Exploring the Niche Space of Human Microbiome Functions through Convex Geometry and Evolutionary Genomics
通过凸几何和进化基因组学探索人类微生物组功能的利基空间
基本信息
- 批准号:1069303
- 负责人:
- 金额:$ 150.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-08-15 至 2016-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The human microbiome is the vast collection of microorganisms living in and on our bodies. While researchers are only just beginning to understand the complex roles that these microbes play in human biology, it is clear that specific changes in microbial flora are associated with and sometimes cause or cure disease in the host. Most microbiome research to date has focused on describing the taxonomic composition of communities in different body sites (e.g., gut, mouth, elbow skin) or in a single site across disease groups. The goal of this project is to move microbiome research from descriptions of "who is out there?" towards characterizations of "what they are doing?". To do so the investigators will develop new methodology for analyzing shotgun metagenomic data, which is a pooled sample of DNA extracted and sequenced from the various microbes in a community. Because the sequences represent short segments of the genomes of many organisms, metagenomics provides a snapshot of the protein repertoire of a microbiome community. This rich data holds great promise and also presents many challenges for data analysis. To meet these challenges, the investigators will first design and validate a bioinformatics pipeline to classify metagenomic sequences into protein families. The key component of this tool will be hidden Markov models describing the evolutionary profile of every known microbial protein, enabling accurate characterization of the protein functions present in a sample. Second, they will derive novel stochastic models to predict the occurrence of protein families in a metagenomic sample given data about the demographic and clinical characteristics of a patient. These models, based on concepts from ecology and convex geometry, will allow the investigators to estimate, draw, and statistically compare the shapes of protein niches in high-dimensional phenotype space. Finally, they will produce a medical Niche Atlas that will link protein distributions to disease states via a publicly accessible, user-friendly visualization tool and database. This project will produce new mathematical theory and novel computational tools for microbiome research, drug development, and bioprospecting. In addition to immediate impacts on microbiome research, our mathematical results will be useful for spatial modeling in other fields, such as ecology, sociology, and epidemiology.The aim of this project is to develop computational resources and stochastic models that will shed light on the complex relationship between the health of an individual and the activities of the microbes living in and on his/her body. This research will generate a medical Niche Atlas that will map the distributions of microbial protein functions across individuals with different clinical characteristics (e.g., diseases, diets, or treatments). Just as a geographic atlas makes cartographic expertise accessible to a layperson, our Niche Atlas will allow researchers, students, clinicians, and any curious person to easily explore the functional capabilities of the human microbiome from a computer terminal. Its protein niche maps will visually display the range of patient characteristics at which each microbial protein is likely to occur and how these ranges differ across disease states. We will leverage this capability as a graduate teaching tool, for outreach and communication through public media, and to establish experimental collaborations to test the hypotheses we generate about the roles of microbiome proteins in human diseases, such as inflammatory bowel disease. These investigations will aim to identify new disease biomarkers, including microbiome proteins that can be used to diagnose onset of disease in patient subpopulations where early diagnosis is currently difficult. The Niche Atlas will also enable development of personalized treatments and preventions based on knowledge of an individual?s microbiome. Together, these freely accessible resources will significantly broaden access to cutting-edge medicine.
