Statistical pangenomics to study the effects of zoonotic exposure on the gut microbiome

统计泛基因组学研究人畜共患病暴露对肠道微生物组的影响

• 批准号: 10428940
• 负责人: Amy D Willis
• 金额: $ 23.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-25 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428940
• 关键词: Address; Algorithms; Amino Acids; Animals; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Bacteria; Bacterial Antibiotic Resistance; Bacterial Genome; Bacterial Model; Communicable Diseases; Communities; Computer software; Data; Disease; Ecology; Emerging Communicable Diseases; Evolution; Experimental Designs; Exposure to; Farm; Farming environment; Genes; Genome; Genomics; Guidelines; Human; Human Microbiome; Infection; Light; Livestock; Metabolic Pathway; Metagenomics; Methodology; Methods; Modeling; Pathogenicity; Persons; Population; Procedures; Public Health; Publishing; Resistance; Resolution; Risk; Shotgun Sequencing; Shotguns; Single Nucleotide Polymorphism; Statistical Methods; Statistical Models; Testing; Variant; Virulence; Work; Zoonoses; bacterial community; bacterial resistance; base; cohort; design; disorder prevention; experimental study; gut microbiome; high risk; improved; infection risk; insight; metagenome; metagenomic sequencing; microbial; microbial genome; microbiome; microbiome research; novel; open source; pathogen; pathogen spillover; pressure; response; transmission process

Project Summary: Zoonotic diseases result from the spillover of pathogens from animal reservoirs to humans due to contact with animals or animal products. An estimated 60% of known infectious diseases and up to 75% of emerging infectious diseases are zoonotic in origin. Despite this, relatively little is known about the alterations to the human microbiome in persons with a high degree of close contact with animals on farms. We propose a study to understand the pathogenic and non- pathogenic effects of a high degree of livestock exposure. We will use shotgun metagenomics to investigate which bacteria colonize the human gut after zoonotic exposure, which bacteria are outcompeted by colonizers, and which bacteria adapt. To enable comparisons with respect to virulence, beneficial metabolic pathways and antibiotic resistance, we will develop novel statistical methods for bacterial pangenomics. Existing methods for bacterial pangenomics assume that all genomes are observed without error, which rarely is the case for metagenome- assembled genomes (MAGs). For example, MAGs may omit genes that are truly present in the target genome, or MAGs may contain erroneously observed genes. To address limitations of current methods, we will develop statistical methodology that adjusts for differential quality in gene-level comparisons of metagenome-assembled genomes. Additionally, we will develop guidelines for the design of shotgun sequencing experiments based on maximizing power to test hypotheses about associations with gene presence. Successful completion of these aims will increase our understanding of the mechanisms of transmission of zoonotic pathogens and commensals, and advance broadly applicable and essential methodology for comparing bacterial genomes.

项目摘要： 人畜共动性疾病是由于病原体从动物水库到人类的溢出而引起的 接触动物或动物产品。估计有60％的已知传染病和 多达75％的新兴传染病起源是人畜共患病。尽管如此，相对较少的是 知道对人类微生物组的变化，高度关闭的人 与农场上的动物接触。我们提出了一项研究，以了解致病性和非 - 高度牲畜暴露的致病作用。我们将使用shot弹枪宏基因组学 为了研究哪种细菌在人畜共患病后将人类肠道定居，哪种细菌是 被殖民者胜过，哪些细菌适应。为了比较 毒力，有益的代谢途径和抗生素耐药性，我们将发展新颖 细菌性pangenomics的统计方法。现有的细菌pangenomics方法 假设所有基因组都是没有误差的，元基因组很少发生这种情况 组装基因组（MAGS）。例如，MAG可能会省略真正存在的基因 靶基因组或MAG可能包含错误观察到的基因。解决限制 当前方法，我们将开发统计方法，以调整 元基因组组装基因组的基因级比较。此外，我们将发展 shot弹枪测序实验的设计指南，基于最大功能 测试有关与基因存在关联的假设。这些目标成功完成 将提高我们对人畜共患病原体传播机制的理解和 共生，并推进广泛适用的基本方法来比较 细菌基因组。