Omics and Technology Core

摘要-核心1：组学和技术核心 OMICS和技术核心将充当互连项目所有部分的门户，并将提供 它们具有高质量的基因组学、代谢组学和成像数据，将与临床和 表型信息。为了确保从研究样本中获得最大的科学产出，将进行分析 由每个领域和卓越中心的领导者进行。核心将与NCRAD密切合作，这将 在阿尔茨海默病中心实施标准化的样本收集程序，将协调 运输到我们的技术中心进行样本分析，并支持跟踪保管链。核心将会 还与生物信息学核心和杜克团队密切合作，以确保黄金标准的数据管理 并使整个科学界能够进行全面的数据挖掘。第一个子核将进行 对采集的粪便样本进行最新的元基因组分析，以描述整个微生物群落 寄居在肠子里。从样本中提取和纯化基因组微生物DNA将使用 商品化的DNA试剂盒，之前由人类微生物组项目验证。文化-- 独立的分子方法将包括鸟枪式元基因组测序，它提供了最多的 全面的微生物区系概况(细菌、病毒、古生菌、真菌)。严格的序列数据分析将 根据基于分类单元或基于函数的数据，使用一套先进的计算算法 矩阵。第二个分核心将对血液和粪便进行代谢组学分析，以描述宿主和 肠道微生物区系代谢物。全面的代谢组覆盖最好是通过以下组合实现 相辅相成的方法，在这里我们将应用各种先进的无针对性和针对性的方法 代谢组学。非靶向代谢组学将利用非常高分辨率的质谱学(MS)来检测 每个样本有数千个化合物光谱，并使用复杂的算法和广泛的数据挖掘 以确定身份。相反，靶向代谢组学平台将利用更敏感和更定量的 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，特别是肠道微生物群的活动。全球代谢组学将是两者的交叉 方法，产生了对数千种化合物的全扫描高分辨率MS测量，一些 可以通过可信的标准识别，而其他的不断添加到动态学习数据库中 检测到的化合物，以供进一步调查。第三个亚核将收集定量磁共振 大脑成像，这为研究参与者的表型提供了额外的一层。建房 由于ADNI项目的成功，将使用T1加权的体积成像，以实现协调 在多个站点之间。成像子核将协调收集和聚合三个- 维度T1成像，并利用现有的ADCS图像信息学基础架构实现高通量数据 捕获、上传和查看。

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.