HIGH QUALITY HUMAN AND NON-HUMAN PRIMATE GENOME ASSEMBLIES

 描述(由申请人提供)：收集不同的和高度准确的灵长类基因组对于加深我们对人类变异和遗传病的进化背景的理解至关重要。这一建议的主要目标是产生高质量的参考基因组，以更好地代表人类多样性的复杂性(即大陆人类参考基因组)，并显著提高索引非人类灵长类(NHP)基因组的质量，达到更符合当前人类基因组的质量水平(GRCh38)。我们选择了8个人类基因组和8个NHP进行从头测序和组装，使用单分子实时测序，然后使用实验方法进行广泛的更高水平的分辨率。最终的结果将是一组NHP基因组，它们在组装连续性和每个人类基因组的表示方面都提高了10-20倍，其中&gt；95%的常染色体独特区域被完全测序、注释和分阶段。该项目包括对缺口和富含基因的复杂序列结构的特别强调，这是灵长类基因组中最难处理的常染色质区域。虽然有许多衡量基因组组装完成和测序的指标，但我们的指标是实用的。这个项目的目标是完整的等色序列，其中95%的碱基是有序的和定向的，95%的基因模型是完整的和注释的。基于改进的基因组支架的组装或使用合成长读数对短读数据进行简单的阶段化增加了价值，但不能满足大多数对研究基因模型、基因调控和遗传变异感兴趣的研究人员的需求。该社区要求解决序列差距，并以高邻接性组装每个基因组。我们的战略是提供质量高于数量，因此，我们专注于以最高质量交付的一小部分基因组，建立在测序技术和组装的最新进展基础上。

 DESCRIPTION (provided by applicant): A collection of diverse and highly accurate primate genomes are critical to further our understanding of human variation and the evolutionary context of genetic disease. The main goal of this proposal is to generate high quality reference genomes that better represent the complexity of human diversity (i.e., continental human reference genomes) and that significantly improve the quality of index non-human primate (NHP) genomes, reaching a quality level more in line with the current human genome (GRCh38). We have selected 8 human genomes and 8 NHP for de novo sequencing and assembly using single molecule real-time sequencing followed by extensive higher-level resolution using experimental approaches. The end-result will be a set of NHP genomes that represent a >10-20 fold improvement in assembly continuity and representation of each and human genomes where >95% of euchromatic unique regions are fully sequenced, annotated, and phased. This project includes a special emphasis on gaps and gene-rich complex sequence structure, which have been the most intractable euchromatic regions of primate genomes. While there are many metrics of genome assembly completion and sequencing, ours is a practical one. The goal of this project is complete euchromatic sequence where >95% of the bases are ordered and oriented, and >95% of gene models are complete and annotated. Assemblies based on improved genome scaffolding or simple phasing of short read data using synthetic long reads add value but do not meet the needs of most researchers who are interested in studying gene models, gene regulation, and genetic variation. The community requires that sequence gaps are resolved and each genome is assembled at high contiguity. Our strategy is to deliver quality over quantity, and as such we are focused on a smaller subset of genomes delivered at the highest quality, building upon very recent advances in sequencing technology and assembly.