Metapangenomics of the Oral Microbiome

口腔微生物组的宏基因组学

• 批准号: 10296963
• 负责人: Gary G Borisy
• 金额: $ 65.01万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10296963
• 关键词: Address; Bacteria; Biotechnology; Candidate Disease Gene; Communities; Complex; Data; Databases; Dental Plaque; Disease; Ecosystem; Foundations; General Practitioners; Genes; Genetic; Genome; Genomics; Goals; Habitats; Health; Human; Human Microbiome; Individual; Knowledge; Maps; Metagenomics; Microbe; Molecular; Mouth Diseases; Oral; Oral cavity; Organism; Pathogenesis; Population; Prevalence; Preventive; Research; Research Personnel; Resources; Role; Saliva; Sampling; Site; Source; Specialist; Specificity; Testing; Therapeutic; Tongue; Tooth structure; Tropism; Visualization; base; bioinformatics tool; follow-up; human data; improved; in vitro Model; insight; knowledge base; microbial; microbial genome; microbiome; microbiome research; oral microbiome; pan-genome; whole genome

Project Summary/Abstract The oral microbiome is a complex multispecies ecosystem. Deciphering the interactions of microbes with each other and their host habitats is essential for understanding the oral microbiome's role in health and disease and for developing preventive and therapeutic strategies. To successfully modulate the microbiome we need to understand the genomic drivers of bacterial site tropisms and community membership. Much of the molecular data needed to address these fundamental questions already exists in publicly available databases, but has not been analyzed within an ecologic framework using appropriate bioinformatic tools and in sufficient depth. While genome information exists for most bacterial species in the mouth, there has been no systematic analysis of what genes are core or accessory for the major species – information critical for assessing microbial function and for selecting strains for in vitro models. The scientific premise of our proposal is that the combination of pangenomic analysis with oral metagenomic information, hence metapangenomics, will test the site-specialist hypothesis and provide unique, gene-level insights into the function of the oral microbiome. We will construct pangenomes from high-quality genomes in the National Center for Biotechnology Information (NCBI) to identify core and accessory genes of oral species. We will map metagenomic data from the Human Microbiome Project (HMP), and other sources, onto the pangenomes to assess which genomes actually occur in the human mouth. Analysis by oral site will identify site-tropisms at the genomic level, thus evaluating the site- specialist hypothesis. We will determine which genes are unique to a species or strain occupying a particular oral niche, and we will identify candidate gene drivers of site tropism. The products of our analysis will be made available to the oral research community by expanding the Human Oral Microbiome Database (HOMD), developed by Dr. Dewhirst, a PI on this proposal. Pangenomes will be made available interactively via a new platform for Analysis and Visualization of Omics Information (Anvi'o) created by Dr. Eren, a PI on this proposal. The impact of the project is that it will establish a genomic, ecologic framework for understanding the oral microbiome. It will provide a detailed, species, strain- and gene-level analysis of the oral microbiome in the context of individual oral sites. It will identify key genes for follow-up mechanistic studies on site tropisms, niche adaptation, and pathogenesis. It will improve authentication and error-correction of key bacterial species and strains. The project builds on the existing strengths of HOMD, NCBI and HMP, makes available to researchers the results of cutting-edge genomic analysis, and lays the groundwork for propelling oral microbiome research into the pangenomic and metagenomic era.

项目摘要/摘要 口腔微生物群是一个复杂的多物种生态系统。破译微生物与每种微生物之间的相互作用 其他及其寄主栖息地对于了解口腔微生物群在健康和疾病中的作用以及 用于制定预防和治疗策略。为了成功地调节微生物群，我们需要 了解细菌位置取向和社区成员的基因组驱动因素。大部分的分子 解决这些基本问题所需的数据已经存在于公开可用的数据库中，但还没有 在生态框架内使用适当的生物信息学工具进行了足够深入的分析。而当 基因组信息存在于口腔中的大多数细菌物种中，还没有系统地分析 哪些基因是主要物种的核心或附属基因？对评估微生物功能至关重要的信息 并用于为体外模型选择菌株。我们建议的科学前提是 用口头元基因组学信息进行的泛基因组学分析，因此元基因组学，将考验现场专家 并对口腔微生物组的功能提供独特的、基因水平的见解。 我们将在国家生物技术信息中心用高质量的基因组构建泛基因组 (NCBI)鉴定口腔物种的核心和辅助基因。我们将映射来自人类的元基因组数据 微生物组计划(HMP)和其他来源到盘根体上，以评估哪些基因组实际发生 在人类的嘴里。通过口腔部位的分析将在基因组水平上识别部位偏向性，从而评估部位- 专家假说。我们将确定哪些基因是某一物种或菌株所特有的 口腔生态位，我们将确定位点趋向性的候选基因驱动因素。我们的分析结果将被制作成 通过扩展人类口腔微生物组数据库(HOMD)向口腔研究界提供， 由DeWhirst博士开发，他是这项提议的PI。Pangenome将通过一个新的 OMICS信息分析和可视化平台(Anvi‘o)由Eren博士创建，他是这项提议的PI。 该项目的影响是，它将建立一个理解口腔的基因组生态框架 微生物组。它将提供对口腔微生物群的详细、种类、菌株和基因水平的分析 个别口腔站点的上下文。它将为站点取向、生态位的后续机制研究确定关键基因 适应，以及发病机制。它将改进关键细菌物种的认证和纠错，并 菌株。该项目建立在HOMD、NCBI和HMP现有优势的基础上，向研究人员提供 尖端基因组分析结果，为推进口腔微生物组研究奠定了基础 进入了泛基因组和超基因组时代。