Beyond a single reference: Building high quality graph genomes capturing global diversity

超越单一参考：构建捕获全球多样性的高质量图基因组

• 批准号: BB/T019468/1
• 负责人: James Prendergast
• 金额: $ 55.62万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT019468%2F1
• 关键词: Beyond; single; reference; Building; quality

Most species show substantial amounts of genetic diversity between individuals and populations. However, large amounts of this genetic diversity are missing, and therefore inaccessible, using current reference genomes. Almost all references are derived from just one or a small handful of individuals, which are collapsed into a single pseudo-haploid representation, meaning hundreds of megabases of pan-genome DNA sequence are missing from most mammalian reference sequences. This includes regions likely to be associated with important phenotypes such as environmental adaptation and disease tolerance. Not only can these regions not be studied in current analyses reliant upon these genomes, but several studies have highlighted how reliance on these haploid references deleteriously bias analyses, even in the regions of the genome that are present. Reference mapping biases impact analyses as fundamental as genetic variant calling and gene expression studies, which ultimately means they are likely to be deleteriously affecting thousands of studies a year.The emerging field of genome graphs aims to mitigate these issues by incorporating the diversity observed across individuals into a single graph representation of the species' pan-genome. This ensures all genomic regions can be captured and mitigates issues such as mapping biases by incorporating all known alleles and haplotypes as alternative routes through the graph. Despite their advantages, few high-quality graph genomes are currently available, primarily because the generation, annotation and visualisation of graph genomes is challenging, providing barriers to their wider use. The aim of this project is to drive forward the use of graph genomes by addressing these issues. By producing reusable, containerised pipelines for generating and working with genome graphs, researchers will be able to rapidly generate and update graph genomes for their species of interest. We will use these pipelines and data from previous BBR projects to generate and make available the first high quality cattle graph genome resource, encompassing the spectrum of genetic variants from large structural variants across sub-species to single nucleotide variants within breeds. To ensure graph genomes can be widely accessed the third and final resource will be a new portal for viewing richly annotated genome graphs. By facilitating the rapid creation of graph genomes compatible with relevant downstream alignment and variant calling software freely and publicly accessible, enabling their downstream visualisation, and developing a new cattle graph genome, we expect this project to make a significant contribution to livestock research, ranging from studies mapping genetic loci linked to economically important traits to those understanding the evolution of species. Additionally, the pipelines developed will be immediately transferrable to the production of graph genomes for other species, significantly extending the impact of project outputs.

大多数物种在个人和人群之间显示出大量的遗传多样性。但是，使用当前的参考基因组缺少大量这种遗传多样性，因此无法访问。几乎所有的参考都来自一个或少数个个体，这些个体被折叠成单个伪 - 二倍体表示，这意味着大多数哺乳动物参考序列中缺少了数百个泛基因组DNA序列的数百个兆座。这包括可能与重要表型有关的区域，例如环境适应和疾病耐受性。这些区域不仅不能在依赖这些基因组的当前分析中进行研究，而且几项研究强调了如何依赖这些单倍体参考文献有害分析，即使在存在的基因组区域也是如此。参考映射偏见影响与遗传变异呼叫和基因表达研究的基本分析，这最终意味着它们每年可能会有害影响数千个研究。基因组图的新兴领域旨在通过将跨个体跨个体的多样性纳入该物种的单个图形表示泛群。这样可以确保可以捕获所有基因组区域，并通过将所有已知的等位基因和单倍型纳入图形途径来减轻诸如映射偏差之类的问题。尽管它们具有优势，但目前很少有高质量的图基因组，主要是因为图基因组的产生，注释和可视化是具有挑战性的，这为其更广泛的使用提供了障碍。该项目的目的是通过解决这些问题来推动图形基因组的使用。通过生成可重复使用的容器化管道来生成和使用基因组图，研究人员将能够快速生成和更新图形基因组，以引起其感兴趣的物种。我们将使用以前BBR项目的这些管道和数据来生成并提供第一个高质量的牛图基因组资源，包括从跨亚种的大型结构变体到品种中的单核苷酸变体的遗传变体的光谱。为了确保可以广泛访问图形基因组，第三和最终资源将成为查看丰富注释的基因组图的新门户。通过促进图形基因组的快速创建与相关的下游对齐和可自由公开访问的变体呼叫软件兼容，使其下游可视化以及开发新的牛图基因组，我们希望该项目能够为牲畜研究做出重要的贡献，包括研究基因在经济上重要的研究，从而使这些物种链接到经济上重要的物种都可以养育那些人的养育，并能够实现这些效果。此外，开发的管道将立即转移到其他物种的图基因组生产中，从而大大扩展了项目产出的影响。

项目成果

Profiling the immune epigenome across global cattle breeds.

• DOI: 10.1186/s13059-023-02964-3
• 发表时间: 2023-05-22
• 期刊: GENOME BIOLOGY
• 影响因子: 12.3
• 作者: Powell, Jessica;Talenti, Andrea;Fisch, Andressa;Hemmink, Johanneke D.;Paxton, Edith;Toye, Philip;Santos, Isabel;Ferreira, Beatriz R.;Connelley, Tim K.;Morrison, Liam J.;Prendergast, James G. D.
• 通讯作者: Prendergast, James G. D.

A cattle graph genome incorporating global breed diversity

纳入全球品种多样性的牛图基因组

• DOI: 10.1101/2021.06.23.449389
• 发表时间: 2021
• 作者: Talenti A

nf-LO: A scalable, containerised workflow for genome-to-genome lift over

nf-LO：用于基因组到基因组转移的可扩展、容器化工作流程

• DOI: 10.1101/2021.05.25.445595
• 发表时间: 2021
• 作者: Talenti A

A cattle graph genome incorporating global breed diversity.

• DOI: 10.1038/s41467-022-28605-0
• 发表时间: 2022-02-17
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Talenti A;Powell J;Hemmink JD;Cook EAJ;Wragg D;Jayaraman S;Paxton E;Ezeasor C;Obishakin ET;Agusi ER;Tijjani A;Amanyire W;Muhanguzi D;Marshall K;Fisch A;Ferreira BR;Qasim A;Chaudhry U;Wiener P;Toye P;Morrison LJ;Connelley T;Prendergast JGD
• 通讯作者: Prendergast JGD

High performance imputation of structural and single nucleotide variants in Atlantic salmon using low-coverage whole genome sequencing

使用低覆盖率全基因组测序对大西洋鲑鱼的结构和单核苷酸变异进行高性能估算

• DOI: 10.1101/2023.03.05.531147
• 发表时间: 2023
• 作者: Gundappa M