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

未确诊疾病网络 (UDN) III 期 BCM 临床站点 (U01)

• 批准号: 10696573
• 负责人: Carlos A. Bacino
• 金额: $ 62.8万
• 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 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696573
• 关键词: Acceleration; Adult; Area; Basic Science; Biochemical; Biological; Biology; Bone Diseases; Candidate Disease Gene; Cardiovascular system; Caring; Cellular biology; Centers of Research Excellence; Childhood; Clinic; Clinical; Clinical Investigator; Clinical Pathology; Clinical Research; Clinical Treatment; Clinical Trials; 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; Funding; Genetic; Genetic Medicine; Genomic medicine; Genomics; Genotype; Goals; Human Genetics; Hybrids; Infrastructure; Institute of Medicine (U.S.); Institution; Internal Medicine; Joint Ventures; Knockout Mice; Laboratories; Lead; Leadership; Medical Genetics; Medical center; Medicine; Mitochondria; Modeling; Molecular; Molecular Analysis; Molecular Diagnosis; Molecular Genetics; National Center for Advancing Translational Sciences; National Human Genome Research Institute; Neurologic; Neurology; Online Systems; Organ; Organization administrative structures; Pathway interactions; Patient Care; Patients; Pediatric Hospitals; Pediatrics; Persons; Phase; Phenotype; Population; Program Sustainability; Protocols documentation; Provider; Rare Diseases; Research; Research Activity; Research Infrastructure; Research Institute; Research Personnel; Research Support; Scientist; Services; Site; Specialized Center; Standardization; Texas; Time; Transfer RNA; Translating; Translational Research; Translations; Underinsured; Underrepresented Populations; Underserved Population; United States National Institutes of Health; Variant; Whole Blood; bioinformatics pipeline; care delivery; clinical care; clinical diagnostics; clinical research site; clinical training; college; community engagement; cost; disease diagnosis; disease mechanisms study; exome sequencing; experience; gene discovery; genetic variant; genome sequencing; genomic data; human genome sequencing; implementation strategy; improved; innovation; innovative technologies; molecular pathology; neurogenetics; payment; pediatric department; phase 2 testing; precision medicine; prenatal; programs; recruit; research clinical testing; research study; service delivery; skeletal; standard of care; technological innovation; tool; transcriptome sequencing; virtual; virtual platform; Acceleration; Adult; Area; Basic Science; Biochemical; Biological; Biology; Bone Diseases; Candidate Disease Gene; Cardiovascular system; Caring; Cellular biology; Centers of Research Excellence; Childhood; Clinic; Clinical; Clinical Investigator; Clinical Pathology; Clinical Research; Clinical Treatment; Clinical Trials; 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; Funding; Genetic; Genetic Medicine; Genomic medicine; Genomics; Genotype; Goals; Human Genetics; Hybrids; Infrastructure; Institute of Medicine (U.S.); Institution; Internal Medicine; Joint Ventures; Knockout Mice; Laboratories; Lead; Leadership; Medical Genetics; Medical center; Medicine; Mitochondria; Modeling; Molecular; Molecular Analysis; Molecular Diagnosis; Molecular Genetics; National Center for Advancing Translational Sciences; National Human Genome Research Institute; Neurologic; Neurology; Online Systems; Organ; Organization administrative structures; Pathway interactions; Patient Care; Patients; Pediatric Hospitals; Pediatrics; Persons; Phase; Phenotype; Population; Program Sustainability; Protocols documentation; Provider; Rare Diseases; Research; Research Activity; Research Infrastructure; Research Institute; Research Personnel; Research Support; Scientist; Services; Site; Specialized Center; Standardization; Texas; Time; Transfer RNA; Translating; Translational Research; Translations; Underinsured; Underrepresented Populations; Underserved Population; United States National Institutes of Health; Variant; Whole Blood; bioinformatics pipeline; care delivery; clinical care; clinical diagnostics; clinical research site; clinical training; college; community engagement; cost; disease diagnosis; disease mechanisms study; exome sequencing; experience; gene discovery; genetic variant; genome sequencing; genomic data; human genome sequencing; implementation strategy; improved; innovation; innovative technologies; molecular pathology; neurogenetics; payment; pediatric department; phase 2 testing; precision medicine; prenatal; programs; recruit; research clinical testing; research study; service delivery; skeletal; standard of care; technological innovation; tool; transcriptome sequencing; virtual; virtual platform

