Metapangenomics of the Oral Microbiome

口腔微生物组的宏基因组学

基本信息

批准号：
10651901
负责人：
Gary G Borisy
金额：
$ 59.68万
依托单位：
ADA FORSYTH INSTITUTE, INC.
依托单位国家：
美国
项目类别：
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

项目摘要

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.

项目概要/摘要口腔微生物组是一个复杂的多物种生态系统，需要破译微生物之间的相互作用。其他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为了成功地调节微生物组，我们需要制定预防和治疗策略。了解细菌位点趋向性和群落成员的基因组驱动因素。解决这些基本问题所需的数据已经存在于公开数据库中，但尚未存在已使用适当的生物信息学工具在生态框架内进行了足够深入的分析。口腔中大多数细菌种类都存在基因组信息，但尚未进行系统分析哪些基因是主要物种的核心或附属基因——对于评估微生物功能至关重要的信息我们建议的科学前提是结合以下因素。利用口腔宏基因组信息进行的泛基因组分析，即宏泛基因组学，将考验现场专家假设并为口腔微生物组的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利用高质量基因组构建泛基因组 (NCBI) 来识别口腔物种的核心和辅助基因，我们将绘制人类宏基因组数据。微生物组计划 (HMP) 和其他来源对泛基因组进行评估，以评估哪些基因组实际存在通过口腔位点进行分析将在基因组水平上识别位点向性，从而评估位点我们将确定哪些基因是特定物种或菌株所独有的。口腔生态位，我们将确定位点向性的候选基因驱动因素，我们的分析产品将被制成。通过扩展人类口腔微生物组数据库（HOMD）向口腔研究界提供，该提案的 PI 由 Dewhirst 博士开发，将通过新的交互方式提供。由该提案的 PI Eren 博士创建的组学信息分析和可视化平台 (Anvi'o)。该项目的影响在于它将建立一个基因组、生态框架来理解口腔它将提供口腔微生物组的详细物种、菌株和基因水平分析。它将确定针对位点取向、生态位的后续机制研究的关键基因。它将改善关键细菌物种的鉴定和纠错。该项目建立在 HOMD、NCBI 和 HMP 的现有优势之上，可供研究人员使用。尖端基因组分析的结果，为推动口腔微生物组研究奠定基础进入全基因组和宏基因组时代。