Institute of Bioinformatics and Systems Biology (MIPS), Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Bioinformatics. 2011 May 15;27(10):1346-50. doi: 10.1093/bioinformatics/btr149. Epub 2011 Mar 26.
Pairing between the target sequence and the 6-8 nt long seed sequence of the miRNA presents the most important feature for miRNA target site prediction. Novel high-throughput technologies such as Argonaute HITS-CLIP afford meanwhile a detailed study of miRNA:mRNA duplices. These interaction maps enable a first discrimination between functional and non-functional target sites in a bulky fashion. Prediction algorithms apply different seed paradigms to identify miRNA target sites. Therefore, a quantitative assessment of miRNA target site prediction is of major interest.
We identified a set of canonical seed types based on a transcriptome wide analysis of experimentally verified functional target sites. We confirmed the specificity of long seeds but we found that the majority of functional target sites are formed by less specific seeds of only 6 nt indicating a crucial role of this type. A substantial fraction of genuine target sites arenon-conserved. Moreover, the majority of functional sites remain uncovered by common prediction methods.
靶序列与 miRNA 中 6-8 个 nt 长的种子序列的配对是 miRNA 靶位点预测的最重要特征。Argonaute HITS-CLIP 等新型高通量技术同时提供了 miRNA:mRNA 双链的详细研究。这些相互作用图谱能够大规模地区分功能和非功能靶位点。预测算法应用不同的种子范式来识别 miRNA 靶位点。因此,对 miRNA 靶位点预测进行定量评估是非常重要的。
我们基于对实验验证的功能靶位点的转录组广泛分析,确定了一组典型的种子类型。我们证实了长种子的特异性,但我们发现大多数功能靶位点是由只有 6 个 nt 的不太特异的种子形成的,这表明这种类型的种子起着关键作用。大量真正的靶位点是非保守的。此外,大多数功能位点仍然没有被常见的预测方法所覆盖。