NC GENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing

描述(申请人提供)：基因组学领域的技术发展现在为以快速和负担得起的方式确定个人基因组的完整序列提供了机会。这种“全基因组测序”及其更简单的推论--“全外显子组测序”(WES)已经成为强有力的研究工具。这项技术发展的下一步自然是将其直接应用于临床 竞技场。然而，尽管这种技术具有相当大的临床前景，但在应用它并为患者带来实际好处方面存在巨大挑战。在这项提案中，我们概述了一种高度跨学科的方法来识别、面对和克服必须满足的主要挑战，以便在临床医学中实施深度测序技术。目标1将探索WES作为一种诊断工具在广泛的患者护理中的使用，评估其性能，确定可指导其应用的关键临床特征，并衡量此类信息对患者和提供者的影响。AIM 2将解决WES临床应用中最紧迫的挑战之一：不可避免地产生“附属品”或“旁观者”信息。将开发教育材料，使患者能够就适当的结果返回做出决定，并将在提供者、实验室和患者层面评估附属信息的影响。目标3将解决基因组医学临床应用中的第三个主要挑战，即如何处理海量信息。将创建和改进面向临床的“入库”结构，以便在实际类别中对数据进行分类、存储和传输，以便理解产生的大量数据。最后，当我们站在基因组医学的尖端时，我们必须确保所有人都能享受到它的好处。因此，Aim 4将在传统上代表性不足的人群中开展临床工作，以确定将这一新工具临床转化为尽可能广泛的人群的特殊机会和挑战。我们的最终目标是建立一套最佳实践来指导未来实施强大的基因组技术，以真正和实际地改善人类健康。

DESCRIPTION (provided by applicant): Technological developments in the field of genomics now afford the opportunity to define the complete sequence of an individual's genome in a rapid and affordable manner. Such "whole genome sequencing" and its simpler corollary, "whole exome sequencing" (WES), have already established themselves as powerful research tools. The natural next step in the evolution of this technology is its direct application in the clinical arena. However, while such technology holds considerable clinical promise, tremendous challenges exist in applying it and deriving practical benefit to patients. In this proposal we outline a highly interdisciplinary approach to identifying, confronting and overcoming the major challenges which must be met in order to implement deep sequencing technology in clinical medicine. Aim 1 will explore the use of WES as a diagnostic tool in the care of a broad array of patients, evaluate its performance, identify critical clinical characteristics which can guide its application and measure the impact of such information on patients and providers. Aim 2 will tackle one of the most pressing challenges in the clinical application of WES: the inevitable generation of "collateral" or "bystander" information. Educational materials will be developed to enable patients to make decisions about appropriate return of results and the impact of collateral information will be assessed at the level of the provider, laboratory and patient. The third major challenge in clinical implementation of genomic medicine, how do deal with vast amounts of information, will be addressed by Aim 3. A clinically oriented "binning" structure will be created and refined for classifying, storing and transmitting data within practical categories so as to make sense of the large amounts of data generated. Finally, as we stand on the cusp of genomic medicine, we must ensure that all have access to its benefits. Thus, Aim 4 will pursue clinical WES in traditionally underrepresented populations to identify special opportunities and challenges in the clinical translation of this new tool to the broadest possible population. Our ultimate aim is to establish a set of best practices to guide future implementation of robust genomic technologies for the real and practical betterment of human health.