Inferring global levels of alternative splicing isoforms using a generative model of microarray data
Inferring global levels of alternative splicing isoforms using a generative model of microarray data
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DOI：
10.1093/bioinformatics/btk028
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发表时间：
2006-03-01
期刊：
影响因子：
5.8
通讯作者：
Frey, BJ
中科院分区：
文献类型：
--
作者：
Shai, O;Morris, QD;Frey, BJ
动机：选择性剪接（alternative splicing，AS）是后生动物基因表达中的一个重要步骤，基因的外显子以不同的组合方式进行剪接，产生多种成熟mRNA。AS的功能是丰富生物体的蛋白质组复杂性并调节基因表达。尽管其重要性，AS及其调控的机制还没有得到很好的理解，特别是在全球基因表达模式的背景下。我们在这里提出了一种算法，称为生成模型的替代剪接阵列平台（GenASAP），可以预测水平的AS为数千个外显子跳跃事件使用自定义微阵列生成的数据。GenASAP在无监督的概率模型中使用贝叶斯学习来准确预测来自微阵列数据的AS水平。GenASAP能够学习微阵列数据的杂交谱，同时对噪声过程和缺失或异常数据进行建模。GenASAP已成功地应用于全球发现和分析AS在哺乳动物细胞和tissues.Results：GenASAP被应用于从定制的微阵列获得的数据，该微阵列设计用于监测小鼠细胞和组织中的3126 AS事件。微阵列设计包括外显子体特异性探针和外显子剪接形成的连接序列。我们的研究结果表明，GenASAP提供了准确的预测超过三分之一的总事件，由独立的RT-PCR检测验证。http://www.psi.toronto.edu/GenASAP
Motivation: Alternative splicing (AS) is a frequent step in metozoan gene expression whereby the exons of genes are spliced in different combinations to generate multiple isoforms of mature mRNA. AS functions to enrich an organism's proteomic complexity and regulates gene expression. Despite its importance, the mechanisms underlying AS and its regulation are not well understood, especially in the context of global gene expression patterns. We present here an algorithm referred to as the Generative model for the Alternative Splicing Array Platform (GenASAP) that can predict the levels of AS for thousands of exon skipping events using data generated from custom microarrays. GenASAP uses Bayesian learning in an unsupervised probability model to accurately predict AS levels from the microarray data. GenASAP is capable of learning the hybridization profiles of microarray data, while modeling noise processes and missing or aberrant data. GenASAP has been successfully applied to the global discovery and analysis of AS in mammalian cells and tissues.Results: GenASAP was applied to data obtained from a custom microarray designed for the monitoring of 3126 AS events in mouse cells and tissues. The microarray design included probes specific for exon body and junction sequences formed by the splicing of exons. Our results show that GenASAP provides accurate predictions for over one-third of the total events, as verified by independent RT-PCR assays.Contact: ofer@psi.toronto.eduSupplementary information: http://www.psi.toronto.edu/GenASAP.