Enabling Comparative Pangenomics

实现比较泛基因组学

基本信息

批准号：
10117276
负责人：
Paul Flicek
金额：
$ 64.77万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-02 至 2023-12-31
项目状态：
已结题

项目摘要

Project Summary: Enabling Comparative Pangenomics To many in the field, it is clear that we are moving rapidly toward a golden age of vertebrate comparative genomics in which thousands of high quality genomes of different species are publicly available and used in understanding the human genome. Despite the opportunity presented by the growth in available genomes, there has been relative stagnation in the software used to compare complete genomes, most of the software developed being old and limited in capabilities. To remedy this situation, we will create a hardened toolkit for genome comparison and annotation that can be robustly applied to thousands of vertebrate genomes. To demonstrate this toolkit and deliver its results to the broader genomics community, we will apply it to create a resource within the existing UCSC and Ensembl Genome Browsers that will incorporate thousands of vertebrate genomes. Large, well organized consortia have coalesced to take on the challenge of sequencing and assembling vertebrate genomes. Our alignments will form a backbone of these projects’ analysis, and our synthesis of their data will create a resource that is much greater than the sum of what might otherwise be a series of smaller, fragmented and not directly comparable efforts. We will gather together more than 600 vertebrate genomes into our proposed resource in the first year of the proposal, rapidly delivering results. Paralleling the growth in available reference genomes, the last decade has been marked by an explosion in population sequencing projects. Although much of the cataloged human variation has a very recent evolutionary origin, there is a tremendous opportunity to combine and so better understand intra- and inter- species change using models from population genetics. We will create pangenome software to (i) avoid reference bias in species comparisons (i.e. avoiding assumptions about which alleles are fixed when comparing between species, which is important in quasi-species such as cichlids), (ii) allow ancestral alleles to be comprehensively estimated, including those that are part of structural variation, and (iii) more easily enable the study of balancing selection. To demonstrate the utility of comprehensive variation integration we will create a prototype of a pan-genome for the apes. We will use this graph to identify ancestral alleles and to dynamically convert annotations between species and assembly versions, and, via population mapping experiments, we will demonstrate its power for typing segregating but ancient variation. Using knowledge of ape evolution, we will ultimately extend this graph to adequately model the most complex regions of the human genome.

项目摘要：启用比较pangenomics 对于该领域的许多基因组学，其中数千种不同物种的高质量基因组公开可用，并用于了解人类基因组。尽管可用基因组的增长带来了机会，但用于比较完整基因组的软件中存在相对停滞，大多数软件发展的能力是旧的和有限的。为了纠正这种情况，我们将为基因组比较和注释可以鲁棒化地应用于数千个脊椎动物基因组。到展示此工具包并将其结果传递给更广泛的基因组学社区，我们将使用它来创建一个现有的UCSC和Ensembl基因组浏览器中的资源，这些浏览器将包含数千个脊椎动物基因组。大型，井井有条的财团已经结合了测序的挑战并组装脊椎动物基因组。我们的一致性将形成这些项目分析的骨干，我们他们的数据的综合将创建一个资源，该资源比原本可能是的总和要大得多一系列较小的，分散的且不直接比较的努力。我们将聚集600多个在提案的第一年，脊椎动物基因组进入了我们提出的资源，迅速提供结果。在可用参考基因组中的生长并行，过去十年已被标记人口测序项目中的爆炸。尽管许多人的人类变异都非常最近的进化起源，有一个巨大的机会可以结合起来，因此更好地了解内部和内部和种间使用种群遗传学的模型变化。我们将创建pangenome软件以（i）避免物种比较中的参考偏差（即避免在等位基因时固定哪些等位基因时的假设比较物种，这在诸如丽鱼科等准物种中很重要），（ii）允许祖先等位基因全面估计，包括属于结构变化的部分，以及（iii）更容易启用平衡选择的研究。为了证明综合变化整合的实用性，我们将为猿创建泛基因组的原型。我们将使用此图来识别祖先等位基因和通过种群映射动态转换物种和装配版本之间的注释实验，我们将展示其输入分离但古老的变化的力量。使用知识猿的演变，我们最终将扩展该图，以充分地模拟人类最复杂的区域基因组。