Suppr超能文献

利用基因芯片人类外显子1.0 ST阵列进行全基因组生物标志物剪接变异发现的统计框架。

A statistical framework for genome-wide discovery of biomarker splice variations with GeneChip Human Exon 1.0 ST Arrays.

作者信息

Yoshida Ryo, Numata Kazuyuki, Imoto Seiya, Nagasaki Masao, Doi Atsushi, Ueno Kazuko, Miyano Satoru

机构信息

Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639 Tokyo, Japan.

出版信息

Genome Inform. 2006;17(1):88-99.

Abstract

Alternative splicing is an important regulatory mechanism that generates multiple mRNA transcripts which are transcribed into functionally diverse proteins. According to the current studies, aberrant transcripts due to splicing mutations are known to cause for 15% of genetic diseases. Therefore understanding regulatory mechanism of alternative splicing is essential for identifying potential biomarkers for several types of human diseases. Most recently, advent of GeneChip Human Exon 1.0 ST Array enables us to measure genome-wide expression profiles of over one million exons. With this new microarray platform, analysis of functional gene expressions could be extended to detect not only differentially expressed genes, but also a set of specific-splicing events that are differentially observed between one or more experimental conditions, e.g. tumor or normal control cells. In this study, we address the statistical problems to identify differentially observed splicing variations from exon expression profiles. The proposed method is organized according to the following process: (1) Data preprocessing for removing systematic biases from the probe intensities. (2) Whole transcript analysis with the analysis of variance (ANOVA) to identify a set of loci that cause the alternative splicing-related to a certain disease. We test the proposed statistical approach on exon expression profiles of colorectal carcinoma. The applicability is verified and discussed in relation to the existing biological knowledge. This paper intends to highlight the potential role of statistical analysis of all exon microarray data. Our work is an important first step toward development of more advanced statistical technology. Supplementary information and materials are available from http://bonsai.ims.u-tokyo.ac.jp/~yoshidar/IBSB2006_ExonArray.htm.

摘要

可变剪接是一种重要的调控机制,它能产生多种mRNA转录本,这些转录本被转录成功能多样的蛋白质。根据目前的研究,已知由于剪接突变产生的异常转录本会导致15%的遗传疾病。因此,了解可变剪接的调控机制对于识别多种人类疾病的潜在生物标志物至关重要。最近,基因芯片人类外显子1.0 ST阵列的出现使我们能够测量超过一百万个外显子的全基因组表达谱。利用这个新的微阵列平台,功能基因表达的分析不仅可以扩展到检测差异表达基因,还可以扩展到检测在一种或多种实验条件(如肿瘤或正常对照细胞)之间差异观察到的一组特定剪接事件。在本研究中,我们解决了从外显子表达谱中识别差异观察到的剪接变异的统计问题。所提出的方法按以下过程组织:(1)数据预处理,以消除探针强度中的系统偏差。(2)使用方差分析(ANOVA)进行全转录本分析,以识别一组与某种疾病相关的可变剪接的基因座。我们在结直肠癌的外显子表达谱上测试了所提出的统计方法。并结合现有的生物学知识对其适用性进行了验证和讨论。本文旨在强调对所有外显子微阵列数据进行统计分析的潜在作用。我们的工作是朝着开发更先进的统计技术迈出的重要第一步。补充信息和材料可从http://bonsai.ims.u-tokyo.ac.jp/~yoshidar/IBSB2006_ExonArray.htm获取。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验