CIF: Small: Collaborative Research: A General Theory of Group Testing for Genotyping

CIF：小型：协作研究：基因分型群体测试的一般理论

• 批准号: 1217894
• 负责人: Alexander Barg
• 金额: $ 24.98万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1217894&HistoricalAwards=false
• 关键词: CIF; Small; Collaborative; Research; General

Next generation high-throughput sequencing devices have brought the promise of personalized genotyping to the field of human genomics. Advances in personalized genotyping depend on developments of procedures for cost-efficient large-scale association studies. Such large-scale experiments and studies face a number of obstacles related to constraints imposed by bioengineering systems and test subjects, including a) the restriction that tests have to be performed with small samples of individuals' genetic material; b) the constraint that subjects have to be multiplexed, so that genetic sequences have to be barcoded; c) the fact that the outcomes of the tests are semi-quantitative; d) the reality that many tests have to be performed within groups of related individuals, thereby significantly increasing the cost of screening whole families; e) the fact that tests have to deal with the challenge of variant discovery and individuals that may exhibit different gene copy numbers. A natural way to overcome these and many other obstacles is to perform genotyping via group testing.The goals of this project include developing of a comprehensive, yet analytically or computationally tractable general theory of group testing for genotyping. The proposed theory will answer the unique challenges arising in genotyping by sequencing, although parts of the theory may find independent applications in areas as diverse as constrained multiple access channel analysis, fingerprinting and identification coding, and error-control coding. In particular, the investigators introduce several new models into the field of group testing, including subjects with different types and strengths, semi-quantitative testing, two-dimensional pooling, and Poisson probabilistic testing.

下一代高通量测序设备为人类基因组学领域带来了个性化基因分型的希望。个性化基因分型的进步取决于具有成本效益的大规模关联研究程序的发展。这种大规模的实验和研究面临着许多与生物工程系统和测试对象所施加的限制有关的障碍，包括a）必须使用个体遗传物质的小样本进行测试的限制； b) 受试者必须被多重化的限制，因此必须对基因序列进行条形码标记； c) 测试结果是半定量的； d) 事实上，许多检测必须在相关个体的群体内进行，从而大大增加了筛查整个家庭的成本； e) 测试必须应对变异发现和可能表现出不同基因拷贝数的个体的挑战。克服这些和许多其他障碍的自然方法是通过群体测试进行基因分型。该项目的目标包括开发一种全面的、但分析或计算上易于处理的基因分型群体测试的一般理论。所提出的理论将回答通过测序进行基因分型中出现的独特挑战，尽管该理论的部分内容可能会在受限多路访问通道分析、指纹识别和识别编码以及错误控制编码等多种领域中找到独立的应用。特别是，研究人员在群体测试领域引入了几种新模型，包括不同类型和强度的受试者、半定量测试、二维池化和泊松概率测试。