BBSRC Institute Strategic Programme: Decoding Biodiversity (DECODE) - Partner Grant

21世纪初，人类基因组的发表具有里程碑意义，改变了我们研究生物学的方式，并对医学产生了巨大影响。这预示着基因组学的一个新时代，最初以模式生物和更重要的经济物种的基因组的产生和分析为主导。与此同时，基因组技术使微生物学的进步成为可能，例如解开复杂的群落，或者像在大流行中所看到的那样，识别SARS-CoV-2的新的新变种。这些快速进步是由高通量测序技术和组装和分析基因组的软件的创新推动的。最近，这些领域的阶段性变化使大规模产生高质量基因组成为可能，使地球生物基因组计划等雄心勃勃的项目成为可能，其目标是为所有真核生物创造基因组。此外，这意味着不再局限于一个物种的单一基因组，现在可以产生多个基因组，帮助捕捉物种的多样性。然而，基因组数据的规模和复杂性构成了一个分析挑战，公共和私营部门(我们的利益相关者)迫切需要工具、专业知识和能力来将基因组和长期阅读的技术转化为发现。解码生物多样性(DECODE)研究计划的成果将满足这一需求，BBSRC转型技术主题，以及政府对基因组学和生物信息学投资和创新的优先次序(英国创新战略)。DECODE汇集了计算生物学、数学和基因组学方面的专业知识。它建立在我们之前的核心战略计划“基因组促进粮食安全”、跨研究所战略计划(ISP)“设计未来小麦”和Quadram ISP“肠道微生物与健康”的创新基础上。此外，它还借鉴了通过研究能力建设方案“成长哥伦比亚”获得的经验和网络，并作为达尔文生命之树(DToL)联盟的合作伙伴。DECODE通过三个相互关联的工作包提供：工作包1将开发调查生物多样性的工具和技术。具体地说，这包括制定以下方法：比较物种内和物种间的多个基因组，以确定结构变化；利用多个基因组改进基因组中编码和调节区的注释；解决细菌群落的复杂性和这些群落内的生物学作用；部署序列，作为环境群落的实时传感器。与我们的合作伙伴IBM和Eagle基因组公司合作，我们将使开发的软件和工作流程强大、可部署和可扩展。Work Package 2将使用WP1中开发的工具来调查公开可用的基因组中的生物多样性。我们将使用多种分析方法来：将功能分配给基因组“暗物质”--目前未知功能的基因；研究植物化学多样性的基础机制；并确定关键农业作物和水产养殖物种遗传多样性的驱动机制。工作包3将使用长阅读测序技术和WP1开发的工具来发现和探索生物多样性。具体地说，将研究日益复杂的系统(肠道、厌氧消化器和土壤)中的群落结构如何随着时间的推移而变化。此外，通过量化基因含量的变化，WP3将致力于确定一个社区的生物功能是如何变化的，并将这些与社区健康联系起来。为了实现这一计划，我们建立了四个关键的战略合作伙伴关系：RBG Kew将提供植物新陈代谢、泛基因组学和作物野生近亲方面的专业知识，IBERS将提供英国孤儿作物的专业知识，英国生态与水文学中心将提供土壤样本和访问上下文数据集，以及IBM Research将支持工具的部署和可扩展性。

The start of the 21st Century saw the landmark publication of the human genome, changing the way we do biology and having a huge impact on medicine. This heralded a new era of genomics that was initially dominated by the generation and analysis of genomes of model organisms and more economically important species. Concurrently, genome technologies have enabled advances in microbiology, such as disentangling complex communities or, as has been seen in the pandemic, identifying new emerging variants of SARS-CoV-2. These rapid advances have been driven by innovation in high-throughput sequencing technologies and software to assemble and analyse genomes. Recently, step changes in these areas enable the generation of high-quality genomes at scale, making ambitious projects like the Earth Biogenome Project, with the goal of generating genomes for all eukaryotic life, feasible. Furthermore, it means that rather than being limited to a single genome for a species, it is now possible to generate multiple genomes, helping to capture the diversity of the species. However, the scale and complexity of this genomic data presents an analytical challenge and there is a pressing need across the public and private sectors (our stakeholders) for tools, expertise and capacity to translate genomes and long-read technologies into discoveries. The outputs of the Decoding Biodiversity (DECODE) research programme will deliver to this need, to the BBSRC Transformative Technologies theme, and to the government prioritization of investment and innovation in genomics and bioinformatics (UK Innovation Strategy).DECODE brings together expertise in computational biology, mathematics and genomics. It builds on innovations from our previous core strategic programme "Genomics for Food Security", the cross Institute Strategic Programme (ISP) "Designing Future Wheat", and the Quadram ISP "Gut Microbes and Health". In addition, it draws on the experience and networks gained through the research capacity-building programme "Grow Colombia", and as a partner in the Darwin Tree of Life (DToL) consortium. DECODE is delivered through three interconnected work packages:Work package 1 will develop tools and techniques to investigate biodiversity. Specifically, this includes developing methods for: comparing multiple genomes within and across species to identify structural changes; using multiple genomes to improve annotation of coding and regulatory regions in the genome; resolving complexity of bacteria communities and biological roles within those communities; the deployment of sequences as real-time sensors of environmental communities. With our partners IBM and Eagle genomics, we will make the software and workflows developed are robust, deployable and scalable.Work package 2 will use the tools developed in WP1 to investigate biodiversity in publicly available genomes. We will use multiple analytical approaches to: assign function to genomic "dark matter"-genes of currently unknown function; investigate mechanisms underpinning chemical diversity in plants; and identify mechanisms driving genetic diversity in key agricultural crops and aquaculture species.Work Package 3 will use long read sequencing technologies and the tools developed in WP1 to uncover and explore biodiversity. Specifically, how community structures change over time in increasingly complex systems (the gut, anaerobic digesters and soil) will be investigated. Furthermore, through quantifying gene content changes, WP3 will aim to identify how biological functions change in a community and link these to community health.To deliver this programme, we have established four key strategic partnership: RBG Kew will provide expertise in plant metabolism, pangenomics and crop wild relatives, IBERS brings expertise in UK orphan crops, the UK Center for Ecology & Hydrology will provide soil samples and access to contextual datasets, and IBM Research will support deployment and scalability of tools.