A method for the culture-free discovery and host affiliation of novel viruses from metagenomic samples

一种从宏基因组样本中无需培养地发现新型病毒并确定其宿主归属的方法

• 批准号: 10347377
• 负责人: Ivan Liachko
• 金额: $ 82.04万
• 依托单位: PHASE GENOMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-08 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10347377
• 关键词: Affect; Antimicrobial Resistance; Bacteria; Bacteriophages; Biology; Biotechnology; Cells; Chemistry; Communicable Diseases; Communities; Complex; Computer software; Computing Methodologies; Consumption; DNA; DNA Sequence; Data; Data Analyses; Development; Disease; Ecosystem; Feces; Genome; Genomics; Health; Hi-C; Horizontal Gene Transfer; Human; Human Microbiome; Internet; Libraries; Ligation; Lytic; Measurement; Metabolism; Metagenomics; Methodology; Methods; Microbe; Microbiology; Online Systems; Outcome; Phase; Planets; Play; Population; Predatory Behavior; Preparation; Reagent; Recovery; Reporting; Research; Resistance to infection; Retinal blind spot; Role; Safety; Sampling; Satellite Viruses; Series; Shapes; Site; Technology; Therapeutic; Time; Viral; Viral Genome; Virus; Virus-like particle; Visualization; Work; base; computational platform; contig; crosslink; data quality; experimental study; fecal transplantation; genome analysis; improved; in vivo; interest; metagenome; microbial; microbial community; microbial host; microbiome; microorganism; next generation sequencing; novel; novel strategies; novel virus; particle; public database; resistance gene; restriction enzyme; tool; transmission process; user-friendly; vector; web portal; web-based tool

ABSTRACT In this application, we propose to develop a novel reagent kit and accompanying analytic software platform that employs Hi-C technology for a user-friendly method to assemble viral genomes from metagenomic samples and associate these viruses with their microbial hosts. This product enables culture-free discovery of phages and quantitative measurement of their host range directly in mixed microbial communities. Bacteriophages are viruses that infect bacteria; they shape microbial ecosystems through predation on hosts and through horizontal gene transfer. They are also an important vector in the transmission of anti-microbial resistance. Despite their potent impact on microbial biology, only a tiny proportion of phage genomes are represented in public databases in part because of the difficulty of isolating phage whose hosts are not culturable laboratory settings. This limitation in our ability to understand viral biology has important impacts on emerging biotechnology applications including fecal microbiota transplantation and phage therapy as well as wide-ranging effects on microbiological research. We propose to develop a novel computational approach combined with improved experimental methods to deconvolute viral genomes and perform host attribution from whole microbiome samples without culturing. At the core of this approach is utilization of proximity ligation methods (Hi-C) which physically associates DNA sequences present within intact microbes. This provides direct physical evidence of the contiguity of viral genome sequences and host affiliation information that is not achievable by any other method. The outcome of this direct-to-Phase II proposal would be a combination of kit and user-facing computational platform that would empower both the sophisticated next-generation-sequencing biologist and the sequencing novice to ask important questions about viruses in their microbial community of interest. Aim 1 focuses on computational methods improve the recovery of viral genomes from metagenomic data. Aim 2 develops methodologies to enhance viral Hi-C chemistry. These two aims work together synergistically enhance data quality. Finally, Aim 3 develops a computational platform for data analysis through a web portal where results could be visualized directly via web browser or raw data downloaded for further exploration. Upon completion we will have developed a first-in-class commercial platform to discover viral genomes and identify their hosts from complex microbial communities.

抽象的 在此应用中，我们建议开发一种新型试剂盒和随附的分析软件平台， 采用 Hi-C 技术提供一种用户友好的方法，从宏基因组样本中组装病毒基因组， 将这些病毒与其微生物宿主联系起来。该产品能够实现噬菌体的无培养发现 直接在混合微生物群落中定量测量其宿主范围。 噬菌体是感染细菌的病毒；它们通过捕食宿主来塑造微生物生态系统 并通过水平基因转移。它们也是传播抗菌药物的重要载体 反抗。尽管它们对微生物生物学具有强大的影响，但只有一小部分噬菌体基因组被 出现在公共数据库中的部分原因是难以分离宿主不可培养的噬菌体 实验室设置。我们理解病毒生物学能力的这种限制对新兴病毒产生了重要影响 生物技术应用，包括粪便微生物群移植和噬菌体治疗以及广泛的 对微生物研究的影响 我们建议开发一种新颖的计算方法与改进的实验方法相结合 对病毒基因组进行解卷积，并在无需培养的情况下从整个微生物组样本中进行宿主归因。在 该方法的核心是利用邻近连接方法 (Hi-C) 将 DNA 物理连接起来 存在于完整微生物中的序列。这提供了病毒连续性的直接物理证据 任何其他方法都无法获得的基因组序列和宿主隶属关系信息。 这个直接进入第二阶段提案的结果将是套件和面向用户的计算的组合 该平台将为复杂的下一代测序生物学家和测序人员提供支持 新手可以提出有关其感兴趣的微生物群落中的病毒的重要问题。目标 1 侧重于 计算方法提高了从宏基因组数据中恢复病毒基因组的能力。目标 2 制定 增强病毒 Hi-C 化学的方法。这两个目标共同作用，协同增强数据 质量。最后，Aim 3 开发了一个计算平台，通过门户网站进行数据分析，其中结果 可以通过网络浏览器直接可视化或下载原始数据以进行进一步探索。完成后 我们将开发一个一流的商业平台来发现病毒基因组并识别其宿主 来自复杂的微生物群落。

项目成果

Litter Commensal Bacteria Can Limit the Horizontal Gene Transfer of Antimicrobial Resistance to Salmonella in Chickens.

窝共生细菌可以限制鸡体内沙门氏菌抗菌素耐药性的水平基因转移。

• 发表时间: 2022-05-10
• 影响因子: 4.4
• 作者: Oladeinde, Adelumola;Abdo, Zaid;Zwirzitz, Benjamin;Woyda, Reed;Lakin, Steven M;Press, Maximilian O;Cox, Nelson A;Thomas 4th, Jesse C;Looft, Torey;Rothrock Jr, Michael J;Zock, Gregory;Plumblee Lawrence, Jodie;Cudnik, Denice;Ritz, Casey;Aggrey
• 通讯作者: Aggrey

Generating lineage-resolved, complete metagenome-assembled genomes from complex microbial communities.

从复杂的微生物群落中生成谱系解析的、完整的宏基因组组装的基因组。

• 发表时间: 2022-05
• 影响因子: 46.9
• 作者: Bickhart, Derek M;Kolmogorov, Mikhail;Tseng, Elizabeth;Portik, Daniel M;Korobeynikov, Anton;Tolstoganov, Ivan;Uritskiy, Gherman;Liachko, Ivan;Sullivan, Shawn T;Shin, Sung Bong;Zorea, Alvah;Andreu, Victòria Pascal;Panke;Medema, M
• 通讯作者: Medema, M

Integrating chromatin conformation information in a self-supervised learning model improves metagenome binning.

将染色质构象信息整合到自我监督学习模型中可以改善宏基因组分箱。

• 发表时间: 2023
• 影响因子: 2.7
• 作者: Ho, Harrison;Chovatia, Mansi;Egan, Rob;He, Guifen;Yoshinaga, Yuko;Liachko, Ivan;O'Malley, Ronan;Wang, Zhong
• 通讯作者: Wang, Zhong