Intermountain West Clinical Center for a Childhood Liver Disease Research Network

西山间儿童肝病研究网络临床中心

• 批准号: 10414925
• 负责人: Stephen L Guthery
• 金额: $ 57.52万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-20 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10414925
• 关键词: Academy; Adolescent; Age; American; Biliary Atresia; Bilirubin; Biochemistry; Bioinformatics; Biological; Biology; Birth; Caring; Child; Childhood; Clinical Data; Complex; Comprehensive Health Care; Computers; DNA Sequence; Data; Data Collection; Diagnosis; Diagnostic; Disease; Enrollment; Etiology; Feasibility Studies; Funding; Future; Genetic; Genetic Predisposition to Disease; Genome; Genomic approach; Genomic medicine; Genomics; Goals; Health; Healthcare; Healthcare Systems; Hepatology; Hospitals; Infant; Infrastructure; Integrated Health Care Systems; Knowledge; Liver diseases; Measures; Molecular Diagnosis; Morbidity - disease rate; Mothers; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Neonatal Screening; Newborn Infant; Online Systems; Parents; Participant; Pathologist; Pathology; Patients; Pediatric Hospitals; Pediatric Radiology; Pediatric Surgical Procedures; Pediatrics; Phenotype; Physiology; Pilot Projects; Process; Progressive intrahepatic cholestasis; Protocols documentation; Public Health; Rare Diseases; Research; Research Design; Research Personnel; Serum; Shipping; Site; Software Tools; Source; Specimen; Surgeon; Syndrome; Testing; Time; U-Series Cooperative Agreements; United States National Institutes of Health; Universities; Utah; alpha 1-Antitrypsin Deficiency; analysis pipeline; base; case control; clinical center; cost effective; data dissemination; design; disease-causing mutation; exome; exome sequencing; experience; feasibility testing; genome analysis; genome sequencing; improved; improved outcome; liver transplantation; malformation; mortality; multidisciplinary; novel therapeutics; performance site; post-transplant; radiologist; retention rate; screening; screening program; standard of care; terabyte; tool; total measurement Bilirubin; web-based tool; whole genome

PROJECT SUMMARY ABSTRACT Our goal is to continue the Intermountain West Clinical Center for the Childhood Liver Disease Research Network (ChiLDReN) at the University of Utah and Primary Children's Hospital. During the previous funding cycle, we enrolled and retained a significant number of participants, achieved outstanding site performance, and participated in a highly collaborative manner in all Network activities. Additionally, during the previous funding cycle, we transferred, aligned, and processed DNA sequences in support of all Network genomics efforts, and provided the infrastructure to share these sequence data with Network investigators via web- based, password protected software tools. In Aim 1, we will continue to enroll infants, children, and adolescents in current and future ChiLDReN protocols, continue to submit valuable biological specimens and accurate and timely data, and collaboratively participate in all Network activities. In Aim 2, we propose to test the feasibility of a biliary atresia newborn screening program in a large integrated healthcare system covering ~30,000 deliveries per year. All newborns in this healthcare system already undergo total serum bilirubin screening as part of standard of care. We will embed a pilot study in Aim 2 to measure the impact on mothers of newborns with a false positive newborn screen using a case-control repeated measures study design. In Aim 3, we will perform whole genome sequencing on 10 participants and their parents in whom exome sequencing failed to identify a molecular diagnosis. For this Aim, Network investigators will collaboratively select subjects for whole genome sequencing using University of Utah-developed web-based tools. These tools require no bioinformatic expertise and enable expert, Network-wide central genome review. Accomplishing the proposed aims as a highly collaborative Center for ChiLDReN will lead to new knowledge regarding the biochemistry, physiology, and mechanisms of childhood liver diseases, and improve the diagnostic and management options for children afflicted with them.

项目总结摘要 我们的目标是继续山间西部儿童肝病研究临床中心 犹他州大学和小学儿童医院的儿童网络。在之前的资助期间 周期，我们招募并保留了相当数量的参与者，取得了出色的现场表现， 并以高度协作的方式参与了网络的所有活动。此外，在之前的 资金周期，我们转移、比对和处理DNA序列以支持所有网络基因组学 并提供了通过网络与网络调查人员共享这些序列数据的基础设施- 基于密码保护的软件工具。在目标1中，我们将继续招收婴儿、儿童和 在当前和未来的儿童议定书中，青少年继续提交有价值的生物标本和 准确、及时的数据，并协作参与所有网络活动。在目标2中，我们建议测试 大型综合医疗系统中胆道闭锁新生儿筛查计划的可行性 每年约30,000次送货。这个医疗保健系统中的所有新生儿都已经接受了血清总胆红素 筛查是护理标准的一部分。我们将在目标2中嵌入一项试点研究，以衡量对母亲的影响 采用病例对照重复测量研究设计，对假阳性新生儿进行筛查。在……里面 目的3，我们将对10名参与者及其父母进行全基因组测序 测序未能确定分子诊断。为此，网络调查人员将合作 使用犹他大学开发的基于网络的工具选择用于全基因组测序的对象。这些 工具不需要生物信息学专业知识，并支持专家、网络范围的中央基因组审查。 作为一个高度合作的儿童中心，实现拟议的目标将带来新的知识 关于儿童肝病的生化、生理和机制，并改善 为患有这些疾病的儿童提供诊断和管理选择。