A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants

A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants
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DOI:
10.1186/1471-2105-8-180
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发表时间:
2007-06-04
期刊:
影响因子:
3
通讯作者:
Auboeuf, Didier
Auboeuf, Didier
中科院分区:
生物学4区
文献类型:
--
作者:
de la Grange, Pierre;Dutertre, Martin;Auboeuf, Didier

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背景:大多数人类基因通过不同的启动子、不同的聚腺苷酸化位点和不同的剪接位点产生不同外显子含量的转录本。通过开发大量的数据库,已经投入了大量的努力来描述已知的基因转录本。然而,由于转录组的多样性,需要建立交互式数据库,以提供有关每种剪接变体的潜在功能及其表达模式的信息。描述:在建立了人类和小鼠剪接变异体的数据库后,我们开发了工具(1)来预测这些转录本的蛋白质异构体的产生,考虑到开放阅读框架的存在和可能消除转录本和/或抑制其翻译的机制,即无义介导的mRNA衰变和microRNAs;(2)支持在多个水平上对转录物表达的调控研究,包括转录和剪接,特别是在组织特异性方面;(3)协助剪接变异体表达的实验分析。重要的是,从转录物代谢到功能蛋白结构域的所有特征分析都集成在一个高度交互,用户友好的网络界面中,允许快速准确地评估基因转录物的功能和调控特征。结论:除了鉴定人类和小鼠基因产生的转录本外,fast DB http://www.fast-db.com还为分析这些转录本的推测功能及其表达调控提供了工具。因此,fast DB通过为人类和小鼠基因组剪接变异的功能解释提供资源,在替代剪接数据库方面取得了进展。由于基因表达研究越来越多地应用于临床分析,我们的网络界面被设计得尽可能用户友好,并且易于被整个生物医学界检索和理解。
Background: Most human genes produce several transcripts with different exon contents by using alternative promoters, alternative polyadenylation sites and alternative splice sites. Much effort has been devoted to describing known gene transcripts through the development of numerous databases. Nevertheless, owing to the diversity of the transcriptome, there is a need for interactive databases that provide information about the potential function of each splicing variant, as well as its expression pattern.Description: After setting up a database in which human and mouse splicing variants were compiled, we developed tools (1) to predict the production of protein isoforms from these transcripts, taking account of the presence of open reading frames and mechanisms that could potentially eliminate transcripts and/or inhibit their translation, i.e. nonsense-mediated mRNA decay and microRNAs; (2) to support studies of the regulation of transcript expression at multiple levels, including transcription and splicing, particularly in terms of tissue specificity; and (3) to assist in experimental analysis of the expression of splicing variants. Importantly, analyses of all features from transcript metabolism to functional protein domains were integrated in a highly interactive, user-friendly web interface that allows the functional and regulatory features of gene transcripts to be assessed rapidly and accurately.Conclusion: In addition to identifying the transcripts produced by human and mouse genes, fast DB http://www.fast-db.com provides tools for analyzing the putative functions of these transcripts and the regulation of their expression. Therefore, fast DB has achieved an advance in alternative splicing databases by providing resources for the functional interpretation of splicing variants for the human and mouse genomes. Because gene expression studies are increasingly employed in clinical analyses, our web interface has been designed to be as user-friendly as possible and to be readily searchable and intelligible at a glance by the whole biomedical community.