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Pathway-based statistical methods for analyzing microarray data.

机译:基于通路的统计方法,用于分析微阵列数据。

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摘要

Microarray technology has flourished in the past decade and has been used extensively for functional genomic analysis. Tremendous research progress has been made in microarray data collection and analysis throughout this period. As microarray technology advances, subtle changes in the data are more common. Pathway analysis allows researchers to uncover biological meaningful sets of genes. It also has its advantages over widely used single gene-based analyses which are unable to take into account the dependencies between genes and are prone to multivariate testing issues. Several pathway-based methods have recently been proposed. However, these methods usually do not give consistent results, leaving room for the development of more efficient statistical methods and computational tools to better detect important pathways from microarray data. In this dissertation, we will first tackle the challenge of how to apply classification and regression methods to pathway-based analysis. Secondly, we will develop methods for clustering pathways and investigate possible interactions between them. The third project makes use of a random effects model for analyzing a pair of pathways. Lastly, we will propose a regularized shrinkage-based diagonal discriminant analysis for small sample size microarray data. Pathway-based tests for microarray data show great promise as a tool for biomedical research. Informative pathways may aid in the detection of disease at an early stage, help discover novel biomarkers and pinpoint target genes for possible interventions. Therefore, being able to identify important pathways associated with disease provides a new avenue for disease identification, prevention and diagnostics and has substantial public health impact.
机译:在过去的十年中,微阵列技术蓬勃发展,并已广泛用于功能基因组分析。在此期间,微阵列数据收集和分析方面已取得了巨大的研究进展。随着微阵列技术的发展,数据中的细微变化更加普遍。途径分析使研究人员可以发现生物学上有意义的基因集。与广泛使用的基于单基因的分析相比,它还具有优势,后者无法考虑基因之间的依赖性,并且容易出现多变量测试问题。最近已经提出了几种基于途径的方法。然而,这些方法通常不能给出一致的结果,为开发更有效的统计方法和计算工具以更好地从微阵列数据中检测重要途径留下了空间。在本文中,我们将首先解决如何将分类和回归方法应用于基于路径的分析的挑战。其次,我们将开发聚类途径的方法并研究它们之间可能的相互作用。第三个项目利用随机效应模型来分析一对路径。最后,我们将针对小样本大小的微阵列数据提出基于正则收缩的对角判别分析。基于通路的微阵列数据测试显示了作为生物医学研究工具的巨大希望。信息性途径可能有助于早期发现疾病,帮助发现新的生物标志物并查明可能的干预措施的靶基因。因此,能够确定与疾病相关的重要途径为疾病的鉴定,预防和诊断提供了一条新途径,并具有重大的公共卫生影响。

著录项

  • 作者

    Pang, Herbert Hei Man.;

  • 作者单位

    Yale University.;

  • 授予单位 Yale University.;
  • 学科 Biology Biostatistics.;Biology Bioinformatics.;Health Sciences Public Health.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 198 p.
  • 总页数 198
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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