Intermountain West Clinical Site for the Undiagnosed Disease Network (UDN), Phase 2

项目摘要/摘要 我们建议在犹他大学建立一个山间西部临床站点，供未确诊的患者使用 疾病网络。拟建的选址将提供前所未有的通道，进入横跨五个州的广阔区域 约占美国大陆的10%。它的居民是美国最缺乏服务的人之一； 农村、少数民族和低收入群体历来“从基因上看得不到充分的服务”，包括一大批土著 美国人口。为了推进最先进的诊断和管理，我们将利用我们成功的 儿科佩内洛普计划--我们的创新实验室和概念验证计划，针对未确诊和 罕见疾病--进一步开发和测试用于临床评估和护理的流程、方案和工具 所有年龄段都患有未确诊疾病的人。与临床项目紧密相连，我们的生物信息学 团队将为UDN带来创新的生物信息学工具，以提高基因组的能力和覆盖范围 发现号。我们的国际公认的团队已经开发出将测序数据与临床相结合的工具 和系谱信息(VAAST，Gemini，Rufus)，以更好地寻找致病变异。重要的是，一些 这些工具(IOBIO)是为没有广泛生物信息学背景的临床医生设计的，以加快 加快并扩大最先进的基因检测的范围，超越学术中心，进入 社区。为了提高可持续性，我们将改进和共享我们计划的工具和护理流程模型 有效地整合临床和研究工作流程。 总而言之，西山间临床站点将带来团队、经验、资源和机构 支持推进UDN的共同目标-改善疑难诊断的诊断和管理 和新的疾病--高效、公平和可持续。

PROJECT SUMMARY/ABSTRACT We propose to establish an Intermountain West Clinical Site at the University of Utah for the Undiagnosed Disease Network. The proposed site will provide unprecedented access to a vast area across five states that encompasses ~10% of the Continental US. Its residents are among the most underserved in the United States; with rural, minority, and low-income groups historically `genetically underserved', including a large Native American population. To advance state-of-the-art diagnosis and management, we will leverage our successful pediatric Penelope program—our `innovation laboratory' and proof-of concept program for undiagnosed and rare diseases--to further develop and test processes, protocols, and tools for clinical assessment and care of people with undiagnosed diseases of all ages. Integrally connected to the clinical program, our bioinformatics team will bring to the UDN innovative bioinformatics tools to advance the power and the reach of genomic discovery. Our internationally recognized team has developed tools that integrate sequencing data with clinical and pedigree information (VAAST, GEMINI, RUFUS) to better find disease-causing variants. Importantly, some of these tools (IOBIO) are designed for clinicians without extensive bioinformatics background, to quicken the pace and expand the reach of state-of-the-art genetic testing beyond academic centers and into the community. To improve sustainability, we will refine and share our program's tools and care process models that integrate clinical and research workflows efficiently. In summary, the Intermountain West Clinical Site will bring the team, experience, resources, and institutional support to advance the shared goal of UDN – improve the diagnosis and management of difficult-to-diagnose and new diseases—efficiently, equitably, and sustainably.