The WashU-UCSC-EBI Human Genome Reference Center

项目总结(总体：人类基因组参考中心) 人类参考基因组是构建现代人基因组框架的基础资源 遗传学和基因组学已经建立起来了。它是几乎所有人类基因组学的分析底物 应用包括读对齐、变体检测、变体解释、功能注释、 群体遗传学和表观基因组分析。在更基本的意义上，参考基因组也起到了 一个坐标系，用于系统地报告和比较不同研究的结果，并对 存在于人类体内的重要遗传元素和变异。随着基因组学方法继续进军 在临床领域，参考基因组对于基因筛查和 精准医学。然而，人们越来越感觉到，目前的参考基因组已经过时了。 主要的限制是，参考文献不能充分代表人类的基因组多样性。 这会导致“参考偏差”，从而对遗传分析的准确性产生不利影响。至 要解决这个问题，就有必要建立一个参考的泛人类基因组--即，一个代表 我们集体中存在的常见变体、单倍型和功能元件的完整补充 基因组。为了实现这一目标，我们建议建立WASHU-UCSC-EBI人类基因组参考 中心。从数据生产中心生成的基因组组装开始，我们将创建一个高 序列比对和变异的质量图，并使用我们拥有的基因组图方法 率先建立了一个自然代表遗传多样性的泛基因组资源。我们将对 基因和其他元素的泛基因组，并广泛和公开地共享这一资源供公众使用。 与社区合作，我们将培育一个新的基因组分析工具生态系统，与此一起工作 新的参考文献。我们将通过征求用户反馈意见，保持并逐步完善参考文献 建立可扩展的生物信息学方法和定向测序方案以解决错误和 改善特定的基因组区域。我们还建议成立一个高效的物流协调中心 在整个联合体层面组织沟通和协作活动，确保所有 程序组件正在携手工作。最后，也许最重要的是从 在用户采用方面，我们设计了一个整合的泛基因组过渡计划，涉及广泛的社区 通过工具开发人员和最终用户层面的外展和教育进行参与。这些加在一起， 将努力创建新的人类基因组参考、软件生态系统和专家用户基础，以支持 下一代人类遗传学和临床实践。

PROJECT SUMMARY (Overall: Human Genome Reference Center) The human reference genome is the foundational resource upon which the framework of modern human genetics and genomics has been constructed. It is the analytical substrate for nearly all human genomics applications including read alignment, variant detection, variant interpretation, functional annotation, population genetics, and epigenomic analysis. In a more basic sense, the reference genome also serves as a coordinate system for systematically reporting and comparing results across studies, and for cataloging the important genetic elements and variants that exist in humans. As genomic methods continue to march into the clinical realm, the reference genome will become increasingly important for genetic screening and precision medicine. Yet, there is a growing sense that the current reference genome has become obsolete. The primary limitation is that the reference does not adequately represent genomic diversity in the human population, and this leads to "reference biases" that adversely affect the accuracy of genetic analyses. To solve this, it is necessary to build a reference pan-human genome – i.e., a "pan-genome" – that represents the full complement of common variants, haplotypes and functional elements that exist in our collective genomes. To accomplish this goal, we propose to form the WashU-UCSC-EBI Human Genome Reference Center. Starting with the genome assemblies generated by the data production center, we will create a high quality map of sequence alignments and variants, and use the genome graph methods that we have pioneered to build a pan-genome resource that naturally represents genetic diversity. We will annotate the pan-genome for genes and other elements, and share this resource broadly and openly for public use. Working with the community, we will foster a new ecosystem of genome analysis tools that work with this new reference. We will maintain and gradually improve the reference by soliciting user feedback and establishing scalable bioinformatic methods and targeted sequenced protocols for resolving errors and improving specific genomic regions. We further propose to form a logistical coordination center that efficiently organizes communication and collaborative activities at the level of the entire consortium, ensuring that all program components are working hand-in-hand. Finally, and perhaps most importantly from the standpoint of user adoption, we have devised an integrated pan-genome transition plan that involves broad community engagement via outreach and education at the level of tool developers and end users. Taken together, these efforts will create a new human genome reference, software ecosystem, and expert user base to support the next generation of human genetics and clinical practice.