Genomic Translation Across Species Core

跨物种基因组翻译核心

基本信息

批准号：
10044924
负责人：
EILEEN M CRIMMINS
金额：
$ 5.95万
依托单位：
BUCK INSTITUTE FOR RESEARCH ON AGING
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10044924
关键词：
Activities of Daily Living Adult Age Aging Animal Model Back Behavioral Bioinformatics Biological Biological Markers Biological Models Biological Process Blood California Cardiovascular Diseases Cognition Cognitive Communities Custom DNA Data Development Disease Disease Marker Emotional Environment Epigenetic Process Ethnic Origin Experimental Designs Gender Gene Expression Genes Genetic Genetic Transcription Genomics Genotype Geroscience Goals Health and Retirement Study Heterogeneity Homeostasis Human Immune Impaired cognition Individual Inflammaging Institutes Intervention Investments Linkage Disequilibrium Longevity Longitudinal Studies Measures Metabolism Methods Methylation Mission Outcome Participant Pathologic Phenotype Physiological Population Process Race Research Research Personnel Research Project Grants Resources Role Route Sampling Scanning Services Shock Subgroup Therapeutic Time Translational Research Translations Universities Validation Variant Vitamin Deficiency Work age related aged base behavioral phenotyping biodemography blood-based biomarker cardiovascular risk factor cognitive function cohort data warehouse density design epigenomics ethnic diversity experimental study follow-up frailty genomic biomarker genomic data healthspan high dimensionality human data indexing innovation insight interdisciplinary collaboration interest mortality normal aging novel phenome racial diversity resilience sex social telomere tool transcriptomics

项目摘要

ABSTRACT- Genomic Translation Across Species Core The overarching goal of the Genomic Translation Across Species Core (GTASC) aligns with the larger mission of the Nathan Shock Center, to advance translational research on biological processes contributing to aging- related outcomes through interdisciplinary collaboration. While there has been much progress in using model systems to understand biological processes underlying aging phenotypes related to healthspan and disease, the translation of findings in model organisms from biologists to clinicians in order to validate genetic, transcriptomic, or epigenetic associations with age-specific indicators in humans occurs very slowly, as does bringing findings back to model systems for experimental manipulation. The GTASC has a unique set of resources and expertise with which to facilitate translational processes in normal aging samples, with diversity in sex/gender and race/ethnic composition, and with age ranges from 50 to 109, thereby enabling the potential to accelerate the rate of therapeutic discovery for many aging-related diseases. This core leverages expertise in the methods and analysis of phenotypes derived from large-scale, nationally representative, normal aging cohorts, and makes these population-level data accessible to biologists. We will use up to 28 years of data from the U.S. Health and Retirement Study (HRS), a population representative sample of adults aged 50+ (N=18,000) who have high- density genotypic data, and transcription and methylation data (n~4,000), and over 16 years of data from the English Longitudinal Study of Ageing (ELSA) genetic sample (N=7,407). Available phenotypes include biomarkers curated from blood, methylated DNA or telomeres, as well as indices of functional ability, including physical status, disease conditions, cognitive functioning, frailty or mortality indicators, and environmental and behavioral phenotypes. Aims of the GTASC are to: (1) Accelerate translational research on human aging by interrogating findings derived from model systems in human population data; (2) Develop the resources and tools that can be expediently invoked for customized translational analyses; and (3) Develop new research directions using model systems, which entails designing and developing analytical plans for experimental and mechanism-based studies based on findings from human data. Increased access to cross-translational resources to validate model system findings in humans, generate additional hypotheses under natural human conditions, and use empirically-driven approaches for experimental designs will lead to an accelerated pace for gaining novel insights into processes in aging, and pave a faster route to intervention and treatment studies. The innovative combination of population genomics, biological markers, bioinformatics, and expertise in phenotype development to mark mortality, disease, and functionality is what gives this GTAS Core its uniqueness as a resource.

摘要-跨物种基因组翻译核心跨物种基因组翻译核心 (GTASC) 的总体目标与更大的使命相一致内森休克中心的，以推进对导致衰老的生物过程的转化研究通过跨学科合作取得相关成果。虽然在使用模型方面已经取得了很大进展系统来了解与健康寿命和疾病相关的衰老表型的生物过程，将模型生物的研究结果从生物学家翻译给临床医生，以验证遗传、转录组学、或表观遗传与人类特定年龄指标的关联发生得非常缓慢，带来的发现也是如此回到实验操作的模型系统。 GTASC 拥有一套独特的资源和专业知识促进正常衰老样本中的转化过程，具有性别和性别的多样性种族/族裔构成，年龄范围从 50 岁到 109 岁，从而有可能加速许多与衰老相关的疾病的治疗发现率。该核心利用了方法和技术方面的专业知识对来自大规模、具有全国代表性的正常老龄群体的表型进行分析，并做出生物学家可以获取这些人群水平的数据。我们将使用来自美国卫生和健康局长达 28 年的数据退休研究 (HRS)，50 岁以上成年人 (N=18,000) 的人口代表性样本，这些人具有高密度基因型数据、转录和甲基化数据（n~4,000）以及超过 16 年的数据英国衰老纵向研究 (ELSA) 基因样本 (N=7,407)。可用的表型包括从血液、甲基化 DNA 或端粒中提取的生物标志物，以及功能能力指数，包括身体状况、疾病状况、认知功能、虚弱或死亡指标以及环境和行为表型。 GTASC 的目标是： (1) 通过以下方式加速人类衰老的转化研究：询问从人口数据模型系统中得出的结果； (2) 资源开发可以方便地调用用于定制翻译分析的工具； (3) 开展新研究使用模型系统的方向，这需要设计和开发实验和分析计划基于人类数据发现的基于机制的研究。增加交叉翻译的机会验证人类模型系统发现的资源，在自然人类下产生额外的假设条件，并使用经验驱动的方法进行实验设计将导致加速步伐获得对衰老过程的新颖见解，并为干预和治疗研究铺平更快的道路。这群体基因组学、生物标记、生物信息学和表型专业知识的创新组合标记死亡率、疾病和功能的开发使 GTAS 核心具有独特性资源。