人体微生物群是生活在我们体内和体表的大量微生物。虽然研究人员才刚刚开始了解这些微生物在人类生物学中的复杂作用,但很明显,微生物菌群的特定变化与宿主的疾病有关,有时会引起或治愈疾病。迄今为止,大多数微生物组研究都集中在描述不同身体部位(如肠道、口腔、肘部皮肤)或疾病组中单一部位的群落分类组成。该项目的目标是将微生物组研究从描述“谁在那里?”转向描述“他们在做什么?”。为此,研究人员将开发新的方法来分析散弹枪宏基因组数据,这是从一个群落中各种微生物中提取和测序的DNA样本。由于这些序列代表了许多生物体基因组的短片段,宏基因组学提供了微生物群落蛋白质库的快照。这些丰富的数据带来了巨大的希望,也给数据分析带来了许多挑战。为了应对这些挑战,研究人员将首先设计并验证一个生物信息学管道,将宏基因组序列分类为蛋白质家族。该工具的关键组成部分将是描述每种已知微生物蛋白质进化概况的隐马尔可夫模型,从而能够准确表征样品中存在的蛋白质功能。其次,他们将推导出新的随机模型来预测宏基因组样本中蛋白质家族的发生,并给出有关患者的人口统计学和临床特征的数据。这些基于生态学和凸几何概念的模型,将允许研究人员在高维表型空间中估计、绘制和统计比较蛋白质生态位的形状。最后,他们将制作一个医学生态位图谱,通过一个可公开访问的、用户友好的可视化工具和数据库,将蛋白质分布与疾病状态联系起来。该项目将为微生物组研究、药物开发和生物勘探提供新的数学理论和新的计算工具。除了对微生物组研究的直接影响外,我们的数学结果将对生态学、社会学和流行病学等其他领域的空间建模有用。该项目的目的是开发计算资源和随机模型,以揭示个人健康与生活在其体内和体表的微生物活动之间的复杂关系。这项研究将生成一个医学生态位图谱,绘制具有不同临床特征(如疾病、饮食或治疗)的个体之间微生物蛋白功能的分布。就像地理地图集可以让外行获得制图专业知识一样,我们的利基地图集将允许研究人员,学生,临床医生和任何好奇的人从计算机终端轻松探索人类微生物组的功能能力。它的蛋白质生态位图将直观地显示每种微生物蛋白质可能出现的患者特征范围,以及这些范围在不同疾病状态下的差异。我们将利用这一能力作为研究生教学工具,通过公共媒体进行外联和交流,并建立实验合作,以测试我们关于微生物组蛋白在人类疾病(如炎症性肠病)中的作用的假设。这些研究将旨在确定新的疾病生物标志物,包括微生物组蛋白,可用于诊断目前难以早期诊断的患者亚群中的疾病发病。小生境地图集还将使基于个人知识的个性化治疗和预防得以发展。微生物组。总之,这些免费获取的资源将大大扩大获得尖端药物的途径。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Katherine Pollard其他文献
Daytime melatonin administration in elderly good and poor sleepers: effects on core body temperature and sleep latency.
老年人睡眠质量好和差的白天服用褪黑激素:对核心体温和睡眠潜伏期的影响。
- DOI:
- 发表时间:
1997 - 期刊:
- 影响因子:5.6
- 作者:
K. Lushington;Katherine Pollard;Leon C. Lack;D. Kennaway;Drew Dawson - 通讯作者:
Drew Dawson
An integrated approach for individualised support: carers' views
个性化支持的综合方法:护理人员的观点
- DOI:
10.1108/jica-09-2014-0034 - 发表时间:
2014 - 期刊:
- 影响因子:0.8
- 作者:
P. Moule;Katherine Pollard;J. Clarke;C. Fear;Bob Lawson;R. Thompson;P. Young - 通讯作者:
P. Young
Men affected by prostate cancer: a survey of general practitioners’ learning needs
受前列腺癌影响的男性:全科医生学习需求调查
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:1.3
- 作者:
P. Moule;Emma Gibbard;Katherine Pollard - 通讯作者:
Katherine Pollard
Supervised Self-Collected SARS-Cov-2 Testing in Classroom-Based Summer Camps to Inform Safe In-Person Learning
在课堂夏令营中监督自我收集的 SARS-Cov-2 测试,为安全的面对面学习提供信息
- DOI:
10.26502/jppch.74050065 - 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
Peter B Cooch;Anna;Apryl Olarte;E. Crawford;J. Derisi;B. Greenhouse;J. Hakim;K. Turcios;Katherine Pollard;Lee R. Atkinson;R. Hirsch;R. Keller;T. Ruel;Auritte Cohen;Araceli Leon;Naomi S. Bardach - 通讯作者:
Naomi S. Bardach
The University of the West of England
西英格兰大学
- DOI:
10.1007/978-1-349-94186-5_1222 - 发表时间:
2014 - 期刊:
- 影响因子:3.2
- 作者:
Katherine Pollard;I. Fletcher;H. Martin;M. Hughes - 通讯作者:
M. Hughes
Katherine Pollard的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Katherine Pollard', 18)}}的其他基金
Decoding Strain-Level Variation in the Human Microbiome
解码人类微生物组的菌株水平变异
- 批准号:
1563159 - 财政年份:2016
