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

基本信息

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

项目摘要

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.

大多数物种在个体和种群之间表现出大量的遗传多样性。然而，大量的遗传多样性缺失，因此使用当前的参考基因组无法获取。几乎所有参考文献都仅来自一个或一小部分个体，这些个体被分解为单个伪单倍体表示，这意味着大多数哺乳动物参考序列中缺少数百兆碱基的泛基因组 DNA 序列。这包括可能与环境适应和疾病耐受性等重要表型相关的区域。在目前依赖这些基因组的分析中不仅不能研究这些区域，而且一些研究强调了对这些单倍体参考的依赖如何有害地使分析产生偏差，即使是在存在的基因组区域中也是如此。参考图谱偏差影响分析与遗传变异调用和基因表达研究一样重要，这最终意味着它们可能每年对数千项研究产生有害影响。基因组图谱的新兴领域旨在通过整合个体之间观察到的多样性来缓解这些问题转化为物种泛基因组的单一图形表示。这确保了所有基因组区域都可以被捕获，并通过将所有已知的等位基因和单倍型合并为图表中的替代路线来减轻诸如绘图偏差之类的问题。尽管有其优点，但目前可用的高质量图基因组很少，主要是因为图基因组的生成、注释和可视化具有挑战性，这为其更广泛的使用设置了障碍。该项目的目的是通过解决这些问题来推动图基因组的使用。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其感兴趣物种的图基因组。我们将利用这些管道和之前 BBR 项目的数据来生成并提供第一个高质量的牛图基因组资源，涵盖从跨亚种的大型结构变异到品种内的单核苷酸变异的遗传变异范围。为了确保图基因组可以被广泛访问，第三个也是最后一个资源将是一个用于查看带有丰富注释的基因组图的新门户。通过促进快速创建与相关下游比对和变异调用软件兼容的图基因组，可自由公开访问，实现下游可视化，并开发新的牛图基因组，我们预计该项目将为牲畜研究做出重大贡献，包括研究绘制与经济重要特征相关的遗传位点，以帮助了解物种进化。此外，开发的管道将立即转移到其他物种的图基因组的生产中，从而显着扩大项目产出的影响。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
期刊：
影响因子：
0
作者：
Talenti A
通讯作者：
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
期刊：
影响因子：
0
作者：
Talenti A
通讯作者：
Talenti A

The Bovine Pangenome Consortium: democratizing production and accessibility of genome assemblies for global cattle breeds and other bovine species.

DOI：
10.1186/s13059-023-02975-0
发表时间：
2023-06-19
期刊：
Genome biology
影响因子：
12.3
作者：
通讯作者：

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.

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