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（申请人提供）：进化基因组学是通过鉴定病原体基因组中的毒力基因并揭示疾病扩散的模式和机制来控制新兴传染病的关键。莱姆病是由属于细菌物种复合物的病原体引起的，是北美和欧洲最常见的媒介传播疾病。尽管在地理位置上有限，但莱姆病流行的近几十年来范围内却大大扩展，几乎没有可预测性。在过去的四年中，PI和他的合作者对莱姆病病原体的二十三个代表性菌株进行了测序。除了先前由该研究组和其他研究小组对六个基因组进行测序的六个基因组外，这种大量的伯氏基因组在一个新的时代，即通过进化和比较基因组学了解莱姆病特征的基因组和生态基础。 1998年至2012年的SC3支持是PI在基于系统发育的菌株选择中的主要作用，用于全基因组测序，发现广泛的重组和速率的估计以及B. burgdorferi B. burgdorferi基因组多样性的计算模型的发展，由免疫表面抗原抗原位置和外部抗原位置驱动，外观和外观蛋白质（Opts and syserface）（均为外观）。此外，SC3项目在PI实验室中导致了成熟的生物信息学和分析基础架构，包括，例如，一个定制的基因组数据库，一套 基于Perl/Bioperl的软件工具（“ DNATWEEZERS”），以及细菌基因组进化的模拟器（“ Simbac”）。后两个工具已被释放到公共存储库SourceForge.net中，作为开源项目。 PI针对拟议的SC1项目的具体目的是（i）通过测试正面和净化自然选择的测试来揭示与B. burgdorferi毒力相关的基因组变异性，（ii）在伯雷利亚的系统动力学方面启动了一系列新的研究系列，以预测莱姆斯的传播工具，以及（iii）现代化的基因组生物学研究，以预测lyme genomics的传播。 PI将通过扩大与疏螺旋体分子遗传学家和莱姆生态学家的合作，并在莱姆病的人群基因组中开发转化和创新研究计划，从而制定非分数研究建议。总而言之，该项目的总体目标和预期结果将是阐明与毒力相关的基因组变异，莱姆病疾病的传播的预测模型，以及一项全国竞争性感染性疾病的生态和进化方面的竞争性研究计划。该项目通过鉴定毒力基因并预测自然病原体传播来帮助控制莱姆病的传播。