Integrating the Exposome into Longitudinal Multiomics Profiling

将暴露组整合到纵向多组学分析中

• 批准号: 9752623
• 负责人: Sophia Miryam Schüssler-Fiorenza Rose
• 金额: $ 21.16万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9752623
• 关键词: Acute; Address; Adipose tissue; Adverse effects; Affect; Age; American; Antibiotics; Award; Biological; Biological Assay; Blood; Blood Glucose; Body Weight; Body Weight decreased; Centers for Population Health; Certification; Chemical Exposure; Clinical; Complex; Cultural Evolution; Data; Data Analyses; Development; Diabetes Mellitus; Discipline; Disease; Doctor of Philosophy; Environmental Exposure; Environmental Pollution; Epidemic; Equipment and supply inventories; Ethnic group; Evolution; Exercise; Exposure to; Fiber; Genes; Goals; Grant; Health; Health Sciences; Human; Immune System Diseases; Impairment; Insulin Resistance; Interdisciplinary Study; Intervention; Joints; Laboratories; Lead; Learning; Life Experience; Life course epidemiology; Link; Lipids; Longevity; Mathematical Biology; Measures; Medicine; Mentors; Metabolic; Methods; Modeling; Molecular; Multiomic Data; Nervous System Trauma; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organic Chemicals; Outcome; Participant; Pathway interactions; Patients; Physical Medicine; Physical Rehabilitation; Physicians; Plasma; Polychlorinated Biphenyls; Precision Health; Property; Psychoneuroimmunology; Race; Recombinant DNA; Research; Risk; Role; Sampling; Scientist; Shapes; Source; Spectrometry; Spinal cord injury; Stress; Surveys; System; Systems Biology; Time; Toxicant exposure; Urine; Vaccination; Variant; Weight Gain; Work; analytical method; behavior measurement; blood glucose regulation; career; causal model; chemokine; cohort; cytokine; data warehouse; design; diabetes risk; diet and exercise; experience; exposed human population; gut microbiome; high risk; improved; innovation; ion mobility; learning algorithm; metabolome; microbiome; multiple omics; network models; novel; novel strategies; organochlorine pesticide; personalized medicine; polybrominated diphenyl ether; population based; population health; precision medicine; programs; psychosocial; racial and ethnic; resilience; skills; social genomics; societal costs; tool; transcriptome; transcriptome sequencing

PROJECT SUMMARY/ABSTRACT This is an application for a K08 award for Sophia Miryam Schüssler-Fiorenza Rose, MD, PhD, a Physical Medicine and Rehabilitation physician with subspecialty certification in Spinal Cord Injury Medicine and a Population Health Scientist. Her long-term goal is to lead a multidisciplinary research team that can apply complex systems approaches and other novel analytic methods to address the effects of adverse exposures on neurorecovery and long term health in those affected by neurotrauma and related diseases. This K08 award will provide Dr. Rose the support necessary to accomplish the following educational goals. 1. Develop expertise assessing the environmental, psychosocial and internal exposome. 2. Develop expertise in assessing biological effects of exposures using longitudinal multiomics profiling. 3. Develop advanced skills in longitudinal multiomics data analysis, complex systems and causal modeling approaches. 4. Develop skills in leading multidisciplinary research teams. 5. Develop translational skills and design a study to validate some of the findings of the research in a clinical or population based sample that will serve as a launching point for her independent research career. To achieve these goals, Dr. Rose has assembled a mentoring team comprised of the following experts: Dr. Michael Snyder (primary mentor) is a leader in the field of personalized medicine who has established a unique cohort undergoing comprehensive, state-of-the-art, multiomics profiling with frequent longitudinal sampling. He provides access to this rich data repository as well as laboratory support for novel analyses. Dr. Mark Cullen is director of the Stanford Center for Population Health Sciences and leader of Stanford Precision Health for Ethnic and Racial Equity Center which focuses on using precision-medicine tools to improve the health of underserved ethnic and racial groups. Dr. Cullen brings considerable experience in integrating data on toxic exposures, psychosocial exposures and behavioral measures to understand how different aspects of the exposome act in combination to produce positive and negative outcomes. Dr. David Rehkopf is an expert in life course epidemiology and advanced longitudinal, nonlinear and spatial data analysis methods. Dr. Marc Feldman is an expert in complex systems and mathematical biology whose work in quantitative cultural evolution combines tools from multiple disciplines to understand the combined roles of culture and genes in shaping human evolution. Dr. George Slavich is an expert in stress assessment, social genomics and psychoneuroimmunology. The specific aims are as follows: Aim 1. Add a targeted assay for persistent organic chemicals (POCs) as a measure of POC exposure to the study and characterize relationship to the internal exposome, adversity and stress exposures. Aim 2. Evaluate the longitudinal trajectories of POCs and their covariation with clinical and omics measures. Aim 3. Integrate longitudinal multiomics data and multiple perturbation data to create a Complex Systems - Causal Network model to evaluate the joint effects of POCs and other exposures on impaired glucose regulation.

