Enriching MGnify Genomes to capture the full spectrum of the microbiota and bolster taxonomic classifications

丰富 MGnify 基因组以捕获微生物群的全谱并支持分类学分类

• 批准号: BB/V01868X/1
• 负责人: Robert Finn
• 金额: $ 118.4万
• 依托单位: European Bioinformatics Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV01868X%2F1
• 关键词: Enriching; MGnify; Genomes; capture; full

Microbes (viruses, bacterial and single celled eukaryotes) are ubiquitous in nature and perform key roles essential to sustain life, e.g. oxygenation of the planet by marine microbes, soil nutrient cycling to support plant growth or facilitating animal digestion, especially human. Increasing knowledge about microbial ecosystems has accompanied a broadening scope of environments analysed, such as anaerobic digesters, food production systems and the built environment (extending as far as the International Space Station). Metagenomics is a culture independent method that applies modern DNA sequencing technologies to study the genomes of the organisms present in a microbiome. The latest approaches combine advanced sequencing technologies, throughput, and bioinformatics techniques to enable the assembly of short DNA fragments (produced by sequencing machines) into larger chromosomal fragments. Subsequently, these fragments are classified into sets belonging to an individual species, i.e. metagenome assembled genomes (MAGs). While the first MAG was reported in 2004, the first large-scale study applying these techniques was published only in 2015. Since then, there has been an explosion in the number of MAGs reported, which not only provides novel insights into the ~99% of organisms yet to be experimentally cultured but also dramatically expands the Tree of Life. In addition to capturing biodiversity of microbes, these MAGs facilitate a genome centric understanding of their functional role within the community, and how they interact with each other and their surroundings. A substantive section of applied research leverages these findings to restore perturbed microbiomes to a healthy state or to harness the enzymes they encode.This proposal focuses on MGnify, a resource that already performs four major roles in microbial community research: (i) it facilitates the capture of petabytes of sequence data being generated currently; (ii) it provides users access to the computational resources to conduct metagenomic assembly; (iii) it generates new knowledge by analysing microbiome derived sequence data and presenting this via a website and API to the user community; (iv) it has initiated capture of prokaryotic MAGs. In this proposal, we will extend MGnify to recover Eukaryotic MAGs using innovative new methodologies and capture the viruses in the MGnify assemblies. These non-redundant catalogues of Eukaryotic and viral genomes will be used to supplement the existing MGnify genomes. To perfect the MAG generation process, we propose to develop additional pipelines that will identify and remove the contaminants found in the prokaryotic MAGs. In addition to generating high-quality MAGs that cover the entire range of microbial taxa, we will harmonise efforts with the Genome Taxonomy Database (GTDB) to ensure that this newly discovered bacterial diversity is properly represented therein, as it is one of the most widely used resources for taxonomic classification. Underpinning this, we will enhance the metagenomic sequence submission systems to better cater for all data types and improve the internal mechanisms for data exchange, so that MGnify can perform submission on behalf of the users and gain access to all data types, whether the data is public or private (prepublication), given the appropriate user consent. Finally, in addition to updating the reference databases in our analysis pipelines, we will also improve the annotation of carbohydrate metabolism enzymes, which are poorly represented in databases currently.Collectively, these developments will reinforce MGnify's crucial importance to the microbiome research community. It will serve as the foundational knowledgebase that propels integrative microbiome research and its translation to real world applications.

微生物（病毒、细菌和单细胞真核生物）在自然界中无处不在，对维持生命起着至关重要的作用，例如，海洋微生物对地球的氧化作用，土壤养分循环以支持植物生长或促进动物消化，特别是人类消化。随着对微生物生态系统知识的增加，分析的环境范围也在扩大，例如厌氧消化器、食品生产系统和建筑环境（一直延伸到国际空间站）。宏基因组学是一种独立于培养的方法，它应用现代DNA测序技术来研究微生物组中存在的生物体的基因组。最新的方法结合了先进的测序技术、通量和生物信息学技术，使短DNA片段（由测序机产生）组装成更大的染色体片段成为可能。随后，这些片段被分类为属于单个物种的集合，即宏基因组组装基因组（MAGs）。虽然第一个MAG报告于2004年，但应用这些技术的第一个大规模研究直到2015年才发表。从那时起，报道的mag数量呈爆炸式增长，这不仅为99%尚未实验培养的生物体提供了新的见解，而且还极大地扩展了生命之树。除了捕获微生物的生物多样性外，这些mag还有助于以基因组为中心了解它们在群落中的功能作用，以及它们如何相互作用和周围环境。应用研究的实质性部分利用这些发现来恢复受干扰的微生物组到健康状态或利用它们编码的酶。该提案侧重于MGnify，该资源已经在微生物群落研究中发挥了四个主要作用：(i)它有助于捕获当前生成的pb序列数据；（ii）为用户提供对计算资源的访问，以进行宏基因组组装；（iii）通过分析微生物组衍生序列数据产生新知识，并通过网站和API向用户群体展示；（iv）已开始捕获原核生物mag。在本提案中，我们将扩展MGnify以使用创新的新方法恢复真核mag，并捕获MGnify组装中的病毒。这些真核生物和病毒基因组的非冗余目录将用于补充现有的MGnify基因组。为了完善MAG生成过程，我们建议开发额外的管道来识别和去除原核MAG中发现的污染物。除了生成覆盖整个微生物分类群范围的高质量MAGs外，我们还将与基因组分类数据库（GTDB）协调工作，以确保新发现的细菌多样性在其中得到适当的代表，因为它是分类分类中使用最广泛的资源之一。在此基础上，我们将加强宏基因组序列提交系统，以更好地满足所有数据类型，并改进数据交换的内部机制，以便MGnify可以代表用户执行提交，并获得所有数据类型的访问权限，无论数据是公开的还是私人的（预发表），只要适当的用户同意。最后，除了更新我们分析管道中的参考数据库外，我们还将改进目前数据库中代表性较差的碳水化合物代谢酶的注释。总的来说，这些发展将加强MGnify对微生物组研究界的至关重要性。它将作为推动综合微生物组研究及其转化为现实世界应用的基础知识库。

项目成果

MGnify: the microbiome sequence data analysis resource in 2023.

• DOI: 10.1093/nar/gkac1080
• 发表时间: 2023-01-06
• 期刊: NUCLEIC ACIDS RESEARCH
• 影响因子: 14.9
• 作者: Richardson, Lorna;Allen, Ben;Baldi, Germana;Beracochea, Martin;Bileschi, Maxwell L.;Burdett, Tony;Burgin, Josephine;Caballero-Perez, Juan;Cochrane, Guy;Colwell, Lucy J.;Curtis, Tom;Escobar-Zepeda, Alejandra;Gurbich, Tatiana A.;Kale, Varsha;Korobeynikov, Anton;Raj, Shriya;Rogers, Alexander B.;Sakharova, Ekaterina;Sanchez, Santiago;Wilkinson, Darren J.;Finn, Robert D.
• 通讯作者: Finn, Robert D.

The European Nucleotide Archive in 2022.

• DOI: 10.1093/nar/gkac1051
• 发表时间: 2023-01-06
• 期刊: NUCLEIC ACIDS RESEARCH
• 影响因子: 14.9
• 作者: Burgin, Josephine;Ahamed, Alisha;Cummins, Carla;Devraj, Rajkumar;Gueye, Khadim;Gupta, Dipayan;Gupta, Vikas;Haseeb, Muhammad;Ihsan, Maira;Ivanov, Eugene;Jayathilaka, Suran;Kadhirvelu, Vishnukumar Balavenkataraman;Kumar, Manish;Lathi, Ankur;Leinonen, Rasko;Mansurova, Milena;McKinnon, Jasmine;O'Cathail, Colman;Pauperio, Joana;Pesant, Stephane;Rahman, Nadim;Rinck, Gabriele;Selvakumar, Sandeep;Suman, Swati;Vijayaraja, Senthilnathan;Waheed, Zahra;Woollard, Peter;Yuan, David;Zyoud, Ahmad;Burdett, Tony;Cochrane, Guy
• 通讯作者: Cochrane, Guy

Establishing the ELIXIR Microbiome Community

建立 ELIXIR 微生物群落

• DOI: 10.12688/f1000research.144515.1
• 发表时间: 2024
• 期刊: F1000Research
• 作者: Finn R

MGnify Genomes: A Resource for Biome-specific Microbial Genome Catalogues.

• DOI: 10.1016/j.jmb.2023.168016
• 发表时间: 2023-07-15
• 期刊: JOURNAL OF MOLECULAR BIOLOGY
• 影响因子: 5.6
• 作者: Gurbich, Tatiana A.;Almeida, Alexandre;Beracochea, Martin;Burdett, Tony;Burgin, Josephine;Cochrane, Guy;Raj, Shriya;Richardson, Lorna;Rogers, Alexander B.;Sakharova, Ekaterina;Salazar, Gustavo A.;Finn, Robert D.
• 通讯作者: Finn, Robert D.