Metapangenomics of the Oral Microbiome

项目总结/摘要 口腔微生物组是一个复杂的多物种生态系统。解读微生物与每一种微生物的相互作用 其他微生物及其宿主栖息地对于了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。为了成功地调节微生物组，我们需要 了解细菌位点向性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共数据库中，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分析，并进行了足够深入的分析。而 虽然口腔中的大多数细菌物种都存在基因组信息，但还没有系统的分析， 哪些基因是主要物种的核心或附属基因-评估微生物功能的关键信息 以及用于选择用于体外模型的菌株。我们建议的科学前提是， 用口腔宏基因组信息进行泛基因组分析，因此称为元基因组学，将测试位点专家 这一假说，并提供了独特的，基因水平的见解，口腔微生物组的功能。 我们将从国家生物技术信息中心的高质量基因组构建泛基因组 （NCBI）的方法来鉴定口腔物种的核心基因和辅助基因。我们将绘制来自人类的宏基因组数据， 微生物组计划（HMP）和其他来源，对泛基因组，以评估哪些基因组实际上发生 在人的嘴里。通过口服位点的分析将在基因组水平上识别位点向性，从而评估位点- 专家假说我们将确定哪些基因是一个物种或菌株所特有的， 口腔生态位，我们将确定候选基因驱动程序的网站向性。我们分析的产品将被制成 通过扩展人类口腔微生物组数据库（HOMD）， 由Dewhirst博士开发，他是这个提案的PI。泛基因组将通过一个新的 由Eren博士创建的组学信息分析和可视化平台（Anvi 'o），该提案的PI。 该项目的影响是，它将建立一个基因组，生态框架，了解口腔 微生物组它将提供一个详细的，物种，菌株和基因水平的分析，口腔微生物组中， 个别口腔部位的情况。它将确定关键基因，为后续机制研究的网站向性，生态位 适应和发病机制。它将改善关键细菌物种的认证和纠错， 菌株该项目建立在HOMD，NCBI和HMP现有优势的基础上， 尖端基因组分析的结果，并为推动口腔微生物组研究奠定基础 进入泛基因组和宏基因组时代。

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.