Disease Annotations for Variants in Personal Genomes

描述（由申请人提供）：高通量测序技术开始提供完整的个体基因组序列。然而，这些数据在基础研究和个体化医疗临床评价中的应用仍存在重大障碍。一个主要障碍是缺乏对疾病进行变异注释的工具。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。虽然疾病、基因和序列本体论已经存在，但以一种支持有效变体注释的方式系统地将它们相互关联（协调）是一项主要任务。我们将使用最先进的协议进行生物医学本体开发，确保互操作性和可用性来实现这一目标。本应用中提出的研究有三个目的。在第一阶段，我们将协调和相互关联现有的变体和疾病注释本体，特别关注心血管疾病（CVD）。在目标2中，我们将整理由Omicia Inc.编译的由336个CVD疾病基因组成的现有CVD基因集合，以协调本体。在目标3中，我们将注释十个个人基因组的变体和每个变体的含义。我们的计划是从一个概念验证项目开始，开发一个本体论，用于注释与心血管疾病有关的基因中的个人序列变异。在第二阶段，我们打算将本体扩展到更广泛的疾病覆盖范围，利用我们从第一阶段学到的经验教训。这个坚实的逻辑基础将使我们能够构建一套商业实力的变体注释软件，为个人基因组学提供急需的工具。

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.