Omics and Technology Core

组学和技术核心

• 批准号: 9795001
• 负责人: Rima F Kaddurah-Daouk
• 金额: $ 175.59万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9795001
• 关键词: Address; Algorithms; Alzheimer' s Disease; Archaea; Area; Bacteria; Biochemical; Biochemistry; Bioinformatics; Biological; Biological Models; Biotechnology; Blood; Brain; Brain imaging; Canada; Clinical; Collection; Communities; Complex; Computational Biology; Computational algorithm; Computer software; DNA; Data; Data Analyses; Data Provenance; Data Quality; Databases; Diet; Dimensions; Disease; Ensure; Environment; Feces; Funding; Generations; Genomics; Gold; Health Insurance Portability and Accountability Act; Human; Human Microbiome; Image; Indiana; Individual; Infrastructure; Institution; Institutional Review Boards; Investigation; Investments; Knowledge; Laboratories; Learning; Libraries; Magnetic Resonance Imaging; Mass Spectrum Analysis; Measurement; Medicine; Metagenomics; Methods; Molecular; Netherlands; Output; Pacific Northwest; Participant; Peripheral; Pharmaceutical Preparations; Phenotype; Problem Solving; Procedures; Process; Protocols documentation; Research; Research Personnel; Resolution; Sampling; Sampling Studies; Scanning; Secure; Ships; Shotguns; Site; Specialist; Specimen; Standardization; Structure; Systems Biology; Taxon; Technology; United States National Institutes of Health; Universities; Virus; Work; base; clinical phenotype; data integration; data management; data mining; experience; fecal metabolome; fungus; gut microbiome; gut microbiota; host microbiota; human model; imaging informatics; informatics infrastructure; innovation; interest; member; metabolome; metabolomics; metagenome; metagenomic sequencing; microbial; microbial community; microbiome; microbiome composition; microbiota profiles; multidisciplinary; relational database; sample collection; success

ABSTRACT – Core 1: Omics and Technology Core The Omics and Technology Core will act as a portal that interconnects all parts of the project, and will provide them with high-quality genomics, metabolomics and imaging data, to be integrated with the clinical and phenotyping information. To ensure maximal scientific output from the study samples, analysis will be conducted by leaders in each field and centers of excellence. The core will work closely with NCRAD, that will implement standardized procedures for collection of samples across the Alzheimer Centers, will coordinate shipment to our technology hubs for sample analysis, and enable tracking of chain of custody. The core will also work closely with the bioinformatics core and the Duke team to ensure gold-standard data management and to enable comprehensive data mining for the whole scientific community. The first sub-core will conduct state of the art metagenomics analysis of collected fecal samples to profile the entire microbial community inhabiting the gut. Genomic microbial DNA will be extracted and purified from the specimens using a commercially-available DNA kit, previously validated by the Human Microbiome Project. The culture- independent molecular methods will consist of shotgun metagenomic sequencing that provides the most comprehensive microbiota profile (bacteria, viruses, archaea, fungi). Rigorous sequence data analysis will utilize a set of advanced computational algorithms, according to the taxon-based or function-based data matrices. The second sub-core will conduct metabolomics analysis of blood and feces, to profile the host and gut-microbiota metabolomes. Comprehensive metabolome coverage is best achieved via combination of complementary approaches, and here we will apply various advanced methods of untargeted and targeted metabolomics. Untargeted metabolomics will utilize very high-resolution mass spectrometry (MS) to detect many thousands of compound spectra per sample, and employ complex algorithms and extensive data mining for identity elucidation. Conversely, targeted metabolomics platforms will utilize more sensitive and quantitative MS/MS measurement of only hundreds of compounds chosen according to existing evidence, biological interest and specifically the gut microbiome activity. Global metabolomics will be a cross-over between the two approaches, producing a full-scan high-resolution MS measurement of a few thousands of compounds, some identifiable via authentic standards, while others continuously added to the dynamic learning database of detected compounds, for further investigation. The third sub-core will gather quantitative magnetic resonance imaging of the brain, which contributes an additional layer to the phenotyping of the study participants. Building from the success of the ADNI project, a T1-weighted volumetric imaging will be utilized, to allow harmonization across the multiple sites. The imaging sub-core will coordinate the collection and aggregation of three- dimensional T1 imaging, and utilize existing ADCS image informatics infrastructure for high-throughput data capture, upload, and review.

摘要 – 核心 1：组学和技术核心 组学和技术核心将充当连接项目所有部分的门户，并将提供 为它们提供高质量的基因组学、代谢组学和成像数据，与临床和临床研究相结合 表型信息。为了确保研究样本获得最大的科学产出，分析将 由各个领域和卓越中心的领导者进行。该核心将与 NCRAD 密切合作，这将 实施阿尔茨海默病中心样本采集的标准化程序，将协调 运送到我们的技术中心进行样品分析，并实现监管链的跟踪。核心将 还与生物信息学核心和杜克大学团队密切合作，确保黄金标准的数据管理 并为整个科学界提供全面的数据挖掘。第一个子核心将进行 对收集的粪便样本进行最先进的宏基因组学分析，以描绘整个微生物群落 栖息于肠道。基因组微生物 DNA 将从样本中提取并纯化 市售 DNA 试剂盒，之前已通过人类微生物组计划验证。文化—— 独立的分子方法将包括鸟枪法宏基因组测序，它提供了最 全面的微生物群概况（细菌、病毒、古细菌、真菌）。严格的序列数据分析将 根据基于分类或基于函数的数据，利用一组先进的计算算法 矩阵。第二个子核心将对血液和粪便进行代谢组学分析，以分析宿主和 肠道微生物代谢组。全面的代谢组覆盖最好通过以下组合来实现 互补的方法，在这里我们将应用非目标和目标的各种先进方法 代谢组学。非靶向代谢组学将利用极高分辨率质谱 (MS) 来检测 每个样品有数千个化合物光谱，并采用复杂的算法和广泛的数据挖掘 用于身份澄清。相反，有针对性的代谢组学平台将利用更灵敏和定量的方法 仅对根据现有证据选择的数百种化合物进行 MS/MS 测量，生物 兴趣，特别是肠道微生物组活动。全球代谢组学将是两者的交叉 方法，对数千种化合物进行全扫描高分辨率 MS 测量，其中一些 可通过真实标准进行识别，而其他标准则不断添加到动态学习数据库中 检测到化合物，以供进一步研究。第三子核心将采集定量磁共振 大脑成像，这为研究参与者的表型分析提供了额外的一层。建筑 鉴于 ADNI 项目的成功，将利用 T1 加权体积成像来实现协调 跨多个站点。成像子核心将协调三个信息的收集和聚合： 三维 T1 成像，并利用现有的 ADCS 图像信息学基础设施获取高通量数据 捕获、上传和审查。