BCM Clinical Site for an Undiagnosed Disease Network (UDN) Phase II (U01)

未确诊疾病网络 (UDN) II 期 BCM 临床站点 (U01)

• 批准号: 9789928
• 负责人: Carlos A. Bacino
• 金额: $ 150万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789928
• 关键词: Adult; Animal Model; Area; Basic Science; Biochemical; Bioinformatics; Biological; Biology; Bone Diseases; Candidate Disease Gene; Cardiovascular system; Caring; Cellular biology; Central America; Childhood; Clinic; Clinical; Clinical Investigator; Clinical Medicine; Clinical Pathology; Clinical Research; Clinical Treatment; Collaborations; Communities; Complement; Consumption; DNA; Data; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Education; Educational process of instructing; Ensure; Environmental Exposure; Etiology; Evaluation; Extramural Activities; Faculty; Financial Support; Functional disorder; Future; Gap Junctions; Genetic; Genetic Medicine; Genomic medicine; Genomics; Genotype; Goals; Human; Human Genetics; Immunology; Infrastructure; Institute of Medicine (U.S.); Institution; Internal Medicine; International; Joint Ventures; Jordan; Knockout Mice; Laboratories; Lead; Leadership; Medical Genetics; Medical Research; Medical center; Medicine; Mitochondria; Modeling; Molecular; Molecular Analysis; Molecular Diagnosis; Molecular Genetics; Neurologic; Neurology; Online Systems; Oranges; Organ; Organization administrative structures; Pathway interactions; Patient Care; Patients; Pediatric Hospitals; Pediatric Neurology; Pediatrics; Persons; Phase; Phenotype; Program Sustainability; Protocols documentation; Provider; Rare Diseases; Research; Research Activity; Research Infrastructure; Research Institute; Research Personnel; Resources; Scientist; Services; Site; South America; Southwestern United States; Specialized Center; Standardization; Technology; Texas; Time; Training; Transfer RNA; Translating; Translational Research; Translations; United States National Institutes of Health; Variant; Whole Blood; base; care delivery; clinical care; clinical diagnostics; clinical research site; college; cost; disease diagnosis; disease mechanisms study; exome sequencing; experience; gene discovery; genetic variant; genome sequencing; genomic data; gulf coast; health economics; human genome sequencing; implementation strategy; improved; innovation; innovative technologies; molecular pathology; network models; neurogenetics; payment; pediatric department; prenatal; programs; research clinical testing; screening; service delivery; skeletal; tool; transcriptome sequencing; treatment trial; virtual

Project Summary The Baylor College of Medicine (BCM) Undiagnosed Diseases Network (UDN) Clinical Site (CS) has successfully advanced the objectives of phase I UDN. We established a high throughput integrated pipeline for patients with undiagnosed diseases (UDD) to access a state of the art diagnostic, clinical, and molecular evaluation. We led extramural UDN clinical sites in number of patient acceptances and in person evaluations, while being one of two extramural sites to achieve 100% for these two key milestones. We developed innovative approaches including trio RNA sequencing that led us to achieve a diagnostic rate for solved and strong candidate genes in 45% of cases completed to date. Finally, we engaged the UDN and the broader scientific/lay community in sharing best practices, collaborative discovery, and education. This was achieved by leveraging the integrated genetic and genomic program that is the Department of Molecular and Human Genetics (DMHG) at BCM. The Department is a combination of basic science, clinical, and molecular pathology departments. Because these are consumed under one organizational unit, we have rapidly translated discovery to practice, and served as a nexus for the research community at BCM, the Texas Medical Center, and nationally. The leadership of the DMHG in genetic and genomic medicine at BCM has ensured the integration of the partnering Departments of Pediatrics, Internal Medicine, and Neurology into phase I of the BCM UDN CS. In phase II we propose to apply this integrated approach to achieve the new and ongoing objectives of the UDN. The BCM UDN CS leadership includes established clinical investigators in Genetics, Pediatrics, Medicine, and Neurology who will lead a primary team while drawing from consultants in partner Departments institution-wide. Clinical delineation and subsequent DNA molecular diagnosis will leverage both established (Human Genome Sequencing Center, Baylor Genetics laboratory, and NIH Center for Mendelian Genomics) and BCM UDN CS-specific bioinformatics pipelines. The interpretation and ultimate functional study of genomic data will flow to specialized organ-based research centers including the Center for Skeletal Medicine and Biology (led by Dr. Brendan Lee), the Neurological Research Institute (led by Dr. Huda Zoghbi), the Center for Human Immunology (led by Dr. Jordan Orange), and the NIH UDN Model Organism Screening Center and Knockout Mouse Phenotyping programs. For sustainability, BCM will 1) establish and financially support a Center for Undiagnosed Diseases, 2) leverage a newly developed DMHG virtual platform for medical genetics care delivery platform (Consultagene.org) to increase efficiency, decrease cost, and expand access for patient and provider engagement, 3) translate research tools to the clinical diagnostic arena, i.e., Baylor Genetics laboratory, 4) complete ongoing health economic studies to improve payor coverage for these tools, and 5) widely disseminate patient variants to stimulate collaboration with basic scientists for functional studies.

项目摘要 贝勒医学院（BCM）未诊断的疾病网络（UDN）临床部位（CS） 成功提出了I阶段UDN的目标。我们建立了高通量的集成管道 对于未诊断疾病（UDD）的患者，可以进入最先进的诊断，临床和分子的状态 评估。我们在患者接受和人身评估中领导了壁外UDN临床部位 而这是两个关键里程碑100％实现100％的壁外场所之一。我们开发了 创新方法，包括三个RNA测序，使我们实现了解决的诊断率和 迄今为止，有45％的案例中有45％的候选基因。最后，我们参与了UDN，更广泛 科学/外行社区共享最佳实践，协作发现和教育。这是实现的 通过利用分子和人类部的综合遗传和基因组计划 BCM的遗传学（DMHG）。该部是基础科学，临床和分子的结合 病理部门。因为这些是在一个组织单位下消费的，所以我们迅速 将发现翻译成实践，并在德克萨斯州医学BCM的研究社区担任联系 中心和全国。 BCM遗传和基因组医学中DMHG的领导已确保 儿科，内科和神经病学的伙伴部门整合到I期 BCM UDN CS。在第二阶段，我们建议采用这种综合方法来实现新的和持续的 UDN的目标。 BCM UDN CS领导层包括识别遗传学的临床研究者， 儿科，医学和神经病学，他们将在合作伙伴的顾问吸引顾问时领导一支小组 部门范围内。临床描述和随后的DNA分子诊断将利用 已建立（人类基因组测序中心，贝勒遗传学实验室和NIH孟德尔中心 基因组学）和BCM UDN CS特异性生物信息学管道。解释和最终功能 基因组数据的研究将流向包括骨骼骨骼中心在内的专门基于器官的研究中心 医学与生物学（由Brendan Lee博士领导），神经学研究所（由Huda Zoghbi博士领导）， 人类免疫学中心（由乔丹·奥兰治（Jordan Orange）博士领导）和NIH UDN模型有机体筛查 中心和淘汰鼠标表型程序。对于可持续性，BCM将1）建立和财务 支持一个未诊断疾病的中心，2）利用新开发的DMHG虚拟平台用于医疗 遗传学护理输送平台（Consuregene.org）提高效率，降低成本并扩大访问权限 对于患者和提供者的参与，3）将研究工具转换为临床诊断领域，即贝勒 遗传学实验室，4）完成正在进行的健康经济研究以改善这些工具的付款人覆盖范围， 5）广泛传播患者变体，以刺激与基本科学家进行功能研究的合作。