ImplementatioN ScIence for Genomic Health Translation (INSIGHT)

项目总结 尽管在基因发现方面取得了巨大的进步，精准医学的概念也上升到了 科学术语，如国家AllfUS倡议，翻译这一丰富的科学知识 随着基因组学信息的广泛实施成为标准，患者护理的标准化进程一直很缓慢 临床实践面临着管理速度上的巨大差距。 这个名为基因组健康翻译实施科学(Insight)的项目的目标是建立一个 在可扩展基因测试、数据的实现科学原则指导下的可概化范例 整合、结果解释和临床决策支持，指导常见并发症的常规保健 疾病特征，如癫痫。癫痫是一种复杂的神经样本病，临床表现多种多样。 基因发现已经发展到DNA诊断容易处理的程度的环境，证据- 以临床护理为基础和有利的。鉴于我们的多学科小组在 将基因组信息整合到临床环境中(例如“心脏护理”项目)和开发 健康数据管理平台(如专门针对癫痫的定制电子病历[EMR]) -缩影)，我们将在之前建立的证据和基础设施的基础上，成功地整合临床 将基因组学引入临床护理，以及创建电子病历工具，帮助临床进行基于基因组学的决策。 首先，我们将识别和整合疾病易感变异、药物-基因药物基因组学对和深度 用于癫痫患者护理的可供干预的基因组知识库(IRGK)中的表型信息 作为一个可概括的范例。在这样做的过程中，我们将建立一条途径，将这一机构的翻译 精准干预患者护理方面的知识。第二，我们将把iRGK整合到一个 现有缩影，从而创建了一个健康信息学平台(缩影+)；我们将进一步链接现有的 临床基因组学报告系统(NEPOUNT)和EMPLOME+。将创建临床决策支持界面 在缩影+，让精准医疗成为可能。这两个系统的结合将作为一种 范例洞察范式适用于其他疾病领域。试行测试洞察力方法和 缩影+接口，我们将从德克萨斯州综合癫痫计划中招募120名患者，该计划 在种族和经济上都是多样化的。 我们相信，这种特定领域的、实用的、但可概括的洞察方法将有助于催化一条途径 加速将基因组知识转化为有效的患者护理干预措施。下降的条件 与癫痫同属一类的疾病包括但不限于心肌病、某些肾脏和消化系统疾病 疾病，以及家族性或早发性癌症的清单。完成此R21研究还将使我们能够生成 “推进基因组医学研究”计划未来R01申请的初步结果。

PROJECT SUMMARY Despite enormous progresses in gene discovery and elevation of the concept of precision medicine into the scientific vernacular, such as the national AllofUS initiative, translation of this rich body of scientific knowledge into standard patient care has been slow, with broad implementation of genomics information into standard clinical practice facing a significant gap in management velocity. The goal of this project, ImplementatioN ScIence for Genomic Health Translation (INSIGHT), is to establish a generalizable paradigm guided by the principles of implementation science for scalable genetic testing, data integration, results interpretation and clinical decision support to guide routine health care for common complex disease traits, such as epilepsy. Epilepsy is a complex neuro-exemplar disease presenting in various clinical settings, in which genetic discovery has progressed to a point where DNA diagnostics is tractable, evidence- based, and advantageous for clinical care. Given the track-record of success of our multidisciplinary group in both integration of genomic information into clinical settings (such as the “HeartCare” project) and development of health data management platforms (such as an epilepsy-specific bespoke Electronic Medical Records [EMR] - EpiToMe), we will build on evidence and infrastructure established previously, to successfully integrate clinical genomics into clinical care, as well as create EMR tools that aid clinical, genomics based decision-making. First, we will identify and integrate disease susceptibility variants, drug-gene pharmacogenomics pairs, and deep phenotypic information into an intervention-ready genomic knowledgebase (iRGK) for patient care using epilepsy as a generalizable paradigm. In doing so, we will establish a pathway to place this body of translational knowledge in the context of precision intervention in patient care. Second, we will incorporate iRGK into an existing EpiToMe, resulting in creation of a health informatics platform (EpiToMe+); we will further link an existing clinical genomics reporting system (Neptune) and EpiToMe+. Clinical decision support interfaces will be created in EpiToMe+ to enable the practice of precision medicine. The coupling of the two systems will serve as an exemplar INSIGHT paradigm applicable to other disease areas. To pilot test the INSIGHT approach and the EpiToMe+ interfaces, we will enroll 120 patients drawn from the Texas Comprehensive Epilepsy Program, which is ethnically and economically diverse. We believe that this domain-specific, practical but generalizable INSIGHT approach will help catalyze a pathway to accelerate translation of genomic knowledge into impactful interventions in patient care. Conditions that fall under the same umbrella as epilepsy include but are not limited to cardiomyopathies, certain kidney and digestive disorders, and a list of familial or early onset cancers. Accomplishing this R21 study will also allow us to generate preliminary results for a future R01 application for the “Advancing Genomic Medicine Research” program.