CTSA RC2 Program at University of Utah: A Translational Platform for Rapid Genomic Medicine

摘要 虽然过去十年见证了基础基因组研究的爆炸性增长，但临床应用 基因组医学仍然难以捉摸。该专业化创新计划(SIP)将识别和克服 阻碍快速基因组医学发现的翻译科学的障碍 整合基础设施、技术和策略，以设计和开发快速基因组诊断 平台，使用新生儿重症监护病房(NICU)作为实验室。新兴的临床指南支持 快速全基因组测序在NICU的价值和应用，然而多重障碍阻碍了 在护理点广泛使用这项技术。具体地说，(1)稀有孟德尔不到一半 使用目前的测序和分析技术可以解决疾病；(2)工业电子健康 基于记录(EHR)的基因组医学应用基本上是不存在的，缺乏与EHR接口的 允许可视化和基于团队的基因组测序解释的平台；(3)翻译 目前缺乏将基因组医学应用于临床护理的科学策略。要克服这些障碍 障碍，SIP将设计和开发一个创新的、协作的、以患者为中心的、以EHR为接口的 在护理点高效集成快速基因组医学的转换平台，使用NICU作为 一个实验室。目标一号将设计新的工具，以改进所有形式的基因变异的发现， 包括难以发现的复杂结构变体。这些新颖的工具将作为开源共享 软件，以及用于传播和实施的配套工具，以增强翻译基因组学 整个CTSA网络的科学。AIM 2将部署一个便携的EHR接口平台用于快速基因组 在整个EHR系统中适当、可接受和可行的诊断，并将催化临床和 地方、地区和国家的翻译科学。目标3将使用参与式规划战略，并 科学传播和实施的现状科学方法的发展、调整和运作 支持NICU采用、实施和可持续发展RAPID转换平台的战略 基因组诊断学。这些策略将被汇编成可推广的蓝图，以促进基因组 CTSA网络中的创新，并支持更广泛地采用和持续实施 基因组医学。

SUMMARY While the past decade has seen an explosion in basic genomic research, the clinical implementation of genomic medicine remains elusive. This Specialized Innovation Program (SIP) will identify and overcome barriers that impede the translational science of rapid genomic medicine discoveries at the point of care by assembling the infrastructure, technology, and strategies to design and develop a rapid genomic diagnostic platform, using the newborn intensive care unit (NICU) as a laboratory. Emerging clinical guidelines support the value and utility of rapid whole-genome sequencing in the NICU, yet multiple barriers impede the widespread use of this technology at the point of care. Specifically, (1) less than half of rare Mendelian diseases are solvable using current sequencing and analytical technologies; (2) industry electronic health record (EHR)-based genomic medicine applications are essentially nonexistent, with a lack of EHR-interfaced platforms that allow for visualization and team-based interpretation of genomic sequencing; (3) translational science strategies to implement genomic medicine into clinical care are currently lacking. To overcome these barriers, the SIP will design and develop an innovative, collaborative, patient-focused, and EHR-interfaced translational platform that efficiently integrates rapid genomic medicine at the point of care, using the NICU as a laboratory. Aim 1 will design novel tools that will improve the discovery of all forms of genetic variation, including difficult-to-detect complex structural variants. These novel tools will be shared as open-source software, with accompanying tools for dissemination and implementation, to empower translational genomic science across the CTSA network. Aim 2 will deploy a portable EHR-interfaced platform for rapid genomic diagnostics that is appropriate, acceptable, and feasible across EHR systems and will catalyze clinical and translational science locally, regionally, and nationally. Aim 3 will use a participatory planning strategy and state of the science dissemination and implementation science methods to develop, tailor, and operationalize strategies to support NICU adoption, implementation, and sustainability of a translational platform for rapid genomic diagnostics. These strategies will be compiled into a generalizable blueprint to foster genomic innovations across the CTSA network and empower broader adoption and sustained implementation of genomic medicine.