Community Genomics of the Human Oral Microbiome

描述：人类口腔是超过700种微生物的复杂群落的家园，在口腔健康和疾病中发挥着核心作用。在我们的应用中，这种口腔微生物群落或口腔微生物组被视为一个单一的动态实体，其行为和组成在空间（不同个体的不同口腔生态位），时间和扰动方面存在变化。尽管这个社区在维持人类健康和引发口腔疾病方面至关重要，但其行为的遗传基础尚未得到很好的探索。本申请的长期目标是在基因组水平上全面了解口腔微生物群落，从而促进口腔健康，改善或预防疾病。我们将通过表征健康牙周和粘膜组织受试者口腔微生物组中的相对基因和基因组丰度以及基因表达来实现这些目标，然后将我们的分析扩展到与慢性牙周病相关的口腔微生物组。该应用程序的数据不仅将用于建立口腔微生物组中基因的数据库，还将为探索基因丰度和表达以及研究微生物组与人类宿主的相互作用带来新的实验范式。 本申请的具体目标是：目标1。表征健康人类口腔微生物组的基因和基因组含量。我们的方法包括随机和靶向质粒和fosmid基因组文库的高通量测序以及功能基因和基因家族的分类。目标2.表征与慢性牙周炎相关的口腔微生物组的基因和基因组含量。目标3.开发用于口腔微生物组数据的社区基因组工具。将建立一个口腔微生物组基因数据库，供科学界使用。将开发具有在目标1和2中鉴定的约2，000个基因的高密度DNA微阵列，其最终目标是鉴定预测临床自然史和对操作的反应的基因丰度和表达模式。这项工作的预期长期效益将是对人类口腔生态系统的革命性理解以及口腔疾病分类和管理的新方法。

DESCRIPTION: The human oral cavity is home to a complex community of >700 microorganisms with a central role in oral health and disease. In our application, this oral microbial community, or oral microbiome, is viewed as a single dynamic entity, with variation in its behavior and composition across space (different oral niches in different individuals), time, and with perturbation. Despite the critical importance of this community in maintaining human health and provoking oral disease, the genetic basis for its behavior has not been well explored. The long-term objectives of this application are to develop a comprehensive understanding of the oral microbial community at the genomic level so that oral health can be promoted, and disease ameliorated or prevented. We will address these goals by characterizing relative gene and genome abundance and gene expression in the oral microbiome in subjects with healthy periodontal and mucosal tissues, and then extend our analysis to the oral microbiome associated with chronic periodontal diseases. Data from this application will not only be used to build a database for genes in the oral microbiome, but will also lead to new experimental paradigms for exploring gene abundance and expression, and examining the interaction of the microbiome with the human host. The Specific Aims of this application are: Aim 1. Characterize the gene and genome content of the healthy human oral microbiome. Our approaches include high-throughput sequencing of random and targeted plasmid and fosmid genomic libraries and classification of functional genes and gene families. Aim 2. Characterize the gene and genome content of the oral microbiome associated with chronic periodontitis. Aim 3. Development of community genomic tools for oral microbiome data. An oral microbiome gene database will be created for use by the scientific community. A high-density DNA microarray with approximately 2,000 genes identified in Aims 1 and 2 will be developed with the ultimate goal of identifying patterns of gene abundance and expression that predict clinical natural history and response to manipulation. Among the expected long-term benefits of this work will be a revolutionized understanding of the human oral ecosystem and new approaches for classification and management of oral diseases.