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

项目总结/摘要-总体 有一个迅速扩大的知识基础，使精确治疗许多人类疾病， 但在证据生成方面仍有大量未满足的需求， 和孕妇/产后妇女。最近广泛采用电子健康记录（EHR）， 这些数据与其他大型数据集的链接为临床研究带来了前所未有的机会 和发现该中心在孕产妇和儿科精准治疗卓越的目标是： 解决关键的知识差距，并在药物基因组学和新生儿阿片类药物方面开展临床研究 戒断综合征;利用数据科学方法，开发新的工具， 和儿科精确治疗研究;并加强孕产妇和儿科精确治疗的培训 在地方、区域和国家层面的治疗。我们为这项工作带来了一个独特的收集， 调查人员，机构支持，工具和资源，使范式转变，从目前的规范， 缓慢而渐进的进步。项目1将：使用社区参与的方法来阐明知识， 对药物基因组学的态度和优先事项;验证药物基因组学与孕产妇 和儿科人群使用EHR表型的创新和推广策略;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 减少差距。项目2将：开发和验证基于EHR的算法，以识别阿片类药物队列- 暴露的婴儿和他们的母亲（二人组），并创建一个新的链接，这些数据的国家范围内的数据;测试 假设使用阿片类药物使用障碍的药物与改善的早期结果相关;以及 检验阿片类药物使用障碍治疗与小说中的改善相关的假设。 二进稳定性的纵向结果。这些项目由多学科团队领导，包括 儿科和产科的研究人员，他们是各自领域的国家公认的领导者。 这两个项目都将得到一个科学核心的支持-表型支持核心-这提高了每个 项目与专家表型，机器学习/人工智能，并在推广和 传播表型分析方法。一个行政核心将为中心提供后勤支助， 监督培训机会，并确保CET内部以及与MPRINT Hub的科学交流。 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， 发展教育基础设施，以支持对医生和科学家的培训，支持进一步的进步 在未来很久。

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.