Enabling Comparative Pangenomics

项目概要：实现比较泛基因组学 对许多该领域的人来说，很明显，我们正在迅速走向脊椎动物比较研究的黄金时代。 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会， 用于比较完整基因组的软件相对停滞， 开发的是旧的和有限的能力。为了纠正这种情况，我们将创建一个强化的工具包， 基因组比较和注释，可以稳健地应用于成千上万的脊椎动物基因组。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一个 现有UCSC和Ensembl基因组浏览器中的资源，将整合数千个 脊椎动物基因组大型的、组织良好的财团已经联合起来接受测序的挑战 组装脊椎动物的基因组我们的路线将成为这些项目分析的支柱， 综合他们的数据将创造一个资源，这是远远大于什么，否则可能是一个 一系列规模较小、零散且无法直接比较的努力。我们将聚集600多名 我们在提案的第一年就将脊椎动物基因组纳入我们的提案资源，并迅速取得成果。 随着可用参考基因组的增长，过去十年的特点是 人口测序项目的爆炸。尽管人类的许多基因变异 最近的进化起源，有一个巨大的机会，联合收割机，因此更好地了解内部和 利用种群遗传学模型研究物种间的变化。我们将创建泛基因组软件，以（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，这是重要的准物种，如慈鲷），（ii）允许祖先等位基因， （iii）更容易实现， 平衡选择的研究。为了证明综合变分积分的实用性，我们将 为猿类创造了一个泛基因组的原型。我们将用这个图来识别祖先的等位基因， 动态转换物种和汇编版本之间的注释，并通过人口映射 实验中，我们将证明它的分型分离，但古老的变化的力量。利用知识 猿进化，我们最终将扩展这一图表，充分模拟人类最复杂的地区 基因组

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.