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Enabling Comparative Pangenomics

实现比较泛基因组学

基本信息

批准号：
9887711
负责人：
Paul Flicek
金额：
$ 65.99万
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：实现比较泛基因组学对于该领域的许多人来说，很明显，我们正在迅速迈向脊椎动物比较的黄金时代基因组学，其中数千个不同物种的高质量基因组是公开可用的并用于了解人类基因组。尽管可用基因组的增长带来了机遇，用于比较完整基因组的软件相对停滞，大多数软件开发较旧且能力有限。为了解决这种情况，我们将创建一个强化工具包基因组比较和注释，可以稳健地应用于数千个脊椎动物基因组。到展示这个工具包并将其结果提供给更广泛的基因组学社区，我们将应用它来创建现有 UCSC 和 Ensembl 基因组浏览器中的资源将包含数千个脊椎动物基因组。大型、组织良好的联盟已经联合起来应对测序的挑战并组装脊椎动物基因组。我们的联盟将构成这些项目分析的支柱，我们的综合他们的数据将创造出一种资源，其数量远远大于其他资源的总和。一系列规模较小、分散且无法直接比较的努力。我们将聚集超过600人在提案的第一年，我们就将脊椎动物基因组纳入了我们提议的资源中，并迅速取得了成果。随着可用参考基因组的增长，过去十年的特点是群体测序项目的爆炸式增长。尽管大部分已编录的人类变异都有很大的差异最近的进化起源，有巨大的机会结合起来，以便更好地理解内部和外部使用群体遗传学模型来研究物种间的变化。我们将创建泛基因组软件来（i）避免物种比较中的参考偏差（即避免假设哪些等位基因是固定的物种之间的比较，这对于慈鲷等准物种很重要），（ii）允许祖先等位基因进行全面估计，包括那些结构变化的一部分，并且（iii）更容易实现平衡选择的研究。为了演示综合变异积分的实用性，我们将为猿类创建泛基因组原型。我们将使用该图来识别祖先等位基因并动态转换物种和装配版本之间的注释，并通过种群映射实验中，我们将展示它在打字分离但古老的变异方面的力量。利用知识猿进化，我们最终将扩展该图以充分模拟人类最复杂的区域基因组。