果，适用于大规模基因组筛选。它由两个基本组成部分组成：(i) 基于计算共有二级结构的 RNA 二级结构保守性测量，以及 (h) 热力学稳定性测量，本着 z 分数的精神，根据序列长度和碱基组成进行归一化，但可以在不从改组序列中采样的情况下进行计算。功能性 RNA 二级结构可以通过多重序列比对进行鉴定，具有高灵敏度和高特异性。我们证明这种方法不仅比以前的方法更准确，而且速度也快得多。该方法在 RNAZ 程序中实现，该程序可以从 www.tbi.univie.ac.at/similar towash/RNAz 下载。我们在比较调控基因组数据库中筛选了长度n大于或等于50的所有比对，该数据库编译了来自人类、小鼠、大鼠、河豚和斑马鱼的直系同源基因上游区域的保守非编码元件。我们恢复了所有已知的非编码 RNA 和具有高度重要性的顺式作用元件，并发现了许多其他保守 RNA 二级结构的令人信服的证据，而这些二级结构迄今为止尚未被描述。
We report an efficient method for detecting functional RNAs. The approach, which combines comparative sequence analysis and structure prediction, already has yielded excellent results for a small number of aligned sequences and is suitable for large-scale genomic screens. It consists of two basic components: (i) a measure for RNA secondary structure conservation based on computing a consensus secondary structure, and (h) a measure for thermodynamic stability, which, in the spirit of a z score, is normalized with respect to both sequence length and base composition but can be calculated without sampling from shuffled sequences. Functional RNA secondary structures can be identified in multiple sequence alignments with high sensitivity and high specificity. We demonstrate that this approach is not only much more accurate than previous methods but also significantly faster. The method is implemented in the program RNAZ, which can be downloaded from www.tbi.univie.ac.at/similar towash/RNAz. We screened all alignments of length n greater than or equal to 50 in the Comparative Regulatory Genomics database, which compiles conserved noncoding elements in upstream regions of orthologous genes from human, mouse, rat, Fugu, and zebrafish. We recovered all of the known noncoding RNAs and cis-acting elements with high significance and found compelling evidence for many other conserved RNA secondary structures not described so far to our knowledge.