- 资助金额:
$ 150.85万 - 项目类别:
Continuing Grant
相似国自然基金
SDF-1调控椎间盘区域干细胞niche内干细胞内源性修复的作用及机制研究
- 批准号:MS25H060031
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
色氨酸代谢重编程通过GPR35重塑肠道干细胞Niche驱动受损肠黏膜再生修复的分子机制
- 批准号:
- 批准年份:2024
- 资助金额:30.0 万元
- 项目类别:省市级项目
CD84+单核巨噬细胞招募至肺组织形成niche促进SSc-ILD进展
- 批准号:82370073
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
miR-106b-5p调控增殖niche中肝脏细胞间时空互作介导川楝素肝损伤的适应性反应机制研究
- 批准号:82374136
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
T细胞通过骨髓niche途径致骨髓cGVHD中纤维化的机制研究
- 批准号:82300241
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
苓桂术甘汤联合肝癌干细胞niche多策略靶向递送系统防-治原发性肝癌的机制研究
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
血管niche中的Hippo信号通路通过调控内皮衰老分泌表型促进组织微环境的病理变化及其机制研究
- 批准号:
- 批准年份:2021
- 资助金额:58 万元
- 项目类别:面上项目
基于调控星形胶质细胞介导的谷氨酸—谷氨酰胺循环改善海马niche探讨楮实子促神经发生治疗AD的作用及机制
- 批准号:82104422
- 批准年份:2021
- 资助金额:24.00 万元
- 项目类别:青年科学基金项目
基于调控星形胶质细胞介导的谷氨酸-谷氨酰胺循环改善海马niche探讨楮实子促神经发生治疗AD的作用及机制
- 批准号:
- 批准年份:2021
- 资助金额:30 万元
- 项目类别:
自愿运动改善niche信号调控内源性NSCs行为促进脑损伤修复的作用及机制
- 批准号:
- 批准年份:2021
- 资助金额:55 万元
- 项目类别:面上项目
相似海外基金
CAREER: Hybridization and radiation: Integrating across phylogenomics, ancestral niche evolution, and pollination biology
职业:杂交和辐射:系统基因组学、祖先生态位进化和授粉生物学的整合
- 批准号:
2337784 - 财政年份:2024
- 资助金额:
$ 150.85万 - 项目类别:
Continuing Grant
海馬neurogenic nicheの環境整備とダイレクトリプログラミングによる認知機能再生
通过创建海马神经源性生态位环境和直接重编程实现认知功能再生
- 批准号:
24K14748 - 财政年份:2024
- 资助金额:
$ 150.85万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Engineering the bone marrow niche to control stem cell regulation, metastatic evolution and cancer dormancy
改造骨髓生态位来控制干细胞调节、转移进化和癌症休眠
- 批准号:
EP/X036049/1 - 财政年份:2024
- 资助金额:
$ 150.85万 - 项目类别:
Research Grant
Mechanistic niche predictive modelling of plant invasion at the range front
山脉前沿植物入侵的机械生态位预测模型
- 批准号:
EP/Y028473/1 - 财政年份:2024
- 资助金额:
$ 150.85万 - 项目类别:
Fellowship
Identification of factor to induce lactic acidosis in pre-metastatic niche
转移前微环境中诱导乳酸性酸中毒的因素的鉴定
- 批准号:
23K06620 - 财政年份:2023
- 资助金额:
$ 150.85万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Stem cell/niche biomechanics in intestinal health and disease
肠道健康和疾病中的干细胞/利基生物力学
- 批准号:
2885708 - 财政年份:2023
- 资助金额:
$ 150.85万 - 项目类别:
Studentship
Modulation of the biliary immune niche by the microbiome
微生物组对胆道免疫生态位的调节
- 批准号:
10349405 - 财政年份:2023
- 资助金额:
$ 150.85万 - 项目类别:
Epigenetically regulated stemness program and stem cell niche as targets in pediatric DIPG
表观遗传调控的干细胞程序和干细胞生态位作为儿科 DIPG 的目标
- 批准号:
10635435 - 财政年份:2023
- 资助金额:
$ 150.85万 - 项目类别:
Regulation and function of aged hematopoietic stem cell (HSC) niche
衰老造血干细胞(HSC)生态位的调节和功能
- 批准号:
10723396 - 财政年份:2023
- 资助金额:
$ 150.85万 - 项目类别:
Selective Radionuclide Delivery for Precise Bone Marrow Niche Alterations
选择性放射性核素输送以实现精确的骨髓生态位改变
- 批准号:
10727237 - 财政年份:2023
- 资助金额:
$ 150.85万 - 项目类别: