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The proportion of true null hypotheses in microarray gene expression data.

机译:微阵列基因表达数据中真实无效假设的比例。

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摘要

Microarray technology is extensively used today in many applications. One of its uses is discovering sets of genes that are most likely to be related to cancer. Typically, based on microarray data, a statistical test is conducted for each of thousands of genes simultaneously. In a two-group comparative microarray experiment, an important parameter for controlling the rate of false positives and also for determining the appropriate sample size is the proportion of true null hypotheses (pi0).;To obtain an improved estimation method for pi0, we modify an existing simple method by introducing artificial censoring to p-values. The model is a two-component mixture of a censored Uniform(0,1) and a censored Beta(alpha,1) distribution. The model fitting is achieved through the Expectation Maximization algorithm. In a comprehensive simulation study and applications to experimental data sets, we illustrate the benefits of using our method by comparing its performance to other existing methods.;Furthermore, we develop and study the properties of a likelihood ratio test for pi0 at different combinations of sample size, number of genes, and H0 value of pi0. Maximization of the restricted likelihood is achieved by incorporating a linear constraint of the parameters into the Expectation Maximization algorithm. The p-value of the test is based on a parametric bootstrap approach. We illustrate the usefulness of the test through applications to experimental datasets.
机译:如今,微阵列技术已在许多应用中广泛使用。它的用途之一是发现最可能与癌症有关的基因集。通常,基于微阵列数据,同时对数千个基因中的每个基因进行统计检验。在两组比较微阵列实验中,控制假阳性率以及确定适当样本量的重要参数是真实无效假设(pi0)的比例。为了获得pi0的改进估算方法,我们修改了通过将人工检查引入p值来实现现有的简单方法。该模型是受审查的Uniform(0,1)和受审查的Beta(alpha,1)分布的两部分混合。通过“期望最大化”算法实现模型拟合。在全面的仿真研究中以及在实验数据集上的应用,我们通过将其方法与其他现有方法的性能进行比较来说明使用本方法的好处。此外,我们开发并研究了在不同样本组合下pi0的似然比检验的性质大小,基因数目和pi0的H0值。通过将参数的线性约束合并到“期望最大化”算法中,可以实现受限可能性的最大化。测试的p值基于参数自举方法。我们通过应用到实验数据集来说明测试的有用性。

著录项

  • 作者

    Markitsis, Anastasios.;

  • 作者单位

    The George Washington University.;

  • 授予单位 The George Washington University.;
  • 学科 Biology Biostatistics.;Statistics.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 135 p.
  • 总页数 135
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:37:19

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