Genome Variability and Population Processes of Lyme Disease Pathogens

莱姆病病原体的基因组变异和群体过程

• 批准号: 8810213
• 负责人: WEIGANG QIU
• 金额: $ 26.78万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-06 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8810213
• 关键词: Age; Amino Acid Sequence; Bacterial Genome; Bioinformatics; Borrelia; Borrelia burgdorferi; Borrelia burgdorferi Group; Candidate Disease Gene; Chromosomes; Clinical; Collaborations; Communicable Diseases; Complex; Computer Simulation; Computer software; Data; Dentistry; Development; Diagnostic; Disease; Disease Outbreaks; Ecology; Emerging Communicable Diseases; Epidemiology; Escherichia coli; Europe; Evolution; Funding; Gene Duplication; Gene Family; Genes; Genetic Recombination; Genome; Genomics; Germany; Goals; Habitats; Health; Human; Immune; Incidence; Individual; Informatics; Ixodes; Letters; Lyme Disease; Maryland; Medicine; Methods; Modeling; Molecular; Monitor; Natural Selections; Nature; New Jersey; North America; Order Spirochaetales; OspC protein; Outcome; Pattern; Phylogenetic Analysis; Phylogeny; Physicians; Plasmids; Play; Population; Population Process; Population Size and Growth; Recording of previous events; Regulatory Element; Research; Research Infrastructure; Research Personnel; Research Proposals; Resistance; Role; Route; Sequence Analysis; Software Tools; Structure; Sum; Surface Antigens; Technology; Testing; Ticks; Time; Universities; Utah; Vector-transmitted infectious disease; Virulence; Virulence Factors; base; climate change; comparative; comparative genomics; computer based statistical methods; deep sequencing; emerging infectious disease evolution; genome database; genome sequencing; genome-wide; genomic variation; innovation; meetings; novel strategies; novel vaccines; open source; pathogen; predictive modeling; programs; public health research; repository; simulation; tool; transmission process

DESCRIPTION (provided by applicant): Evolutionary genomics is a key to controlling emerging infectious diseases by identifying virulence genes in the pathogen genome and by revealing patterns and mechanisms of disease spread. Lyme disease, caused by pathogens belonging to the bacterial species complex Borrelia burgdorferi sensu lato, is the most common vector-borne disease in North America and Europe. Although geographically limited, the Lyme disease endemic has greatly expanded in range in recent decades with little predictability. In the past four years, the PI and his collaborators have sequenced the genomes of twenty-three world-wide representative strains of Lyme disease pathogens. Along with the half dozen genomes previously sequenced by this and other research groups, this large amount of Borrelia genomes usher in a new era of understanding the genomic and ecological basis of Lyme disease endemics through evolutionary and comparative genomics. The SC3 support during 1998- 2012 is behind the PI's leading roles in the phylogeny-based selection of strains for whole-genome sequencing, the discovery of widespread recombination and estimation of its rates, and the development of a computational model of B. burgdorferi genome diversity driven by immune escape at a few major surface antigen loci and the outer-surface protein C (ospC) locus in particular. In addition, the SC3 projects resulted in a mature bioinformatics and analytical infrastructure in the PI's lab including, e.g., a customized genome database, a suite of Perl/BioPerl based software tools ("DNATweezers"), and a simulator of bacterial genome evolution ("SimBac"). The latter two tools have been released into public repository SourceForge.net as Open Source projects. The PI's specific aims for the proposed SC1 project are to (i) reveal genome variability associated with B. burgdorferi virulence by tests of positive and purifying natural selection, (ii) launch a new line of research in the phylodynamics of Borrelia for predicting the spread of Lyme endemics, and (iii) modernize comparative genomics studies of pathogens by develop evolutionary bioinformatics tools. The PI will develop non-SCORE research proposals through widening collaboration with Borrelia molecular geneticists and Lyme ecologists and developing translational and innovative research programs in population genomics of Lyme disease. To summarize, the overall goal and expected outcomes of the project will be an elucidation of virulence-associated genomic variations, predictive models of the spread of Lyme disease endemics, and a nationally competitive research program in ecology and evolution of emerging infectious diseases. The project helps to control the spread of Lyme disease by identifying virulence genes and by predicting pathogen spread in nature.

描述（由申请人提供）：进化基因组学是通过识别病原体基因组中的毒力基因并揭示疾病传播的模式和机制来控制新出现的传染病的关键。莱姆病是由属于伯氏疏螺旋体细菌复合体的病原体引起的，是北美和欧洲最常见的媒介传播疾病。尽管地域有限，但莱姆病的流行范围在近几十年来已大大扩大，而且几乎无法预测。在过去的四年里，首席研究员和他的合作者对全球 23 种莱姆病病原体代表性菌株的基因组进行了测序。与该研究小组和其他研究小组先前测序的六个基因组一起，大量的疏螺旋体基因组开创了通过进化和比较基因组学了解莱姆病地方病的基因组和生态基础的新时代。 1998 年至 2012 年间的 SC3 支持使得 PI 在基于系统发育的全基因组测序菌株选择、广泛重组的发现及其速率估计以及伯氏疏螺旋体基因组计算模型的开发方面发挥了主导作用。一些主要表面抗原基因座，特别是外表面蛋白 C (ospC) 基因座的免疫逃逸驱动了多样性。此外，SC3 项目在 PI 实验室中建立了成熟的生物信息学和分析基础设施，包括定制的基因组数据库、一套 基于 Perl/BioPerl 的软件工具（“DNATweezers”）和细菌基因组进化模拟器（“SimBac”）。后两个工具已作为开源项目发布到公共存储库 SourceForge.net 中。 PI 提议的 SC1 项目的具体目标是 (i) 通过阳性和纯化自然选择测试揭示与伯氏疏螺旋体毒力相关的基因组变异，(ii) 启动伯氏疏螺旋体系统动力学的新研究系列，以预测其传播莱姆病流行病的研究，以及（iii）通过开发进化生物信息学工具使病原体的比较基因组学研究现代化。 PI 将通过扩大与疏螺旋体分子遗传学家和莱姆病生态学家的合作来制定非 SCORE 研究计划，并开发莱姆病群体基因组学的转化和创新研究项目。总而言之，该项目的总体目标和预期成果将是阐明毒力相关的基因组变异、莱姆病流行病传播的预测模型，以及在新兴传染病的生态和进化方面具有全国竞争力的研究计划。该项目通过识别毒力基因和预测病原体在自然界的传播来帮助控制莱姆病的传播。