Vanderbilt Integrated Center of Excellence in Maternal and Pediatric Precision Therapeutics (VICE-MPRINT)

项目摘要/摘要--总体 有一个迅速扩大的知识库，使许多人类疾病的精确治疗成为可能， 但在证据生成方面仍有大量未得到满足的需求，以支持儿童治疗的转化 以及怀孕/产后妇女。最近广泛采用电子健康记录(EHR)和 这些数据与其他大型数据集的关联为临床研究带来了前所未有的机遇 和发现力。这个妇幼精准治疗卓越中心的目标是： 解决关键知识差距并进行药物基因组学和新生儿阿片类药物的临床研究 戒断综合症；利用数据科学方法并开发支持孕产妇的新工具 和儿科精准治疗研究；以及加强母儿精准培训 地方、地区和国家层面的治疗。我们为这项工作带来了独特的 调查人员、机构支持、工具和资源，使范式从当前的规范转变为 缓慢、渐进的进展。项目1将：使用社区参与的方法来说明知识， 对药物基因组学的态度和优先事项；验证母体的药物基因组学关联 使用创新的和可推广的EHR表型策略；并确定和 量化不同个体中具有未知功能后果的变异，为未来的研究工作提供信息 并缩小差距。项目2将：开发和验证基于EHR的算法，以识别一组阿片类药物- 暴露的婴儿和他们的母亲(二联体)，并创建这些数据与全州数据的新联系； 假设使用药物治疗阿片类药物使用障碍与改善早期结果有关；以及 测试阿片类药物使用障碍治疗与新发现的改善相关的假设 二元稳定性的纵向结果。这些项目由多学科团队领导，包括 儿科学和产科的研究人员，在各自领域是国家公认的领导者。 这两个项目都将得到一个科学核心--表型支持核心--的支持，该核心将加强每个项目 具有专家表型、机器学习/人工智能以及推广和应用经验的项目 传播表型鉴定方法。行政核心将为中心提供后勤支持， 监督培训机会，并确保在CET内部以及与MPRINT中心进行科学交流。 这项工作将有助于为母亲和儿童提供精确治疗的创新方法，并将 发展教育基础设施以支持内科科学家的培训，以支持进一步的进步 很好地进入未来。

PROJECT SUMMARY / ABSTRACT - OVERALL There is a rapidly expanding knowledge base enabling precision therapeutics for a number of human diseases, but there are significant unmet needs in evidence generation to support translation to the treatment of children and pregnant/post-partum women. The recent widespread adoption of electronic health records (EHRs) and the linkage of these data to other large datasets represents an unprecedented opportunity for clinical research and discovery. The goals of this Center of Excellence in Maternal and Pediatric Precision Therapeutics are: to address key knowledge gaps and perform clinical research in pharmacogenomics and neonatal opioid withdrawal syndrome; to leverage data science methodologies and develop novel tools that support maternal and pediatric precision therapeutics research; and to enhance training for maternal and pediatric precision therapeutics at the local, regional, and national levels. We bring to this effort a unique collection of investigators, institutional support, tools, and resources that enable a paradigm-shift from current norms of slow, incremental progress. Project 1 will: use a community engaged approach to illuminate knowledge of, attitudes about, and priorities for pharmacogenomics; validate pharmacogenomic associations for maternal and pediatric populations using the innovative and generalizable strategy of EHR phenotyping; and identify and quantify variants with unknown functional consequence in diverse individuals to inform future research efforts and reduce disparities. Project 2 will: develop and validate EHR-based algorithms to identify a cohort of opioid- exposed infants and their mothers (dyads) and create a novel linkage of these data to state-wide data; test the hypothesis that use of medications for opioid use disorder is associated with improved early outcomes; and test the hypothesis that opioid use disorder treatment is associated with improvements in the novel longitudinal outcome of dyadic stability. These projects are led by multidisciplinary teams that include Investigators in Pediatrics and Obstetrics, and who are nationally recognized leaders in their respective fields. Both Projects will be supported by a Scientific Core – the Phenotyping Support Core - which enhances each project with expert phenotyping, machine learning/artificial intelligence, and experience in generalizing and disseminating phenotyping approaches. An Administrative Core will provide logistical support for the Center, supervise training opportunities, and ensure scientific interchange within the CET and with the MPRINT Hub. This work will contribute to innovative approaches to precision therapeutics for mothers and children and will develop the educational infrastructure to support the training of physician-scientists to support further advances well into the future.