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 口服微生物组是一个复杂的多种生态系统。破译微生物与每个相互作用 其他及其宿主栖息地对于理解口腔微生物组在健康和疾病中的作用至关重要 用于制定预防和治疗策略。为了成功调制微生物组，我们需要 了解细菌部位的基因组驱动因素和社区成员资格。大部分分子 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，但没有 我们在一个生态框架内使用适当的生物信息学工具和足够的深度分析了我们。尽管 对于大多数细菌物种而存在基因组信息，没有系统的分析 哪些基因是主要物种的核心或配件 - 评估微生物功能至关重要的信息 并用于选择体外模型的菌株。我们提议的科学前提是结合 pangenomic分析带有口服宏基因组信息，因此，宏基因组学将测试现场特殊主义者 假设并为口服微生物组功能提供独特的基因水平见解。 我们将在国家生物技术信息中心的高质量基因组中构建pangenomes （NCBI）识别口腔物种的核心和附属基因。我们将映射人类的核能数据 微生物组项目（HMP）和其他来源，用于评估哪些基因组实际发生 在人的嘴里。通过口头部位的分析将在基因组水平上识别现场疗法，从而评估该部位 专业假设。我们将确定哪些基因是某个物种独有的基因或占用特定的菌株 口服利基市场，我们将确定现场候选基因驱动因素。我们的分析产品将被制作 通过扩展人类口腔微生物组数据库（HOMD），可供口头研究社区 由DeWhirst博士开发，该提案的PI。 Pangenomes将通过新的 该提案的PI的Eren博士创建的OMICS信息分析和可视化平台。 该项目的影响是它将建立一个基因组，生态框架来理解口头 微生物组。它将提供对口腔微生物组的详细，物种，菌株和基因级分析 单个口头站点的上下文。它将确定关键基因，以进行现场向潮流的后续机械研究，利基市场 适应和发病机理。它将改善关键细菌物种的身份验证和错误纠正和错误纠正 菌株。该项目以HOMD，NCBI和HMP的现有优势为基础，可供研究人员使用 尖端基因组分析的结果，并为促进口腔微生物组研究奠定了基础 进入pangenomic和宏基因组时代。