Multi-Omics Core C

多组学核心 C

• 批准号: 10555124
• 负责人: Kelly Hyndman
• 金额: $ 34.63万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-15 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10555124
• 关键词: 16S ribosomal RNA sequencing; ATAC-seq; Acetylation; Address; Adult; Animals; Applications Grants; Basic Science; Bioinformatics; Biometry; Cell Nucleus; Cells; Chromatin; Chromatin Structure; Clinical; Cost Savings; DNA; DNA Methylation; DNA Sequencing Facility; Data; Data Analyses; Data Collection; Deposition; Ensure; Environment; Experimental Designs; Genes; Genomics; Goals; Histone Deacetylase; Human; Institution; Kidney; Life; Link; Liquid Chromatography; Lysine; Mass Spectrum Analysis; Mediating; Methods; Preparation; Proteins; Proteomics; Protocols documentation; Quality Control; RNA; Reagent; Regulation; Reproducibility; Resolution; Risk; Risk Factors; Rodent; Sampling; Standardization; Structure; Techniques; Technology; Testing; Tissues; Transcriptional Regulation; Volatile Fatty Acids; Work; bench to bedside; cardiovascular disorder risk; data management; data submission; early life stress; epigenetic regulation; epigenome; epigenomics; experience; experimental study; genome-wide analysis; gut microbiome; innovation; innovative technologies; member; metabolome; metabolomics; methylome; microbial; microbiome; microbiome research; multiple omics; new technology; repository; resilience; sample collection; single nucleus RNA-sequencing; synergism; tandem mass spectrometry; technology platform; transcriptome; transcriptome sequencing; transcriptomics

MULTI-OMICS CORE C SUMMARY This PPG is addressing an important hypothesis that early life stress (ELS) leads to reprogramming throughout the body resulting in an increased risk of developing CVD in adulthood. The mechanistic links between ELS and CVD and resilience in adulthood is not established. Epigenetic regulation of transcription or the gut microbiome and microbial-derived factors are hypothesized to be sensitive to ELS and may be modifiable to mediate resiliency. The primary goal and function of the Multi-omics Core (Core C) is to provide start-of-the-art processing of samples for determination of transcriptomes, DNA methylomes, DNA chromatin accessibility, metabolomes, and microbiomes required by all Projects. The objective of the Core is to provide consistency and rigor in the multi-omics experiments and provide innovative technologies to meet the goals of the Projects. The specific aims of Core C are: Aim 1 Transcriptomic and epigenomic determination. The epigenome is an important connection between the environment and the genes expressed in each cell (transcriptomes) and it is regulated by DNA methylation and chromatin structure (accessibility). Core C will facilitate determination of transcriptomes, and epigenome global DNA methylation and chromatin accessibility for the Projects. Aim 2: Microbiome and metabolite profiling. In this PPG, it is hypothesized that ELS results in gut microbial diversity changes that result in significant alterations to circulating short chain fatty acids (SCFA) or other metabolites. Core C will prepare samples for microbiome 16S sequencing for identifying and quantifying microbial diversity. The Core will also prepare samples for SCFA and untargeted metabolite determination by mass spectrometry. Aim 3: Evaluating new technologies, optimization while promoting fiscal responsibility. In this era of multi-omics, technologies are rapidly evolving. Thus, to provide the Projects with the latest technologies to test their hypotheses, Core C will evaluate new technological platforms. Core C will optimize all protocols for sample preparation for the multi-omics approaches listed above. By centralizing the mutli-omic sample preparation in Core C, we will purchase kits and reagents in bulk leading to substantial cost savings. Core C will interact directly with all Projects, receive clinical samples from Core B, and work directly with Core A for sample identification, curating, data deposition and analyses, and data management. Core A will complete all bioinformatics and biostatistical analyses for data generated in Core C. The approaches used in Core C ensure that the PPG is using the latest technologies for determining mechanisms of ELS induced cardiovascular disease risk with a bench to beside approach.

MULTI-OMICS CORE C概要 这个PPG解决了一个重要的假设，即早期生活压力（ELS）导致整个过程中的重新编程 导致成年期患CVD的风险增加。ELS和 成年期的CVD和恢复力尚未建立。转录或肠道微生物组的表观遗传调节 和微生物源性因子被假设为对ELS敏感，并且可能是可修饰的， 恢复力多组学核心（核心C）的主要目标和功能是提供最先进的处理 用于测定转录组、DNA甲基化组、DNA染色质可及性、代谢组 和微生物组。核心的目标是提供一致性和严谨性， 多组学实验，并提供创新技术，以实现项目的目标。具体目标 目的1转录组学和表观基因组学测定。表观基因组是一个重要的 环境与每个细胞中表达的基因（转录组）之间的联系，并受到调控 DNA甲基化和染色质结构（可及性）。核心C将有助于确定转录组， 和表观基因组全局DNA甲基化和染色质可及性。目标2：微生物组和 代谢物分析。在该PPG中，假设ELS导致肠道微生物多样性变化， 导致循环短链脂肪酸（SCFA）或其它代谢物的显著改变。核心C将 制备用于微生物组16 S测序的样品，以鉴定和量化微生物多样性。核心 还将通过质谱法制备用于SCFA和非靶向代谢物测定的样品。目标三： 评估新技术，优化，同时促进财政责任。在这个多元经济时代， 技术正在迅速发展。因此，为项目提供最新技术，以测试其 假设，核心C将评估新的技术平台。核心C将优化样本的所有方案 为上述多组学方法做准备。通过将多组学样品制备集中在 核心C，我们将批量购买试剂盒和试剂，从而节省大量成本。核心C将直接交互 与所有项目合作，接收来自核心B的临床样本，并直接与核心A合作进行样本鉴定， 策展、数据存储和分析以及数据管理。核心A将完成所有生物信息学和 核心C中生成数据的生物统计学分析。核心C中使用的方法确保PPG是 使用最新技术确定ELS诱导心血管疾病风险的机制， 长凳到旁边的方法。