A novel pattern-based framework for genetic analysis

描述（由申请人提供）： 人类基因组测序，沿着基因组学高通量技术的发展，为我们进一步了解遗传因素在人类健康、疾病和药物反应中的作用提供了前所未有的机会。复杂疾病的基因解剖和药物反应的变异已成为近年来最重要的遗传学研究课题之一。虽然全基因组关联研究被认为有希望确定易感基因负责复杂的疾病，方法，以充分利用基因分型数据仍然缺乏。标准方法通常只考虑有限数量的假设，其中大多数是关于单个基因座或相对较少的基因座的作用，因此不适应可能导致疾病表型和药物反应变化的全部遗传机制。第一基因信托公司(FGT)开发了一种基于模式发现的创新方法来识别多位点遗传关联（enGENIOUS）。2003年，在NCI授予的SBIR第一阶段拨款中成功展示了enGENIOUS的实用性和功能后，FGT打算利用该SBIR第二阶段提案进一步开发其专有的遗传分析方法，并开发一个软件平台来商业化该新方法。沿着其他方法作为通用工具箱。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来展示在全基因组关联分析中将enGENIOUS和选定的常规方法相结合的效用。此外，FGT将开发一个综合软件包，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，一个用于遗传学可扩展Java软件开发工具包（enGENERAYsdk），它实现了对象模型、一个用于存储表型和基因型数据的对象关系数据库以及一个遗传分析工作台（enGENUITY Workbench），该工作台与FGT的enTRUST遗传库系统紧密集成或作为独立应用程序。拟议的软件包将显着提高FGT的竞争优势，导致产生一个重要的新的收入来源，并显着有助于发现复杂疾病的易感基因和药物反应的变化。

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.