Prediction of alternatively skipped exons and splicing enhancers from exon junction arrays.
Prediction of alternatively skipped exons and splicing enhancers from exon junction arrays.
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DOI：
10.1186/1471-2164-9-551
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发表时间：
2008-11-20
期刊：
影响因子：
4.4
通讯作者：
Yeh, Ru-Fang
中科院分区：
文献类型：
--
作者：
Kechris, Katerina;Yang, Yee Hwa;Yeh, Ru-Fang
mRNA 前体转录物中外显子的选择性剪接是促进人类蛋白质多样性的重要机制。用于检测选择性剪接的阵列可使用几种不同的探针设计，包括基于外显子连接的探针设计。在这项工作中，我们引入了一种新方法来预测外显子连接阵列中交替跳过的外显子。将基于我们方法的预测与对照进行比较，并分析它们的序列以识别对于调节选择性剪接重要的基序。我们对几种替代方法的比较表明，基于相邻连接的外显子跳跃评分可以最好地区分阳性对照和阴性对照。我们预测的外显子的序列分析证实了已知剪接调控序列的存在。此外，我们还根据胎儿与成人组织的比较得出了一组与发育相关的选择性剪接基因，并发现我们的预测与其功能注释一致。应用从头开始基序查找算法来识别可能与发育过程中的剪接相关的几个基序。这项工作描述了一种分析外显子连接阵列的新方法，鉴定了选择性剪接和组成型剪接特异的序列基序，并提出了几种已知剪接因子及其基序在发育调节中的作用。
Alternative splicing of exons in a pre-mRNA transcript is an important mechanism which contributes to protein diversity in human. Arrays for detecting alternative splicing are available using several different probe designs, including those based on exon-junctions. In this work, we introduce a new method for predicting alternatively skipped exons from exon-junction arrays. Predictions based on our method are compared against controls and their sequences are analyzed to identify motifs important for regulating alternative splicing. Our comparison of several alternative methods shows that an exon-skipping score based on neighboring junctions best discriminates between positive and negative controls. Sequence analysis of our predicted exons confirms the presence of known splicing regulatory sequences. In addition, we also derive a set of development-related alternatively spliced genes based on fetal versus adult tissue comparisons and find that our predictions are consistent with their functional annotations. Ab initio motif finding algorithms are applied to identify several motifs that may be relevant for splicing during development. This work describes a new method for analyzing exon-junction arrays, identifies sequence motifs that are specific for alternative and constitutive splicing and suggests a role for several known splicing factors and their motifs in developmental regulation.
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