2 of 7 EPI4K - Phenotyping Clinical Informatics Core

2 of 7 EPI4K - 表型临床信息学核心

• 批准号: 8240658
• 负责人: DANIEL H LOWENSTEIN
• 金额: $ 81.48万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 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/8240658
• 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

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. PUBLIC HEALTH RELEVANCE: Epilepsy is one of the most common neurological disorders in humans, affecting up to 3% of the population. Although there is a strong genetic component for epilepsy, there are still only a few genes known. The Epi4K project will identify new genes and genetic pathways in epilepsy and will directly benefit individuals with epilepsy and their families through improved diagnostic, prognostic and recurrence risk information. Epi4K will also advance our understanding of the biological basis of epilepsy, which is essential for the development of new and effective treatments, as well as cures. Disclaimer: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation, based upon the group's discussion, there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore, the critiques may not fully reflect the final opinions of th individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.

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。 公共卫生相关性：癫痫是人类最常见的神经系统疾病之一，影响了多达3％的人群。 尽管癫痫的遗传成分很强，但仍然只有少数几个基因。 EPI4K项目将确定癫痫中的新基因和遗传途径，并通过改进诊断，预后和复发风险信息直接使患有癫痫病及其家人的人受益。 EPI4K还将提高我们对癫痫生物学基础的理解，这对于开发新的有效疗法以及治疗方法至关重要。 免责声明：请注意，以下批评是由审稿人在研究部分会议之前准备的，并以本质上未经编辑的形式提供。 尽管审稿人有机会根据小组的讨论来更新或修改其书面评估，但不能保证在会议上讨论后对个人批评进行了更新。 因此，批评可能无法完全反映在小组讨论结束时，个人审稿人的最终意见或小组的最终多数意见。因此，讨论的简历和摘要是审稿人在会议上实际认为至关重要的最终词。