Multiple Testing: Further Development Of Theory And Methodology

多重测试：理论和方法的进一步发展

• 批准号: 0603868
• 负责人: Sanat Sarkar
• 金额: $ 16.99万
• 依托单位: Temple University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0603868&HistoricalAwards=false
• 关键词: Multiple; Testing; Further; Development; Theory

MULTIPLE TESTING: FURTHER DEVELOPMENT OF THEORY AND METHODOLOGY The primary goal of the investigator in this project is further development of statistical theory and methodology for problems in multiple hypothesis testing. Having realized that the traditional idea of controlling the familywise error rate (FWER) is too stringent to use when large number of hypotheses are tested, researchers have recently focused on defining less stringent error rates and developing methods that control them. The false discovery rate (FDR) is the first of these receiving considerable attention, even though there are still a number of important related issues that are yet to be answered. The probabilities of rejecting at least a number more than one and the false discovery proportion exceeding a certain threshold are the two most recently introduced concepts that generalize the FWER and represent meaningful alternatives to the FDR. While some methods controlling them have been suggested very recently, the potential to developing newer and more powerful procedures is revealed by some recent work by the investigator. The development of such new procedures and investigative studies comparing them to related methods, theoretically as well as empirically, will be one major thrust of the present research. When testing multiple null hypotheses against two-sided alternatives, making directional decisions for the alternative hypotheses corresponding to the rejected ones with a control of false directional rejections is often desired. While such a procedure has been recently put forward in the framework of the FDR, there is a good potential of developing newer procedures in light of some work of the investigator together with students and colleagues. The development of such new procedures will be the second major thrust of this research.The results from this research will be of importance to virtually any statistical investigation where questions are posed in terms of testing several hypotheses. One particular area of application is DNA microarrays which are a new and promising biotechnology that can monitor expression levels in cells for thousands of genes simultaneously. The identification of differentially expressed genes is an important and common question in these experiments. The biological question of differential expression is framed as a statistical problem of multiple hypotheses testing: the simultaneous test for each gene of the null hypothesis that the expression levels do not associate with the responses or covariates of interest. Developing a statistical procedure of discovering the genes that are differentially expressed by controlling statistical measures of false discoveries or false non-discoveries at a desired level is one of the central issues in such a problem. Another area of application is pharmaceutical investigations where multiple testing techniques are routinely used in dose-response study or in evaluating a drug's efficacy over a standard drug or placebo. This research has the potential to generate collaborations with researchers in the biopharmaceutical industry and medical schools. It would also benefit education through training of graduate students, incorporation of the developed methodologies in statistics courses, and writing textbooks.

多重检验：理论和方法的进一步发展本项目研究人员的主要目标是进一步发展多重假设检验问题的统计理论和方法。在意识到传统的控制家庭错误率(FWER)的想法太严格而不能在测试大量假设时使用后，研究人员最近专注于定义不那么严格的错误率并开发控制它们的方法。错误发现率(FDR)是受到相当大关注的第一个问题，尽管仍有一些重要的相关问题尚未得到回答。拒绝一个以上数字的概率和超过某个阈值的错误发现比例是最近引入的两个概念，它们推广了FWER，代表了FDR的有意义的替代方案。虽然最近已经提出了一些控制它们的方法，但研究人员最近的一些工作揭示了开发更新和更强大的程序的潜力。开发这种新的程序，并从理论上和经验上将它们与相关方法进行比较，这将是本研究的一个主要方向。当针对双边选择检验多个无效假设时，通常希望对与被拒绝的假设相对应的替代假设做出方向决定，并控制错误的方向拒绝。虽然最近在民主变革进程的框架内提出了这样一个程序，但根据调查员与学生和同事一起开展的一些工作，仍有很好的潜力开发新的程序。这种新程序的开发将是这项研究的第二个主要主题。这项研究的结果将对几乎任何以检验几个假设的方式提出问题的统计调查都具有重要意义。一个特别的应用领域是DNA微阵列，这是一种新的、有前途的生物技术，可以同时监测细胞中数千个基因的表达水平。在这些实验中，差异表达基因的鉴定是一个重要而常见的问题。差异表达的生物学问题被框架化为多个假设检验的统计学问题：对零假设的每个基因的同时检验，即表达水平与感兴趣的反应或协变量无关。开发一种统计程序来发现差异表达的基因，方法是将错误发现或错误未发现的统计度量控制在所需的水平上，这是此类问题的中心问题之一。另一个应用领域是药物调查，在剂量反应研究中或在评估一种药物相对于标准药物或安慰剂的疗效时，经常使用多种测试技术。这项研究有可能与生物制药行业和医学院的研究人员合作。它还将通过培训研究生、将已开发的方法纳入统计课程和编写教科书而受益于教育。