2 of 7 EPI4K - Phenotyping Clinical Informatics Core

描述（由申请人提供）： Epi 4K无墙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。这种改进将以更好的诊断、治疗和治愈的形式出现。为了实现这一目标，Epi 4K旨在分析由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庭的基因组。该企业的一个关键方面，以及此处描述的Epi 4K表型和临床信息学（PCI）核心的主要目标，是收集，组织和验证所有用于基因组分析的患者的表型信息，并确保患者的DNA样本在需要时可用于Epi 4K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显然对Epi 4K中所有四个拟议项目的成功至关重要，因为检测有意义的表型：基因型关联将高度依赖于表型有效性。 然而，在Epi 4K中实现这一目标需要大量的努力，主要有两个原因。首先，癫痫的诊断和分类， 包括临床特征如癫痫发作类型、癫痫发作症状学、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，这些临床观察倾向于主观性，并且通常描述或解释不佳。 其次，Epi 4K将使用不同的表型分析方法收集至少7个不同的患者队列。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，他们都将相当大的一部分职业生涯投入到开发准确分型癫痫的方法中。此外，通过癫痫表型组/基因组计划（EPGP）的工作，我们已经创建了数据审查系统和高效的信息学基础设施，可以适应Epi 4K的需求。有了这些资源，PCI核心旨在实现以下具体目标：1）建立癫痫表型记录的标准，这些标准可以在不同地点可靠地用于所有接受Epi 4K遗传分析的受试者; 2）设计 并为Epi 4K表型数据储存库和DNA样本跟踪系统建立信息学基础设施;以及3）验证与提交用于基因组分析的每个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.