A Foundation for the Oral Microbiome and Metagenome

口腔微生物组和宏基因组的基础

• 批准号: 10596650
• 负责人: Floyd E Dewhirst
• 金额: $ 125.55万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596650
• 关键词: Address; Aerodigestive Tract; Animal Model; Bacteria; Bacteriophages; Bibliography; Biochemical; Biological; Biology; Chlorobi; Clinical; Communities; Data; Databases; Dental caries; Diagnosis; Disease; Foundations; Funding; Genetic; Genome; Genomics; Goals; Health; Health Professional; Heart Diseases; Human; Human Microbiome; In Vitro; Investigation; Knowledge; Laboratories; Link; Metabolism; Metagenomics; Methods; Microbe; Mouth Diseases; Mus; Names; Nose; Oral; Oral Microbiology; Oral cavity; Oral health; Organism; Outcome; Pathogenicity; Persons; Phenotype; Phylogenetic Analysis; Play; Premature Birth; Proteomics; Radiation; Refractory; Research; Research Personnel; Resources; Ribosomal RNA; Role; Sampling; Scheme; Scientist; Site; Stroke; Structure; Taxon; Taxonomy; Technology; Treponema; Virus; bioinformatics tool; dark matter; experimental study; genetic information; genome resource; genomic data; host-microbe interactions; improved; in vivo; member; metabolomics; metagenome; methylome; microbial; microbiome; microbiome analysis; microbiome components; microbiome research; novel; oral bacteria; oral microbial community; oral microbiome; preference; prevent; tool; transcriptomics; web-accessible; whole genome

The major objective of the proposed research is to build a foundation of genomic information and resources for the scientific community investigating how the oral microbiome contributes to human health and disease. In prior years of this project we created the expanded Human Oral Microbiome Database (eHOMD), a web accessible taxonomic and genomic database with taxon descriptions and microbiome analysis tools. We cultivated reference strains for previously uncultured oral & nasal bacteria to facilitate in vivo and in vitro experimentation, and we leveraged the sequencing power of the Human Microbiome Project as well as our laboratory's sequencing facility to generate genome sequences for the majority of oral microbial taxa. In the proposed project period, our goal is to fill in the major remaining gaps that present a barrier to full realization of the potential of `omics technologies to drive discoveries in oral microbiology. Our strategy involves three specific aims. The first Aim encompasses improvements to eHOMD itself, including a significant expansion of eHOMD to include the viruses that infect oral & nasal microbes. To allow investigators to do more rigorous microbiome research in mice, a Mouse Oral Microbiome Database (MOMD) will be released so that investigators can accurately document the composition of their mice's oral microbiome. Completion of this aim will allow investigators to link phenotypic, clinical, genomic and bibliographic information to precisely-defined bacterial and phage taxa. The Second Aim addresses the fact that nearly one-third of the 771 eHOMD bacterial taxa have no known cultivated isolates. We will bring into cultivation strains of oral bacteria that are currently refractory to cultivation and make these strains available to the research community. For bacteria that are only sporadically abundant we will use information on abundance of uncultivated bacteria in 20 subjects to guide sampling efforts, and for bacteria that are common but difficult to grow we will use co-cultivation approaches that we have previously employed successfully to isolate and grow 30 strains of the previously uncultivable Saccharibacteria. In the third Aim we will obtain genome sequences for eHOMD taxa currently lacking genome information. Using long-read sequencing we will produce closed genomes of cultivable strains, including strains isolated in Aim 2. To provide genome coverage for remaining uncultivable taxa, we will add high quality Metagenome-Assembled Genomes (MAGs) to eHOMD. Successful completion of the three Aims of this project will increase the genomic coverage of oral and nasal taxa to the point where eHOMD is an exemplary reference database that enables studies using metagenomics, transcriptomics, proteomics, and metabolomics to understand the interactions of oral microbes with one another and with their host. The genome information, tools, and strains generated by this project will serve as a permanent foundation and resource for investigations on the role of the oral microbiome in human health and disease.

这项研究的主要目标是建立基因组信息和资源的基础， 科学界调查口腔微生物组如何有助于人类健康和疾病。在 在该项目的前几年，我们创建了扩展的人类口腔微生物组数据库（eHOMD）， 可访问的分类和基因组数据库，包括分类描述和微生物组分析工具。我们 培养的参考菌株，用于先前未培养的口腔和鼻腔细菌，以促进体内和体外 我们利用了人类微生物组计划的测序能力， 该实验室的测序设施，以产生大多数口腔微生物类群的基因组序列。在 在拟议的项目期间，我们的目标是填补阻碍全面实现 “组学”技术推动口腔微生物学发现的潜力。我们的战略包括三个方面 具体目标。第一个目标包括对eHOMD本身的改进，包括对 eHOMD包括感染口腔和鼻腔微生物的病毒。为了让调查人员能够更严格地 在小鼠的微生物组研究中，将发布小鼠口腔微生物组数据库（MOMD）， 研究人员可以准确地记录小鼠口腔微生物组的组成。实现这一目标 将允许研究者将表型、临床、基因组和书目信息与精确定义的 细菌和噬菌体分类群。第二个目标解决了771 eHOMD中近三分之一的 细菌分类群没有已知的培养分离物。我们将培养口腔细菌菌株， 目前难以培养，并使这些菌株可用于研究界。For bacteria that 我们将使用20个受试者中未培养细菌丰度的信息， 指导采样工作，对于常见但难以生长的细菌，我们将使用共培养 我们以前成功地使用这种方法分离和培养了30种以前的菌株， 不可培养的酵母菌在第三个目标中，我们将获得eHOMD分类群的基因组序列， 缺乏基因组信息。使用长读序测序，我们将产生可培养菌株的封闭基因组， 包括在Aim 2中分离的菌株。为了提供剩余的不可培养类群的基因组覆盖率，我们将添加 高质量的宏基因组组装基因组（MAG）到eHOMD。圆满完成三大目标 该项目的实施将增加口腔和鼻腔分类群的基因组覆盖率，使eHOMD成为一种 示例性参考数据库，其使得能够使用宏基因组学、转录组学、蛋白质组学和 代谢组学，以了解口腔微生物相互之间以及与宿主之间的相互作用。的 该项目产生的基因组信息、工具和菌株将作为一个永久的基础， 研究口腔微生物组在人类健康和疾病中的作用的资源。