Intermountain West Clinical Center for a Childhood Liver Disease Research Network

项目概要 摘要 我们的目标是继续开展西山间儿童肝脏疾病研究临床中心 犹他大学和初级儿童医院的网络 (ChiLDReN)。在上一次融资期间 周期中，我们招募并保留了大量参与者，取得了出色的现场表现， 并以高度协作的方式参与所有网络活动。另外，在之前的 资金周期中，我们转移、比对和处理 DNA 序列以支持所有网络基因组学 努力，并提供基础设施以通过网络与网络调查人员共享这些序列数据 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 当前和未来 ChiLDReN 协议中的青少年，继续提交有价值的生物样本和 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 大型综合医疗保健系统中胆道闭锁新生儿筛查计划的可行性 每年约 30,000 次交货。该医疗保健系统中的所有新生儿均已接受血清总胆红素检测 筛查作为标准护理的一部分。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 使用病例对照重复测量研究设计对新生儿筛查假阳性的新生儿进行评估。在 目标3，我们将对10名参与者及其父母进行全基因组测序，其中外显子组 测序未能确定分子诊断。为了实现这一目标，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进行全基因组测序的受试者。这些 工具不需要生物信息专业知识，并支持专家、网络范围的中央基因组审查。 实现作为高度协作的儿童中心的拟议目标将带来新知识 关于儿童肝脏疾病的生物化学、生理学和机制，并提高 为患有这些疾病的儿童提供诊断和管理方案。

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.