Enabling Comparative Pangenomics

项目摘要：启用比较泛基因组学 对于该领域的许多人来说，很明显，我们正在迅速走向脊椎动物相对 一种基因组学，其中数千个不同物种的高质量基因组可公开获得并用于 了解人类基因组。尽管可用基因组的增长带来了机会， 用于比较全基因组的软件相对停滞不前，大多数软件 发展得既陈旧又能力有限。为了纠正这种情况，我们将为以下内容创建一个强化工具包 基因组比较和注释，可以很好地应用于数千个脊椎动物基因组。至 演示此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 现有的UCSC和EnSembl Genome浏览器中的资源，将整合数千个 脊椎动物基因组。组织良好的大型财团已经联合起来，接受排序的挑战 以及组装脊椎动物的基因组。我们的路线将构成这些项目分析的中坚力量，我们的 他们的数据合成将创建一个远远大于否则可能是 一系列规模较小、支离破碎、不可直接比较的努力。我们将汇聚600多个 在提议的第一年，将脊椎动物基因组纳入我们提议的资源，迅速产生结果。 与可用参考基因组的增长相平行，过去十年的标志是 人口测序项目的爆炸性增长。尽管许多编目的人类变异具有非常大的 最近的进化起源，有一个巨大的机会来结合并因此更好地理解内部和 物种间的变化使用了种群遗传学的模型。我们将创建Pangenome软件以(I)避免 物种比较中的参考偏差(即避免假设哪些等位基因是固定的 物种之间的比较，这在准物种中是重要的)，(Ii)允许祖先等位基因 全面估计，包括结构变化的一部分，以及(3)更容易使 平衡选拔的研究。为了演示全面变化集成的效用，我们将 为类人猿创造一个泛基因组的原型。我们将使用这张图来识别祖先的等位基因，并 在物种和程序集版本之间动态转换批注，并通过种群映射 实验中，我们将演示它用于打字分离但古老的变异的能力。利用以下知识 类人猿进化，我们最终将扩展这张图，以充分模拟人类最复杂的区域 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.