项目概要/摘要 这是索菲亚·米里亚姆·舒斯勒-菲奥伦扎·罗斯 (Sophia Miryam Schüssler-Fiorenza Rose) 的 K08 奖项申请，她是医学博士、哲学博士、物理医学和 拥有脊髓损伤医学亚专业认证的康复医师和人口健康科学家。 她的长期目标是领导一个多学科研究团队，能够应用复杂的系统方法和其他新颖的方法 解决不良暴​​露对神经恢复和长期健康影响的分析方法 神经外伤及相关疾病。 该 K08 奖项将为 Rose 博士提供实现以下教育目标所需的支持。 1. 发展评估环境、社会心理和内部暴露的专业知识。 2. 培养评估方面的专业知识 使用纵向多组学分析来确定暴露的生物效应。 3. 发展纵向高级技能 多组学数据分析、复杂系统和因果建模方法。 4. 培养领导多学科的技能 研究团队。 5. 培养转化技能并设计一项研究以验证临床研究的一些结果 或基于人口的样本，这将作为她独立研究生涯的起点。 为了实现这些目标，罗斯博士组建了一个由以下专家组成的指导团队：迈克尔·斯奈德博士 （主要导师）是个性化医疗领域的领导者，他建立了一个独特的队列，正在进行 通过频繁的纵向采样进行全面、最先进的多组学分析。他提供了接触这位富人的机会 数据存储库以及对新颖分析的实验室支持。马克·卡伦博士是斯坦福大学研究中心主任 人口健康科学和斯坦福精准健康民族和种族平等中心的领导者，该中心专注于 使用精准医疗工具改善服务不足的民族和种族群体的健康。卡伦博士带来了相当多的 整合有毒物质暴露、心理社会暴露和行为测量数据的经验，以了解如何 暴露体的不同方面结合起来会产生积极和消极的结果。大卫·雷科普夫 (David Rehkopf) 博士是 生命历程流行病学和先进的纵向、非线性和空间数据分析方法专家。马克博士 费尔德曼是复杂系统和数学生物学方面的专家，他在定量文化进化方面的工作结合了 来自多个学科的工具来了解文化和基因在塑造人类进化中的综合作用。博士。 乔治·斯拉维奇（George Slavich）是压力评估、社会基因组学和心理神经免疫学方面的专家。 具体目标如下： 目标 1. 增加持久性有机化学品 (POC) 的靶向测定作为 POC 的衡量标准 暴露于研究并表征与内部暴露、逆境和压力暴露的关系。目标 2. 评估 POC 的纵向轨迹及其与临床和组学测量的协变。目标 3. 纵向整合 多组学数据和多重扰动数据创建复杂系统 - 因果网络模型来评估联合 POC 和其他暴露对葡萄糖调节受损的影响。