Disease Annotations for Variants in Personal Genomes

个人基因组变异的疾病注释

• 批准号: 8002144
• 负责人: Karen Louise Eilbeck
• 金额: $ 14.92万
• 依托单位: FABRIC GENOMICS INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2012-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8002144
• 关键词: Area; Arts; Basic Science; Cardiovascular Diseases; Categories; Clinical; Collection; Computer software; Data; Data Set; Development; Disease; Ensure; Foundations; Generations; Genes; Genetic; Genetic Variation; Genome; Genomics; Goals; Health; Hereditary Disease; Human; Individual; Learning; Literature; Location; Manuals; Medicine; Molecular Diagnostic Testing; Mutation; Nature; Ontology; Other Genetics; Phase; Process; Proteins; Protocols documentation; Public Health; Publishing; Reporting; Reproductive Health; Research; Resources; Solutions; Structural Genes; System; Technology; Terminology; Testing; Variant; Vocabulary; Work; arm; base; biomedical ontology; clinically relevant; commercialization; disease classification; genome sequencing; innovation; interoperability; prognostic; prototype; public health relevance; research clinical testing; tool; tool development; tumorigenesis; usability

DESCRIPTION (provided by applicant): High-throughput sequencing technologies are beginning to deliver complete individual genome sequences. However, significant barriers still obstruct the use of these data for basic research and in clinical evaluation for personalized medicine. One major barrier is the absence of tools for variant annotation with respect to disease. Our goal is to overcome this barrier by creating for sequence variants a suite of tools similar to those that exist for gene annotation. Although disease, gene and sequence ontolgies already exist, systematically interrelating (harmonizing) them to one another in a manner that will support effective variant annotation is a major task. We will use state of the art protocol for biomedical ontology development, ensuring interoperability and usability to achieve this goal. The research proposed in this application has three aims. In Phase I we will harmonize and interrelate existing ontologies for variant and disease annotation, with a specific focus on cardiovascular disease (CVD). In Aim 2 we will curate an existing CVD gene collection compiled at Omicia Inc. consisting of 336 CVD disease genes to the harmonized ontology. In Aim 3 we will annotate the variants and implications of each variation for ten personal genomes. Our plan is to begin with a proof-of-concept project to develop an ontology for annotating personal sequence variants in genes implicated in CVD. In phase II we intend to expand the ontology to a broader coverage of disease, utilizing the lessons we learn from phase I. This firm logical foundation will allow us to build a suite of commercial strength software for variant annotation to provide a much needed tool for personal genomics. PUBLIC HEALTH RELEVANCE: This project will produce a modular, harmonized ontology for the description of personal genomic sequence variants with respect to cardiovascular disease (CVD). This will in turn provide a means to generate detailed, clinically relevant genetic-signature reports. This work will be preformed in partnership with Omicia Incorporated. Omicia's goal is to provide content and analysis tools for molecular diagnostic tests using personal genome sequences. The tools produced by this project will promote better public health and provide significant commercial opportunities.

描述（由申请人提供）：高通量测序技术开始提供完整的单个基因组序列。但是，重大障碍仍然阻碍这些数据用于基础研究和个性化医学的临床评估。一个主要的障碍是缺少有关疾病变异注释的工具。我们的目标是通过为序列变体创建一套类似于基因注释的工具来克服这一障碍。尽管已经存在疾病，基因和序列安大哥，但以支持有效变体注释的方式进行系统的相互关联（和谐）是一项主要任务。我们将使用最先进的协议来进行生物医学本体论开发，以确保实现这一目标的互操作性和可用性。本应用程序中提出的研究具有三个目标。在第一阶段，我们将协调和相互关联的变异和疾病注释的现有本体，特别关注心血管疾病（CVD）。在AIM 2中，我们将在Omicia Inc.汇编的现有CVD基因收集。由336个CVD疾病基因组成的统一本体论。在AIM 3中，我们将注释每个变异对十个个人基因组的变体和含义。我们的计划是从一个概念验证项目开始，以开发一个本体，以注释与CVD有关的基因中的个人序列变体。在第二阶段，我们打算利用我们从第一阶段学习的课程将本体论扩展到更广泛的疾病覆盖范围。这项公司的逻辑基础将使我们能够构建一套商业强度软件，用于变异注释，为个人基因组学提供急需的工具。 公共卫生相关性：该项目将产生一个模块化的，统一的本体论，以描述有关心血管疾病（CVD）的个人基因组序列变体。反过来，这将提供一种产生详细的，临床相关的遗传签名报告的方法。这项工作将与Omicia Incorporated合作进行。 Omicia的目标是使用个人基因组序列提供分子诊断测试的内容和分析工具。该项目生产的工具将促进更好的公共卫生并提供大量商业机会。