A novel pattern-based framework for genetic analysis

描述(由申请人提供)： 人类基因组测序，以及基因组学中高通量技术的发展，为我们提供了一个无与伦比的机会来促进我们对遗传因素在人类健康、疾病和药物反应中的作用的理解。复杂疾病和药物反应变异的基因解剖已成为近年来最重要的遗传学研究课题之一。尽管全基因组关联研究被认为有望识别导致复杂疾病的易感基因，但仍缺乏充分利用基因分型数据的方法。标准方法通常只考虑有限数量的假说，其中大多数是关于单个基因座或相对少数基因座的影响，因此不能适应可能导致疾病表型和药物反应变化的全部遗传机制。First Genetic Trust Inc.(FGT)开发了一种基于模式发现的创新方法来识别多基因座遗传关联(EnGENIOUS)。在2003年NCI授予的SBIR第一阶段拨款中成功展示了enGENIOUS的效用和力量后，FGT打算利用这项SBIR第二阶段的提案进一步开发其专有的基因分析方法，并开发一个软件平台，将新方法与其他方法一起商业化，作为一个通用工具箱。在该项目的第二阶段，FGT将在全基因组范围内扩展enGENIOUS，并将通过使用来自FGT合作者的全基因组数据集，展示将enGENIOUS与选定的传统方法结合在一起进行全基因组关联分析的实用性。此外，FGT将开发一个全面的软件包，包括用于表示概念(如数据、分析、结果等)的对象数据模型。在遗传分析中，用于实现对象模型的可扩展的Java遗传学软件开发工具包(EnGENUITYsdk)，用于存储表型和基因数据的对象关系数据库，以及与FGT的委托遗传库系统紧密集成或作为独立应用程序的遗传分析工作台(enGENUITY工作台)。拟议的软件包将显著增强FGT的竞争优势，产生一个重要的新收入来源，并为发现复杂疾病的易感基因和药物反应的变异做出重大贡献。

DESCRIPTION (provided by applicant): The sequencing of the human genome, along with the development of high-throughtput technologies in genomics, provides an unparalleled opportunity to advance our understanding of the roles of genetic factors in human health, disease, and drug response. Genetic dissection of complex disease and variations of drug response has become one of the most important genetic research topics in recent years. Although genome-wide association studies are thought to hold the promise to identify susceptibility genes responsible to complex diseases, methodologies to take full advantage of the genotyping data are still lacking. Standard approaches typically only consider a limited number of hypotheses, most of which are on the effect of a single locus or a relative few loci, therefore do not accommodate the full range of genetic mechanisms that may contribute to the disease phenotype and variations of drug response. First Genetic Trust Inc. (FGT) has developed an innovative pattern discovery-based method to identify multi-locus genetic associations (enGENIOUS). Upon successful demonstration of the utilities and power of enGENIOUS in a SBIR phase I grant awarded by NCI in 2003, FGT intends to use this SBIR phase II proposal to further develop its proprietary genetic analysis methodology as well as to develop a software platform to commercialize the novel methodology along with others as a general tool box. In phase II of the project, FGT will extend enGENIOUS on a genome-wide scale, and will demonstrate the utility of combining enGENIOUS and selected conventional methodologies in whole genome association analysis by using whole-genome datasets from a FGT collaborator. Additionally, FGT will develop a comprehensive software package including an object data model for the representation of concepts (like data, analyses, results, etc.) in genetic analysis, an extensible Java software development toolkit for genetics (enGENUITYsdk) that implement the object model, an object-relational database for storing phenotypic and genotypic data, and a genetic analysis workbench (enGENUITY Workbench) that is either tightly integrated with FGT's enTRUST Genetic Banking System or as a stand-alone application. The proposed software package will significantly enhance the competitive advantage of FGT, result in the generation of an important new source of revenue, and significantly contribute to the discovery of susceptibility genes in complex diseases and variation of drug response.