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

项目概要/摘要 我们建议在犹他州大学建立一个山间西部临床基地， 疾病网络拟议中的网站将提供前所未有的进入五个州的广阔地区， 涵盖美国大陆约10%的地区。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在历史上“遗传不足”，包括一个大的土著人， 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Penelope计划-我们的“创新实验室”和概念验证计划，用于未确诊和 罕见疾病-进一步开发和测试临床评估和护理的流程，协议和工具， 所有年龄段的未确诊疾病患者。与临床项目紧密相连，我们的生物信息学 该团队将为UDN带来创新的生物信息学工具，以提高基因组学的能力和影响力。 的发现我们国际公认的团队开发了将测序数据与临床 和系谱信息（VAAST、GEMINI、RUFUS），以更好地发现致病变异。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， 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，我们将完善和分享我们的计划的工具和护理流程模型 有效整合临床和研究工作流程。 综上所述，Intermountain West临床中心将带来团队、经验、资源和机构 支持推进UDN的共同目标-改善难以诊断的疾病的诊断和管理 和新的疾病--高效、公平和可持续地。

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.