2 of 7 EPI4K - Phenotyping Clinical Informatics Core

2 of 7 EPI4K - 表型临床信息学核心

基本信息

批准号：
8533048
负责人：
DANIEL H LOWENSTEIN
金额：
$ 70.22万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8533048
关键词：
Address Affect Bioinformatics Biological Biometry Characteristics Classification Clinical Clinical Informatics Clinical Investigator Common Data Element Communication Consensus Critiques DNA Data Databases Detection Development Diagnosis Diagnostic Disease Documentation Electrophysiology (science)Epilepsy Evaluation Family Family member Genes Genetic Genome Genomics Genotype Goals Hand Human Individual Informatics Interview Life Medical Records Methodology Methods Monitor Neurologic Pathway interactions Patients Personal Satisfaction Phenotype Policies Population Procedures Process Recurrence Research Research Infrastructure Research Personnel Resources Rest Retrieval Risk Sampling Seizures Site Source Structure Study Section System Testing Therapeutic Update Validation Work Writing base career cohort design effective therapy experience genetic analysis improved meetings nervous system disorder neuroimaging phenome prognostic response success tool

项目摘要

DESCRIPTION (provided by applicant): The primary goal of the Epi4K Center Without Walls is to increase understanding of the genetic basis of human epilepsy in order to improve the well-being of patients and family members living with these disorders. This improvement will come in the form of better diagnostics, treatments and cures. To accomplish this goal, Epi4K aims to analyze the genomes of a large number of well-phenotyped epilepsy patients and families collected by investigators from several major research groups. A critical aspect of this enterprise, and the main goal of the Epi4K Phenotyping and Clinical Informatics (PCI) Core described here, is to assemble, organize and validate the phenotypic information on all patients proposed for genomic analysis, and to insure that patients' DNA samples are available to the Epi4K Sequencing, Biostatistics and Bioinformatics (SBB) Core when needed. The availability of well-documented, high quality phenotype data is obviously crucial to the success of all four proposed projects in Epi4K, since the detection of meaningful phenotype:genotype associations will depend highly on phenotype validity. However, achieving this goal in Epi4K will require substantial effort for two main reasons. First, the diagnosis and classification of the epilepsies, including clinical characteristics such as seizure type, seizure semiology, therapeutic response, and additional features such as intellectual and neurological deficits, rests primarily on clinica observations, which are prone to subjectivity and often poorly described or interpreted. Second, Epi4K will assemble at least seven different cohorts of patients collected using varied phenotyping methodologies. To address these challenges, we will capitalize on the substantial experience of the PCI Core investigators, all of whom have devoted considerable portions of their careers to developing methods for accurately phenotyping epilepsy. In addition, through the work of the Epilepsy Phenome/Genome Project (EPGP), we have already created data review systems and a highly efficient informatics infrastructure that can be adapted to the needs of Epi4K. With these resources in hand, the PCI Core seeks to accomplish the following specific aims: 1) to establish standards for documentation of epilepsy phenotypes that can be used reliably across different sites for all subjects undergoing genetic analyses in Epi4K; 2) to design and implement an informatics infrastructure for an Epi4K Phenotype Data Repository and DNA Sample Tracking System; and 3) to validate the phenotype data associated with every DNA sample submitted for genome analyses.

描述（由申请人提供）：没有墙壁的EPI4K中心的主要目标是增加对人癫痫的遗传基础的了解，以改善患有这些疾病的患者和家人的福祉。这种改进将以更好的诊断，治疗方法的形式出现。为了实现这一目标，EPI4K旨在分析许多主要研究小组的研究人员收集的大量癫痫患者和家庭的基因组。该企业的一个关键方面，以及此处描述的EPI4K表型和临床信息学（PCI）核心的主要目标是组装，组织和验证所有提出基因组分析的患者的表型信息，并确保患者的DNA的DNA需要在需要时可用于EPI4K测序，生物统计学和生物信息学（SBB）核心。有据可查的高质量表型数据的可用性对于EPI4K中所有四个项目的成功显然至关重要，因为检测有意义的表型：基因型关联将在很大程度上取决于表型的有效性。但是，在EPI4K中实现这一目标将需要大量努力，这是两个主要原因。首先，癫痫的诊断和分类，包括临床特征，例如癫痫发作类型，癫痫发作学，治疗反应以及诸如智力和神经系统缺陷等其他特征，主要取决于临床观察结果，这些观察值易于主观性，并且经常描述或解释。其次，EPI4K将使用各种表型方法组装至少七个不同的患者同类群体。为了应对这些挑战，我们将利用PCI核心调查人员的大量经验，他们所有人都将大部分职业投入到开发准确表型癫痫的方法上。此外，通过癫痫现象/基因组项目（EPGP）的工作，我们已经创建了数据审核系统和高效的信息学基础架构，可以适应EPI4K的需求。借助这些资源，PCI核心试图完成以下特定目的：1）建立记录癫痫表型的标准，这些标准可以在不同地点可靠地使用EPI4K中的所有受试者使用； 2）设计并为EPI4K表型数据存储库和DNA样品跟踪系统实施信息学基础架构； 3）验证与提交基因组分析的每个DNA样本相关的表型数据。