New Tools for Understanding the Composition and Dynamics of Microbial Communities

了解微生物群落组成和动态的新工具

• 批准号: 7897769
• 负责人: ROB KNIGHT
• 金额: $ 38.54万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-26 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7897769
• 关键词: Accounting; Adult; Affect; Age; Archaea; Bacteria; Biological; Biological Phenomena; Biology; Cells; Child; Communities; Computer Analysis; Crohn' s disease; Data; Data Analyses; Data Set; Deposition; Descriptor; Development; Diet; Dimensions; Discipline; Disease; Ecology; Ensure; Environment; Family; Genes; Genetic Variation; Geography; Habitats; Health; Health Status; Human; Human Genome; Human Microbiome; Human body; Individual; Licensing; Life; Mathematics; Measures; Medical; Metagenomics; Methods; Metric; Microbe; Nature; Obesity; Organism; Outcome; Phenotype; Phylogenetic Analysis; Phylogeny; Play; Population; Public Health; Recommendation; Research Personnel; Ribosomal RNA; Role; Sampling; Simulate; Source; Statistical Methods; Structure; Techniques; Therapeutic; Time; Validation; Variant; Work; base; clinically relevant; computerized tools; design; expectation; fungus; improved; infancy; innovation; interest; large scale simulation; markov model; metagenomic sequencing; microbial; microbial community; microbiome; models and simulation; new technology; novel diagnostics; open source; public health relevance; sex; tool; transmission process; trend; Accounting; Adult; Affect; Age; Archaea; Bacteria; Biological; Biological Phenomena; Biology; Cells; Child; Communities; Computer Analysis; Crohn' s disease; Data; Data Analyses; Data Set; Deposition; Descriptor; Development; Diet; Dimensions; Discipline; Disease; Ecology; Ensure; Environment; Family; Genes; Genetic Variation; Geography; Habitats; Health; Health Status; Human; Human Genome; Human Microbiome; Human body; Individual; Licensing; Life; Mathematics; Measures; Medical; Metagenomics; Methods; Metric; Microbe; Nature; Obesity; Organism; Outcome; Phenotype; Phylogenetic Analysis; Phylogeny; Play; Population; Public Health; Recommendation; Research Personnel; Ribosomal RNA; Role; Sampling; Simulate; Source; Statistical Methods; Structure; Techniques; Therapeutic; Time; Validation; Variant; Work; base; clinically relevant; computerized tools; design; expectation; fungus; improved; infancy; innovation; interest; large scale simulation; markov model; metagenomic sequencing; microbial; microbial community; microbiome; models and simulation; new technology; novel diagnostics; open source; public health relevance; sex; tool; transmission process; trend

DESCRIPTION (provided by applicant): The microbes that inhabit human bodies outnumber the human cells by an order of magnitude, and impact many aspects of health and disease including obesity, vaginosis, and Crohn's disease. Understanding this endogenous microbiota is emerging as a key extension of efforts to understand the human genome and the role of genetic variation on health and disease. The Human Microbiome Project (HMP) will characterize microbial communities in a large number of individual healthy humans using metagenomic sequencing. Consequently, new methods for interpreting sequence data to understand microbial community composition and dynamics are urgently needed. This project unites disciplines ranging from ecology to evolutionary biology to applied mathematics, to develop new methods for understanding which body habitats are more or less similar in terms of their microbial communities, by evaluating measures of microbial diversity and change, and creating needed new metrics of community composition. This will enable understanding of how clinically relevant parameters such as age, sex, or the pH of specific body habitats affect these communities, and of how the dynamics of change in microbial communities within an individual, in transmission between individuals, and in transmission between humans and the environment. This project is directly responsive to the Roadmap RFA for Development of New tools for Computational Analysis of Human Microbiome Project Data. The specific aims of this proposal are: Aim 1. Develop, characterize, and apply enriched descriptors of microbial community diversity. Aim 2. Develop methods for describing how human microbial communities vary over time and space. Aim 3. Develop new methods for tracing the flow of organisms among different communities. Some key aspects of the proposed work are: the development of new statistical methods for estimating microbial diversity within a body habitat; development of enriched methods for describing microbial community diversity; exhaustive validation of methods for comparing microbial communities through large-scale simulations and by using the largest available data sets that characterize microbial communities empirically; and the development of new methods for tracing the sources of the microbes that inhabit the human body using both marker genes and whole-metagenome data. Key outcomes include the ability to help determine the extent to which there is a core human microbiome, and how best to sample human microbial diversity. All methods developed will be made available under open source licenses and will be deposited with the HMP Data Analysis and Coordination Center (DACC). The investigators intend to work closely with other researchers involved in the HMP in order to ensure rapid progress. PUBLIC HEALTH RELEVANCE: Microbial communities associated with the human body play critical roles in human health and disease. This project will provide methods that help establish the nature and variability of microbial communities in healthy human individuals. Using these individuals as a baseline, this work will will pave the way for studies of a wide range of medical conditions that these communities affect by looking for abnormal communities associated with specific disease states, allowing the development of new diagnostics and therapeutic approaches.

描述（由申请人提供）：居住在人体中的微生物的数量级超过人类细胞，并影响健康和疾病的许多方面，包括肥胖，阴道病和克罗恩病。了解这种内源性菌群正在成为了解人类基因组和遗传变异对健康和疾病的作用的关键扩展。人类微生物组项目（HMP）将使用元基因组测序来表征大量个人健康人中的微生物群落。因此，迫切需要解释序列数据以了解微生物群落组成和动态的新方法。该项目将从生态学到进化生物学再到应用数学的学科团结，以通过评估微生物多样性和变化的度量以及创建所需的新的社区组成指标来开发新方法，以了解哪些身体栖息地或多或少相似。这将使您了解临床相关的参数（例如年龄，性别或特定人栖息地的pH值）如何影响这些社区，以及个人内部微生物群落的变化动态，个人之间的传播以及人类与环境之间的传播。该项目直接响应Roadmap RFA，以开发用于人类微生物组项目数据计算分析的新工具。该提案的具体目的是：目标1。发展，表征和应用微生物社区多样性的丰富描述符。目标2。开发描述人类微生物群落如何随时间和空间变化的方法。目标3。开发新方法来追踪不同社区之间生物的流动。拟议工作的一些关键方面是：开发用于估计人栖息地中微生物多样性的新统计方法；开发描述微生物社区多样性的丰富方法；通过大规模模拟和使用以经验表征微生物群落的最大可用数据集，详尽地验证了用于比较微生物群落的方法；并开发了追踪使用标记基因和全元素数据居住在人体的微生物来源的新方法。关键结果包括帮助确定人类微生物组核心的程度，以及如何最好地采样人类微生物多样性。所有开发的方法将根据开源许可提供，并将通过HMP数据分析和协调中心（DACC）存放。研究人员打算与参与HMP的其他研究人员紧密合作，以确保快速进步。公共卫生相关性：与人体相关的微生物群落在人类健康和疾病中起关键作用。该项目将提供有助于确定健康人类中微生物群落的性质和变异性的方法。将这些人用作基准，这项工作将为研究各种医疗状况的研究铺平道路，这些社区通过寻找与特定疾病状态相关的异常社区来影响这些状况，从而允许开发新的诊断和治疗方法。