Pertea Mihaela, Mount Stephen M, Salzberg Steven L
Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.
BMC Bioinformatics. 2007 May 21;8:159. doi: 10.1186/1471-2105-8-159.
Algorithmic approaches to splice site prediction have relied mainly on the consensus patterns found at the boundaries between protein coding and non-coding regions. However exonic splicing enhancers have been shown to enhance the utilization of nearby splice sites.
We have developed a new computational technique to identify significantly conserved motifs involved in splice site regulation. First, 84 putative exonic splicing enhancer hexamers are identified in Arabidopsis thaliana. Then a Gibbs sampling program called ELPH was used to locate conserved motifs represented by these hexamers in exonic regions near splice sites in confirmed genes. Oligomers containing 35 of these motifs have been shown experimentally to induce significant inclusion of A. thaliana exons. Second, integration of our regulatory motifs into two different splice site recognition programs significantly improved the ability of the software to correctly predict splice sites in a large database of confirmed genes. We have released GeneSplicerESE, the improved splice site recognition code, as open source software.
Our results show that the use of the ESE motifs consistently improves splice site prediction accuracy.
剪接位点预测的算法方法主要依赖于在蛋白质编码区和非编码区边界发现的共有模式。然而，外显子剪接增强子已被证明可增强附近剪接位点的使用。
我们开发了一种新的计算技术来识别参与剪接位点调控的显著保守基序。首先，在拟南芥中鉴定出84个假定的外显子剪接增强子六聚体。然后，使用一个名为ELPH的吉布斯采样程序在已确认基因的剪接位点附近的外显子区域中定位由这些六聚体代表的保守基序。实验表明，包含其中35个基序的寡聚体可显著诱导拟南芥外显子的包含。其次，将我们的调控基序整合到两个不同的剪接位点识别程序中，显著提高了该软件在一个已确认基因的大型数据库中正确预测剪接位点的能力。我们已将改进后的剪接位点识别代码GeneSplicerESE作为开源软件发布。
我们的结果表明，使用外显子剪接增强子基序可持续提高剪接位点预测的准确性。
