The WashU-UCSC-EBI Human Genome Reference Center

项目概要（总体：人类基因组参考中心） 人类参考基因组是构建现代人类基因组框架的基础资源 遗传学和基因组学已经建立。它是几乎所有人类基因组学的分析基质 应用包括读段比对、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，参考基因组还充当 一个坐标系统，用于系统地报告和比较不同研究的结果， 重要的遗传元素和变异存在于人类。随着基因组学方法继续向 在临床领域，参考基因组对于遗传筛查将变得越来越重要， 精准医疗然而，越来越多的人意识到，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。 这导致了“参考偏差”，对遗传分析的准确性产生了不利影响。到 解决这个问题，有必要建立一个参考泛人类基因组--即，一个“泛基因组”， 在我们的集体中存在的常见变异，单倍型和功能元件的完整补充 基因组为了实现这一目标，我们建议成立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， 率先建立了一个泛基因组资源，自然代表遗传多样性。我们将注释 泛基因组的基因和其他元素，并分享这一资源广泛和公开供公众使用。 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， 新的参考。我们将通过征求用户反馈意见， 建立可扩展的生物信息学方法和用于解决错误的靶向测序方案， 改善特定的基因组区域。我们还建议成立一个后勤协调中心， 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， 用户采用，我们已经制定了一个综合的泛基因组过渡计划，涉及广泛的社区 通过在工具开发者和最终用户层面的推广和教育进行参与。综上所述各项 努力将创建一个新的人类基因组参考，软件生态系统和专家用户群，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.