Project Summary The Baylor College of Medicine (BCM) Undiagnosed Diseases Network (UDN) Clinical Site (CS) has successfully advanced the objectives of phase I and II 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 four sites to achieve 100% for completed phase II evaluations. We developed innovative approaches including RNA sequencing-directed analyses that led us to achieve a diagnostic rate for solved and strong candidate genes in 51% 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 and II of the BCM UDN CS. In phase III 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 and Baylor Genetics laboratory) and BCM UDN CS-specific bioinformatics pipelines. The interpretation and ultimate functional study of genomic data will flow to specialized organ-based research centers of excellence including NIH programs including KOMP and CPMM. For sustainability, BCM has 1) established and financially support a Center for Undiagnosed Diseases that leverage 3rd party payor support for standard of care, philanthropy for research studies, and institutional support, 2) leveraged a DMHG-developed 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 and low cost WGS and deep RNAseq with Ultima Genomics, 4) focus on engagement and recruitment of underserved and underinsured populations leveraging existing NIH funded projects within the DMHG (NHGRI Texome and NCATS Project GIVE), 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）成功地推进了第一阶段和II期UDN的目标。我们为未诊断疾病（UDD）患者建立了高通量的综合管道，以获取最新的诊断，临床和分子评估。我们在患者接受和亲自评估中领导了校外UDN临床部位，同时是完成II期评估的四个站点之一。我们开发了包括RNA测序指导分析的创新方法，使我们在51％迄今已完成的病例中实现了解决方案和强大候选基因的诊断率。最后，我们聘请了UDN和更广泛的科学/外行社区，共享最佳实践，协作发现和教育。这是通过利用BCM分子和人类遗传学（DMHG）的综合遗传和基因组计划来实现的。该部门是基础科学，临床和分子病理部门的结合。因为这些是在一个组织部门下消耗的，所以我们迅速将发现转化为实践，并在BCM，德克萨斯州医疗中心和全国范围内担任研究界的联系。 BCM遗传和基因组医学中DMHG的领导确保了将儿科，内科和神经病学的伙伴部门整合到BCM UDN CS的I和II期。在第三阶段，我们建议采用这种综合方法来实现UDN的新目标。 BCM UDN CS领导层包括遗传学，儿科，医学和神经病学领域的临床研究人员，他们将在范围内伙伴部门的顾问中吸引顾问时领导一支小组。临床描述和随后的DNA分子诊断将利用已建立的（人类基因组测序中心和贝勒遗传学实验室）和BCM UDN CS特异性生物信息学管道。基因组数据的解释和最终功能研究将流向基于专门的器官的卓越研究中心，包括NIH计划，包括KOMP和CPMM。为了可持续性，BCM有1）建立并在财务上支持一个未诊断的疾病中心，该中心利用第三方薪酬者支持用于护理标准，研究研究和机构支持，2）利用DMHG开发的虚拟虚拟平台用于医疗遗传学服务平台（Consultagene.org），并降低了临床范围，并降低了临床范围，并降低了临床的访问，并扩大了范围的访问，并扩大了范围的范围，并将其供应范围扩大，并降低了效率，并将其访问范围扩大，并降低了效率，并将其访问范围扩大。诊断竞技场，即贝勒遗传学实验室和低成本WGS以及具有Ultima基因组学的深层RNASEQ，4）专注于对贫乏和保险人群的参与和招聘，利用了DMHG中现有的NIH资助项目，而NHGRI和NCATS Project中的NHGRI和NCATS Project中的NIH资助项目（5）进行了施加较高的研究。