HIGH QUALITY HUMAN AND NON-HUMAN PRIMATE GENOME ASSEMBLIES

 描述（由申请人提供）：一组多样且高度准确的灵长类动物基因组对于进一步了解人类变异和遗传疾病的进化背景至关重要。该提案的主要目标是生成更好地代表人类多样性复杂性的高质量参考基因组（即，大陆人类参考基因组），并显着提高索引非人灵长类动物（NHP）基因组的质量，达到更符合当前人类基因组的质量水平（GRCh 38）。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级别的分辨率。最终结果将是一组NHP基因组，其代表每个基因组的组装连续性和代表性的>10-20倍改进，其中>95%的常染色质独特区域被完全测序、注释和定相。该项目包括一个特别强调的差距和基因丰富的复杂序列结构，这一直是灵长类动物基因组中最棘手的常染色质区域。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。该项目的目标是完整的常染色质序列，其中>95%的碱基是有序和定向的，>95%的基因模型是完整和注释的。基于改进的基因组支架或使用合成长读段的短读段数据的简单定相的组装增加了价值，但不能满足对研究基因模型、基因调控和遗传变异感兴趣的大多数研究人员的需求。该群体要求解决序列缺口，并且每个基因组以高邻接度组装。我们的战略是提供质量而不是数量，因此，我们专注于以最高质量提供的较小基因组子集，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.