The WashU-UCSC-EBI Human Genome Reference Center

华盛顿大学-UCSC-EBI 人类基因组参考中心

• 批准号: 9906005
• 负责人: Paul Flicek
• 金额: $ 256.51万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-18 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906005
• 关键词: Adoption; Affect; Bioinformatics; Biomedical Research; Cataloging; Catalogs; Clinical; Collaborations; Collection; Communication; Communities; Community Outreach; Complement; Computer software; Data; Detection; Ecosystem; Education and Outreach; Educational Materials; Elements; Ensure; Feedback; Fostering; Foundations; Genes; Genetic Screening; Genetic Variation; Genome; Genomic Segment; Genomics; Genotype; Goals; Graph; Haplotypes; Human; Human Genetics; Human Genome; Individual; Leadership; Logistics; Maps; Metadata; Methods; Modeling; Modernization; National Human Genome Research Institute; Phase; Population; Population Genetics; Production; Program Sustainability; Protocols documentation; Reporting; Reproducibility; Research; Resource Sharing; Resources; Role; Sequence Alignment; Standardization; Structure; System; Time; Training; Update; Variant; Work; base; clinical practice; cohort; data management; data resource; epigenome; epigenomics; experience; experimental study; genetic analysis; genetic element; genetic information; genetic variant; genome analysis; genome browser; genomic platform; human genomics; human reference genome; improved; innovation; meetings; member; next generation; operation; outreach; outreach program; pan-genome; precision medicine; preservation; programs; reference genome; symposium; targeted sequencing; tool; trait; user-friendly; virtual; web portal

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.

项目摘要（总体：人类基因组参考中心） 人类参考基因组是现代人类框架的基础资源 它是几乎所有人类基因组学的分析基础。 应用包括读段比对、变异检测、变异解释、功能注释、 从更基本的意义上来说，参考基因组也可以用作群体遗传学和表观基因组分析。 用于系统地报告和比较研究结果以及对研究结果进行编目的坐标系 随着基因组方法不断进军人类中存在的重要遗传元件和变异。 在临床领域，参考基因组对于基因筛查和诊断将变得越来越重要。 然而，人们越来越意识到当前的参考基因组已经过时。 主要限制是参考文献不能充分代表人类基因组多样性 人口，这会导致“参考偏差”，对遗传分析的准确性产生不利影响。 为了解决这个问题，有必要建立一个参考泛人类基因组——即“泛基因组”——代表 我们集体中存在的常见变异、单倍型和功能元素的完整补充 为了实现这一目标，我们建议建立 WashU-UCSC-EBI 人类基因组参考。 从数据生产中心生成的基因组组装开始，我们将创建一个高水平的基因组组装中心。 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 率先建立了自然代表遗传多样性的泛基因组资源。 基因和其他元素的泛基因组，并广泛、公开地共享该资源以供公众使用。 我们将与社区合作，培育一个新的基因组分析工具生态系统。 我们将通过征求用户反馈和意见来维护并逐步改进该参考。 建立可扩展的生物信息学方法和有针对性的测序方案以解决错误和 我们进一步建议建立一个高效的后勤协调中心。 在整个联盟层面组织沟通和协作活动，确保所有 最后，也许最重要的是，在展台上，各个程序组件是齐头并进的。 为了提高用户采用率，我们制定了一个涉及广泛社区的综合泛基因组过渡计划 总而言之，通过工具开发人员和最终用户层面的宣传和教育来参与。 将创建新的人类基因组参考工作、软件生态系统和专家用户群来支持 下一代人类遗传学和临床实践。