Clinically Relevant Genome Variation Database

临床相关基因组变异数据库

基本信息

批准号：
9047616
负责人：
Carlos Daniel Bustamante
金额：
$ 24.95万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-23 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9047616
关键词：
Algorithms American Bioinformatics Biological Assay Cataloging Catalogs Classification Clinical Clinical Data Clinical Practice Guideline Clinical Research Collaborations Communities Consensus DNA Data Data Sources Databases Deposition Development Disease Disease Pathway Documentation Ensure Epidemiology Funding Genes Genetic Genetic Counseling Genetic Population Study Genetic screening method Genetic study Genome Genomics Goals Guidelines Health Human Genetics Internet Knowledge Laboratories Lesion Letters Literature Machine Learning Medical Medical Genetics Medicine Mendelian disorder Methodology Molecular Mutation National Human Genome Research Institute North Carolina Nucleotides Online Mendelian Inheritance In Man Ontology Patients Phase Population Population Genetics Process Professional Organizations Research Research Personnel Resources Services Site Societies Test Result Testing Translating United States National Institutes of Health Universities Update Variant Work base clinical care clinical sequencing clinically relevant college data exchange data mining design empowered gene function genetic counselor genetic variant genome analysis genome sequencing genome-wide improved knowledge base medical schools meetings novel research clinical testing response user-friendly web services working group

项目摘要

We propose to create the world's premier database of genetic variants relevant to clinical care (Clinically Relevant Genetic Variants Resource or CRVR). We will provide transparent data synthesis and consensus opinion on the clinical utility of a given genetic variant across a spectrum of genetic lesions including single nucleotide changes, small indels and structural variants. We will integrate with ClinVar, PharmGKB, and OMIM and draw upon NHGRI initiatives including the Genome Sequencing and Analysis and Mendelian Disorders Sequencing Centers, and the Clinical Sequencing Exploratory Research Centers. We will work closely with other CRVR sites and NHGRI funded initiatives to improve deposition of data from clinical laboratories. Our database will be built through three Aims. Aim 1 will engage and energize the clinical genomics community around CRVR efforts. We will partner with the other CRVR and U41 investigators in this activity as they will focus on engagement of professional societies, clinical testing laboratories, and the broader clinical genomics community to ensure creation of a CRVR resource that meets anticipated community needs including assembly of Disease-Specific and Mutation Type Working Groups (DSWGs and MTWGs) comprised of expert clinical geneticists and molecular diagnosticians to establish metrics for the initial classification of variants and integration of guidelines from professional organizations. Aim 2 will involve creation of a CRVR CoreDB resource through expert review of the existing literature, locus databases, and NHGRI initiatives. We will disseminate consensus findings on clinically relevant genetic variants and the clinical implications of these variants, with supporting evidence and documentation of the consensus process. Information will be aggregated using standard ontologies and advanced methodologies for handling heterogeneous data to create a Core Database (CoreDB). The consensus of expert review will be disseminated through a user-friendly web Portal (vetted by Genetic Counseling WG), web services for data mining, and consensus clinical guidelines to the appropriate clinical and research communities. The results will be organized by gene, variant, disease, pathway, and literature. Supporting evidence will also be curated and disseminated, and the resource will be updated continuously as new information accumulates. Aim 3 will involve deployment of machine-learning algorithms for semi- automatic identification of putative Clinically Relevant Variants (CRVs). We will undertake data mining of the clinical and epidemiological genetics literature and existing databases to identify putative clinically important variants. This will involve mining data from ClinVar, OMIM, CSER, and the Mendelian centers aggregated in Aim 2. The Working Groups formed in Aim 1 will establish criteria and oversee curators vetting variants. We will develop and optimize disease- and gene-specific machine learning algorithms to facilitate rapid classification of variants based on data provided by genetic testing services via ClinVar. We will integrate population-genetic data inferred from at least 25 reference populations from the 1000 Genomes Project and other large endeavors into our machine learning approaches so as to infer the global relevance of CRVs discovered here.

我们建议创建与临床护理相关的遗传变异数据库（临床上）相关的遗传变体资源或CRVR）。我们将提供透明的数据综合和共识关于给定遗传变异的临床效用的意见，包括单个遗传病变核苷酸变化，小插入和结构变体。我们将与Clinvar，PharmGKB和 OMIM并借鉴NHGRI计划，包括基因组测序和分析以及Mendelian 疾病测序中心和临床测序探索性研究中心。我们将工作与其他CRVR站点和NHGRI资助的计划紧密联系，以改善临床数据的数据实验室。我们的数据库将通过三个目标构建。 AIM 1将参与并激发临床基因组学围绕CRVR努力。我们将与其他CRVR和U41调查人员合作这项活动将着重于专业社会的参与，临床测试实验室以及更广泛的临床基因组学社区，以确保创建符合预期社区的CRVR资源包括疾病特异性和突变类型工作组的组装（DSWG和MTWG）的需求由专家临床遗传学家和分子诊断者组成，以建立初始的指标变体的分类和专业组织的指南集成。 AIM 2将涉及通过对现有文献，基因座数据库的专家审查创建CRVR CoreDB资源，和NHGRI计划。我们将在临床相关的遗传变异和这些变体的临床意义，并提供了证据和共识过程的证据。信息将使用标准本体论和高级方法进行汇总异质数据创建一个核心数据库（CoredB）。专家审查的共识将是通过用户友好的Web门户（由遗传咨询WG审查），Web服务进行数据传播采矿以及适当的临床和研究社区的共识临床指南。结果将由基因，变体，疾病，途径和文献组织。支持证据也将策划并传播，随着新信息的积累，资源将不断更新。目标3意志涉及部署机器学习算法，以半自动识别推定临床相关变体（CRV）。我们将进行临床和流行病学的数据挖掘遗传学文献和现有数据库，以识别推定的临床上重要变体。这将涉及来自Clinvar，Omim，CSER和Mendelian中心的采矿数据在AIM 2中汇总。工作组在AIM 1中形成的将建立标准并监督策展人审查变体。我们将开发和优化疾病和基因特异性机器学习算法，以促进基于变体的快速分类基因测试服务通过Clinvar提供的数据。我们将整合从AT推断的人口基因数据至少有25个来自1000个基因组项目的参考人群和我们机器的其他大型努力学习方法是为了推断此处发现的CRV的全球相关性。