2 of 7 EPI4K - Phenotyping Clinical Informatics Core

描述(申请人提供)：无墙Epi4K中心的主要目标是增加对人类癫痫遗传基础的了解，以改善患有这些疾病的患者和家庭成员的福祉。这种改善将以更好的诊断、治疗和治愈的形式出现。为了实现这一目标，Epi4K旨在分析来自几个主要研究小组的研究人员收集的大量表型良好的癫痫患者和家族的基因组。这项事业的一个关键方面，也是这里描述的Epi4K表型和临床信息学(PCI)核心的主要目标是组装、组织和验证所有建议进行基因组分析的患者的表型信息，并确保当需要时，患者的DNA样本可供Epi4K测序、生物统计和生物信息学(SBB)核心使用。由于检测有意义的表型：表型相关性将高度依赖于表型的有效性，因此，获得记录良好、高质量的表型数据显然是Epi4K中所有四个拟议项目成功的关键。然而，在Epi4K中实现这一目标需要付出大量努力，主要原因有两个。首先，癫痫的诊断和分类， 包括临床特征，如癫痫类型、癫痫症状、治疗反应，以及其他特征，如智力和神经缺陷，主要依赖于临床观察，这些观察容易带有主观性，往往描述或解释不当。其次，Epi4K将汇集至少七个不同的患者队列，这些患者使用不同的表型方法收集。为了应对这些挑战，我们将利用PCI核心研究人员的丰富经验，他们都在职业生涯中投入了相当一部分时间来开发准确的癫痫表型鉴定方法。此外，通过癫痫表现组/基因组计划(EPGP)的工作，我们已经创建了数据审查系统和能够适应Epi4K需求的高效信息学基础设施。有了这些资源，PCI Core试图实现以下具体目标：1)建立癫痫表型记录的标准，这些标准可以跨不同地点可靠地用于所有接受Epi4K基因分析的受试者；2)设计 并为Epi4K表型数据库和DNA样本跟踪系统实施信息基础设施；以及3)验证与提交进行基因组分析的每个DNA样本相关的表型数据。

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.