Foissac Sylvain, Schiex Thomas
Unité de Biométrie et Intelligence Artificielle, INRA, 31326 Castanet Tolosan, France.
BMC Bioinformatics. 2005 Feb 10;6:25. doi: 10.1186/1471-2105-6-25.
Alternative splicing (AS) is now considered as a major actor in transcriptome/proteome diversity and it cannot be neglected in the annotation process of a new genome. Despite considerable progresses in term of accuracy in computational gene prediction, the ability to reliably predict AS variants when there is local experimental evidence of it remains an open challenge for gene finders.
We have used a new integrative approach that allows to incorporate AS detection into ab initio gene prediction. This method relies on the analysis of genomically aligned transcript sequences (ESTs and/or cDNAs), and has been implemented in the dynamic programming algorithm of the graph-based gene finder EuGENE. Given a genomic sequence and a set of aligned transcripts, this new version identifies the set of transcripts carrying evidence of alternative splicing events, and provides, in addition to the classical optimal gene prediction, alternative optimal predictions (among those which are consistent with the AS events detected). This allows for multiple annotations of a single gene in a way such that each predicted variant is supported by a transcript evidence (but not necessarily with a full-length coverage).
This automatic combination of experimental data analysis and ab initio gene finding offers an ideal integration of alternatively spliced gene prediction inside a single annotation pipeline.
可变剪接(AS)如今被视为转录组/蛋白质组多样性的一个主要因素,在新基因组的注释过程中不容忽视。尽管在计算基因预测的准确性方面取得了相当大的进展,但当存在局部实验证据时,可靠预测AS变体的能力对基因发现工具来说仍是一个悬而未决的挑战。
我们采用了一种新的综合方法,能够将AS检测纳入从头基因预测中。该方法依赖于对基因组比对的转录序列(EST和/或cDNA)进行分析,并已在基于图的基因发现工具EuGENE的动态规划算法中实现。给定一个基因组序列和一组比对的转录本,这个新版本会识别出携带可变剪接事件证据的转录本集合,并且除了经典的最优基因预测外,还会提供替代的最优预测(在与检测到的AS事件一致的那些预测中)。这允许以一种每个预测变体都有转录本证据支持(但不一定是全长覆盖)的方式对单个基因进行多种注释。
这种实验数据分析与从头基因发现的自动结合,在单个注释流程中为可变剪接基因预测提供了理想的整合。