Microbiome Core: IDEAL shapes vaccine response, susceptibility to respiratory infectious disease and asthma

微生物组核心：IDEAL 影响疫苗反应、呼吸道传染病和哮喘的易感性

• 批准号: 10589807
• 负责人: Bill Mohn
• 金额: $ 11.04万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-10 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589807
• 关键词: Address; American; Asthma; Benchmarking; Canada; Child; Childhood; Clinical; Cloud Service; Collaborations; Communicable Diseases; DNA; Data; Development; Ensure; Foundations; Gene Frequency; Generations; Health; Immune; Infant; Infection; Investigation; Lead; Life; Link; Measures; Metabolism; Metagenomics; Molecular; Nasopharynx; Nose; Outcome; PRTN3 gene; Pathologist; Phenotype; Population; Predisposition; Prokaryotic Cells; Protocols documentation; Publishing; Resolution; Respiratory Tract Infections; Role; Sampling; Secure; Shapes; Shotgun Sequencing; Shotguns; Standardization; Supervision; Taxonomy; Western Australia; Work; clinical phenotype; clinical predictors; cohort; college; comparative; computerized tools; data management; insight; large datasets; metagenome; microbiome; microbiome analysis; microbiome research; nasal microbiome; programs; prospective; quality assurance; rRNA Genes; respiratory; therapeutic target; vaccine response

Microbiome Core, Summary Mounting evidence indicates a strong association between the microbiome and immune development in early life (IDEAL). More specifically, we and others are providing growing evidence for a role of the microbiome in the three clinical outcomes targeted in this IDEAL proposal: vaccine response, respiratory infection, and asthma. In support of the proposed IDEAL program, the Microbiome Core (MBC) will generate and analyze shotgun metagenomes from 1300 nasal and fecal samples from the existing Rochester Combined Cohort (RCC) and the prospective Rochester IDEAL Cohort (RIC). Data generation and analyses will be conducted with rigorous quality assurance measures. The microbiome data, paired with clinical and other omic data, will be exceptional for an IDEAL study, and the nasal metagenomes will be unprecedented in scope and depth of microbiome coverage. The premise at the foundation of the MBC is that the microbiome is a key driver of IDEAL. As a consequence, we hypothesize that the microbiome will contribute to key objectives of the overall IDEAL proposal, (i) early prediction of clinical phenotypes, (ii) delineation of molecular endotypes among the phenotypes, and (iii) identification of actionable therapeutic targets. Further, comparative analysis of microbiomes will provide mechanistic insight to interactions between the microbiome and IDEAL. The MBC has two Specific Aims: SA1 is to generate microbiome data products, (i) high-quality shotgun metagenome sequence data, (ii) taxonomic profiles, and (iii) functional profiles. The data products will be transferred to the Data Management Core (DMC) to support Projects (PR) 1-3 in addressing the above key objectives. SA2 is microbiome analysis using both taxonomic and functional profiles, focussing on diversity, differential abundance, temporal dynamics, and interactions. The main purpose of the MBC analyses will be ecological and mechanistic interpretation of microbiome variability among the clinical phenotypes and molecular endotypes.

微生物组核心，总结 越来越多的证据表明，微生物组与早期免疫发育之间存在密切联系。 生活（理想）。更具体地说，我们和其他人正在提供越来越多的证据证明微生物组在以下方面的作用： IDEAL提案中针对的三种临床结果：疫苗反应、呼吸道感染和 哮喘为了支持拟议的IDEAL计划，微生物组核心（MBC）将生成和分析 来自现有罗切斯特联合队列的1300个鼻和粪便样本的鸟枪宏基因组 (RCC)和前瞻性罗切斯特理想队列（RIC）。将进行数据生成和分析 严格的质量保证措施。微生物组数据与临床和其他组学数据相结合， 对于IDEAL研究来说，这将是一个例外，鼻宏基因组的范围和深度将是前所未有的。 微生物覆盖率。MBC基础的前提是微生物组是微生物的关键驱动力。 理想.因此，我们假设微生物组将有助于实现总体的关键目标。 IDEAL建议，（i）临床表型的早期预测，（ii）分子内型之间的划定 表型，和（iii）鉴定可行的治疗靶点。此外，比较分析 微生物组将为微生物组和IDEAL之间的相互作用提供机制见解。MBC已 两个具体目标：SA 1是生成微生物组数据产品，（i）高质量的鸟枪宏基因组 序列数据，（ii）分类学概况，和（iii）功能概况。数据产品将传输到 数据管理核心（DMC）支持项目（PR）1-3实现上述关键目标。SA 2是 微生物组分析使用分类和功能概况，重点是多样性，差异 丰度、时间动态和相互作用。MBC分析的主要目的是生态 临床表型和分子生物学之间微生物组变异性的机制解释 内型