Molecular signatures of the periodontitis metagenome

描述（由申请人提供）：本申请涉及广泛的挑战领域（15）转化科学和特定的挑战主题15-DE-107：健康和疾病中口腔微生物组的宏基因组学。与美国复苏和再投资法案的目标一致，这项研究将创造多个新的就业机会，并涉及最先进的方法来解决21世纪的科学问题。我们建议使用最先进的宏基因组方法来研究广泛存在的人类疾病慢性牙周炎的微生物组。在宏基因组水平上几乎没有关于这种疾病的微生物群落的信息。人类微生物组计划（HMP）正在解决牙周健康的宏基因组问题，这里提出的研究将通过调查治疗前后慢性牙周炎的龈下微生物组来补充和利用HMP。我们的目标是确定区分牙周健康和疾病的微生物群落的功能宏基因组特征。我们将宏基因组签名定义为基因、DNA调控基序、致病元件和功能通路或相互作用。在这项研究中，我们计划首先通过比较治疗前后慢性牙周炎部位的宏基因组来确定是否存在区分牙周健康和疾病的宏基因组特征，以及它们是否与疾病的发病机制相关。一旦我们确定了这样的宏基因组签名，我们将通过评估健康和疾病状态的微生物组中所选宏基因组签名DNA的相对丰度，在不同的样本集中验证它们。这项研究将确定区分慢性牙周炎和健康的微生物遗传因素，为理解慢性牙周炎的分子机制提供基础，并为开发诊断，预防和管理疾病的创新临床方法提供依据。这项研究的重点是了解牙龈和牙齿之间的细菌中发现的哪些微生物基因会导致慢性牙龈疾病，这是一种常见的人类感染，影响了大约三分之一的美国成年人。我们将确定与牙龈疾病相关的微生物遗传特征，这些特征在健康的微生物群落中没有发现。这些遗传标记将提供重要的信息，可用于改善牙周（牙龈）疾病的诊断、预防和治疗。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (15) Translational Science, and specific Challenge Topic 15-DE-107: Metagenomics of the Oral Microbiome in Health and Disease. Consistent with the goals of the American Recovery and Reinvestment Act, this research will create multiple new jobs and involve state-of-the-art approaches to address 21st century scientific issues. We propose to use state-of-the-art metagenomic approaches to study the microbiome of the widespread human disease, chronic periodontitis. There is almost no information about the microbial community of this disease at the metagenomic level. The Human Microbiome Project (HMP) is addressing the metagenome of periodontal health, and the studies proposed here will complement and leverage the HMP by investigating the subgingival microbiome of chronic periodontitis prior to and after treatment. Our goal is to identify functional metagenomic signatures of the microbial community that differentiate periodontal health and disease. We define metagenomic signatures as genes, DNA regulatory motifs, pathogenic elements, and functional pathways or interactions. In this study, we plan to first determine whether there are metagenomic signatures that differentiate periodontal health and disease, and whether they are related to the pathogenesis of the disease, by comparing the metagenomes from sites of chronic periodontitis before and after treatment. Once we identify such metagenomic signatures, we will validate them in a different sample set by assessing the relative abundance of selected metagenomic signature DNA in the microbiomes of health and disease states. This study will define the microbial genetic elements that distinguishes chronic periodontitis from health, will provide a foundation for understanding the molecular mechanisms of chronic periodontitis, and will provide for the development of innovative clinical approaches to diagnosing, preventing and managing the disease. The research proposed in this application focuses on understanding which microbial genes found in bacteria in the pocket between the gums and the teeth contribute to chronic gum disease, a common human infection that affects about a third of US adults. We will identify microbial genetic signatures associated with gum disease that are not found in healthy microbial communities. These genetic signatures will provide important information that can be used to improve the diagnosis, prevention and treatment of periodontal (gum) diseases.