Non-EST based prediction of exon skipping and intron retention events using Pfam information.
Non-EST based prediction of exon skipping and intron retention events using Pfam information.
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DOI：
10.1093/nar/gki870
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发表时间：
2005
影响因子：
14.9
通讯作者：
Backofen R
中科院分区：
文献类型：
--
作者：
Hiller M;Huse K;Platzer M;Backofen R
大多数已知的选择性剪接事件都是通过比较表达序列标签（EST）和cDNA来检测的。然而，并不是所有的剪接事件在EST数据库中表示，因为EST有几个偏见。因此，需要非EST为基础的方法来扩展我们的观点的转录组。在这里，我们描述了一种新的方法从头预测的选择性剪接事件，是完全基于Pfam结构域的注释。此外，我们以全基因组的方式将这种方法应用于所有人类RefSeq转录本，并预测了总共321个外显子跳跃和内含子保留事件。我们表明，这种方法是非常可靠的，因为我们的预测78%（321个中的250个）被EST或cDNA证实。随后的Pfam结构域内的剪接事件的分析揭示了一个显着的偏好选择性外显子连接位于蛋白质表面，以避免二级结构元素。因此，Pfams内的剪接事件可能改变结构域的结构和功能，这使得它们对于详细的生物学研究非常感兴趣。由于Pfam结构域在许多其他物种中被注释，因此我们预测外显子跳跃和内含子保留事件的策略对于EST数量较少的物种可能很重要。
Most of the known alternative splice events have been detected by the comparison of expressed sequence tags (ESTs) and cDNAs. However, not all splice events are represented in EST databases since ESTs have several biases. Therefore, non-EST based approaches are needed to extend our view of a transcriptome. Here, we describe a novel method for the ab initio prediction of alternative splice events that is solely based on the annotation of Pfam domains. Furthermore, we applied this approach in a genome-wide manner to all human RefSeq transcripts and predicted a total of 321 exon skipping and intron retention events. We show that this method is very reliable as 78% (250 of 321) of our predictions are confirmed by ESTs or cDNAs. Subsequent analyses of splice events within Pfam domains revealed a significant preference of alternative exon junctions to be located at the protein surface and to avoid secondary structure elements. Thus, splice events within Pfams are probable to alter the structure and function of a domain which makes them highly interesting for detailed biological investigation. As Pfam domains are annotated in many other species, our strategy to predict exon skipping and intron retention events might be important for species with a lower number of ESTs.