Ecology of Cystic Fibrosis: Administrative Supplement

囊性纤维化的生态学：行政补充

基本信息

批准号：
8637669
负责人：
FOREST L ROHWER
金额：
$ 4.85万
依托单位：
SAN DIEGO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-12-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8637669
关键词：
Administrative Supplement Aftercare Antibiotic Therapy Antimicrobial susceptibility Chemicals Clinical Communities Complex Computing Methodologies Cystic Fibrosis Data Data Analyses Databases Detection Development Disease Early Intervention Ecology Flare Future Goals Health Human Imagery Infection Intravenous Knowledge Lung Maps Mass Spectrum Analysis Methodology Methods Microbe Microbiology Molecular Molecular Analysis Monitor Nature Outcome Parents Patients Pattern Pulmonary Cystic Fibrosis Research Research Project Grants Sampling Sputum Staging Structure System Testing Time base biosignature clinically relevant cystic fibrosis patients early cystic fibrosis human disease innovation interest metabolomics microbial microbial community novel novel strategies parent grant pathogen therapy development treatment strategy two-dimensional

项目摘要

The metabolomics of cystic fibrosis (CF) is virtually unexplored. There is an urgent need to understand the dynamics of the CF microbial community and which microbes are active during particular disease states. Metabolomics can reveal the chemical compounds produced by active microbes in the CF lung and provide a new approach for analysis of this complex microbial community. However, the complexity of CF sputum makes traditional metabolomics and mass spectrometry (MS) data analysis methods unfeasible. The Dorrestein lab at UCSD has developed computational methods to compare mass spectra of parent metabolite fragmentation patterns produced by microbial cultures. The similarity between molecules is revealed in their fragmentation patterns in MS and these similarities can be visualized in a 2-dimensional network called a ¿molecular network¿. This study will expand the molecular networking methods of the Dorrestein lab to a complex polymicrobial sample from a human disease. We aim to monitor CF patients through the course of a cystic fibrosis pulmonary exacerbation (CFPE) and highlight metabolites and related clusters of molecules specific to certain states of disease. In addition, we aim to determine how the metabolome of a sputum sample is different between patients that respond to CFPE treatment and those who don¿t. This study will apply a novel innovation to molecular networking by seeding CF sputum networks with MS data from cultured CF pathogens. This will allow visualization of the action of particular pathogens in sputum at time of sampling. This methodology will revolutionize the field of metabolomics and can be applied to human and environmental samples containing complex microbial communities. Fulfillment of this project¿s specific aims will provide new information about the dynamics of CF infections. Identification of metabolites produced by active microbes during CFPE development and which microbes remain active during an ineffective treatment will aid doctors in employing more targeted therapies to a patient¿s CFPE. This supplemental research project will produce metabolomes from CF sputum and bacterial pathogens containing thousands of molecules and molecular networks that visualizes the relationships of these molecules. This will allow a basis for developing more informative and productive databases for metabolomics that have lagged behind analogous sequence databases.

囊性纤维化（CF）的代谢组学实际上是出乎意料的。迫切需要了解CF微生物群落的动态以及在特定疾病状态下哪些微生物活跃。代谢组学可以揭示CF肺中活性微生物产生的化合物，并为分析这种复杂的微生物群落提供了新的方法。但是，CF痰的复杂性使传统的代谢组学和质谱法（MS）数据分析方法不可行。 UCSD的Dorrestein Lab开发了计算方法，以比较微生物培养物产生的父代谢产物片段化模式的质谱。分子之间的相似性在其MS中的碎裂模式中揭示了，这些相似性可以在一个称为A分子网络的二维网络中可视化。这项研究将将Dorrestein Lab的分子网络方法扩展到人类疾病中复杂的多生物样品。我们旨在通过囊性纤维化肺部加重（CFPE）监测CF患者，并突出特定于某些疾病状态的分子的代谢产物和相关簇。此外，我们旨在确定对CFPE治疗反应的患者与不thos的患者之间的代谢组有何不同。这项研究将通过将CF痰网络用培养的CF病原体的MS数据播种，将新的创新应用于分子网络。这将允许在抽样时在痰液中特定病原体的作用可视化。该方法将彻底改变代谢组学领域，并可以应用于包含复杂微生物群落的人类和环境样本。实现该项目的特定目标将提供有关CF感染动态的新信息。在CFPE发育过程中，活性微生物产生的代谢产物以及在无效治疗期间保持活跃的代谢物将有助于医生对患者使用更多靶向疗法。该补充研究项目将产生来自CF痰的代谢组和包含数千个分子和分子网络的细菌病原体，可视化这些分子的关系。这将允许为落后于类似序列数据库的代谢组学开发更多信息和生产性数据库的基础。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A genomic perspective on a new bacterial genus and species from the Alcaligenaceae family, Basilea psittacipulmonis.

DOI：
10.1186/1471-2164-15-169
发表时间：
2014-03-01
期刊：
BMC genomics
影响因子：
4.4
作者：
Whiteson KL;Hernandez D;Lazarevic V;Gaia N;Farinelli L;François P;Pilo P;Frey J;Schrenzel J
通讯作者：
Schrenzel J

Purifying the impure: sequencing metagenomes and metatranscriptomes from complex animal-associated samples.

纯化不纯物：对复杂动物相关样本中的宏基因组和宏转录组进行测序。

DOI：
10.3791/52117
发表时间：
2014
期刊：
Journal of visualized experiments : JoVE
影响因子：
0
作者：
Lim,YanWei;Haynes,Matthew;Furlan,Mike;Robertson,CharlesE;Harris,JKirk;Rohwer,Forest
通讯作者：
Rohwer,Forest

Microbial, host and xenobiotic diversity in the cystic fibrosis sputum metabolome.