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: 10020425
• 负责人: Paul Flicek
• 金额: $ 251.54万
• 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/10020425
• 关键词: Adoption; Affect; Bioinformatics; Biomedical Research; Cataloging; Catalogs; Clinical; Collaborations; Collection; Communication; Communities; Community Outreach; Complement; Computer software; Data; 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; data tools; epigenome; epigenomics; experience; experimental study; genetic analysis; genetic element; genetic information; genetic variant; genome analysis; genome browser; genome resource; genomic platform; human genomics; human pangenome; 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; variant detection; 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 已经构建了遗传学和基因组学。它是几乎所有人类基因组学的分析基板 应用程序包括读取对齐，变体检测，变体解释，功能注释， 种群遗传学和表观基因组分析。从更基本的意义上讲，参考基因组也是 用于系统报告和比较研究结果的坐标系，以及分类 人类中存在的重要遗传元素和变体。随着基因组方法继续前进 临床领域，参考基因组对于遗传筛查和 精密医学。然而，人们越来越多地认为当前的参考基因组已过时。 主要限制是参考并不能充分代表人类的基因组多样性 人口，这导致了“参考偏见”，从而对遗传分析的准确性产生不利影响。到 解决这个问题，有必要构建一个参考泛人基因组（即一个“泛基因组”） 我们集体中存在的常见变体，单倍型和功能元素的完整补充 基因组。为了实现这一目标，我们建议形成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件开始，我们将创建一个高的 序列比对和变体的质量图，并使用我们具有的基因组图方法 开创性的是建立自然代表遗传多样性的泛基因组资源。我们将注释 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。 与社区合作，我们将培养一个合作的基因组分析工具的新生态系统 新参考。我们将通过征求用户反馈和 建立可扩展的生物信息学方法和针对性的测序方案，以解决错误和 改善特定的基因组区域。我们进一步建议组成一个有效的物流协调中心 在整个财团的层面上组织沟通和协作活动，以确保所有人 程序组件正在携手合作。最后，从角度来看，最重要的是 用户采用，我们设计了一个集成的泛基因组过渡计划，涉及广泛的社区 通过宣传和教育在工具开发人员和最终用户的水平上进行参与。总的来说，这些 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来支持 下一代人类遗传学和临床实践。