Maintaining, improving, and providing the human reference

维护、改进和提供人类参考

• 批准号: 10689155
• 负责人: Ting Wang
• 金额: $ 167.03万
• 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/10689155
• 关键词: ATAC-seq; Benchmarking; Biological Assay; Biology; Breeding; ChIP-seq; Collaborations; Collection; Communities; Complex; Consensus; Data; Data Analyses; Data Set; Databases; Disease; Ecosystem; Ensure; Fostering; Genes; Genetic Variation; Genome; Genome Mappings; Genomic Segment; Genomics; Goals; Graph; Haplotypes; Human; Human Genetics; Individual; International; Intuition; Maps; Metadata; Methods; Modeling; Population; Process; Production; Quality Control; Regulatory Element; Reporting; Research Personnel; Resources; Sampling; Short Tandem Repeat; Single Nucleotide Polymorphism; Structure; System; Testing; Update; Validation; Variant; Work; bioinformatics tool; cohort; data resource; epigenomics; exome sequencing; genetic variant; genome resource; genome sequencing; genomic data; human pangenome; human reference genome; improved; informatics tool; insertion/deletion mutation; migration; pan-genome; preservation; prototype; reference genome; targeted sequencing; telomere; tool; transcriptome sequencing; usability; variant detection; vertebrate genome

PROJECT SUMMARY (Project 1: Maintaining, improving, and providing the human reference) We propose to combine the best current methods and practices with a practical, scalable model to create and share a broadly useful pan-human genome reference (the "pan-genome") based on the assemblies and raw data delivered by the genome production center. The pan-genome reference we propose does not wholly replace the existing GRCh38 reference, rather it substantially builds upon it to create a reference resource that incorporates a much richer representation of human genetic diversity. To deliver this plan, we have assembled a strong group of individuals with complementary expertise that together will construct, share, maintain and improve a state-of-the-art human pan-genome resource. To convert the initial genome assemblies into a high-quality human genome reference cohort we will perform assembly quality control, error correction and validation, mirroring the successful processes we have created for maintaining and improving the existing human reference genome. To make this collection of assemblies comparable, we will then create a comprehensive map of the genomic variants that exist among them. Using the human genome reference cohort and variation map, we will create a human pan-genome reference that has three complementary and essential parts: (i) a sequence graph that encodes the genomes in a non-redundant manner by merging together shared sequences; (ii) a searchable encoding of the haplotypes in the sequence graph, something that the graph itself does not capture; and (iii) a coordinate system that makes it possible to refer to all the variation equally while preserving backwards compatibility with GRCh38. To build this graph we will use tools that we have developed and work across the community to test and prototype the approach, releasing stable and versioned pan-genome references. We also propose a plan to handle error reports from the consortium and broader community, and to fix errors in the references via data analysis, curation and targeted sequencing. We will follow a completely open model to ensure all data – primary data, genome assemblies and pan-genome reference – are simultaneously available via AnVIL and accessioned through appropriate international databases. We will add value to this resource by creating a core set of pan-genome functional annotations, focusing primarily on genes. To make working with and migrating to the proposed pan-genome reference straightforward, we will foster the creation of new and updated tools. Our strategy harnesses the community by working with tool developers, in particular establishing and promoting exchange formats and creating benchmarks to promote best-of-breed community methods.

项目概要（项目1：维护、改进和提供人类参考） 我们建议联合收割机将当前最好的方法和实践与一个实用的、可扩展的模型相结合， 并基于组装和共享广泛有用的泛人类基因组参考（“泛基因组”） 基因组生产中心提供的原始数据。我们提出的泛基因组参考并不完全 取代现有的GRCh 38参考，而不是它基本上建立在它创建一个参考资源 它包含了更丰富的人类遗传多样性的表现。为了实现这一计划，我们 组建了一个强大的团队，他们拥有互补的专业知识，将共同建设，分享， 维护和改进最先进的人类泛基因组资源。将最初的基因组 组装成一个高质量的人类基因组参考队列，我们将进行组装质量控制， 错误纠正和验证，反映了我们为维护和 改进现有的人类参考基因组。为了使这个程序集集合具有可比性，我们将 然后创建一个存在于它们之间的基因组变异的综合图谱。利用人类基因组 参考队列和变异图，我们将创建一个人类泛基因组参考， 互补和必要部分：（i）以非冗余方式编码基因组的序列图 通过将共享序列合并在一起的方式;（ii）序列中单体型的可搜索编码 图形，图形本身无法捕捉的东西;（iii）一个坐标系，使其成为可能 在保留与GRCh 38的向后兼容性的同时，平等地引用所有变体。为了建立这个图表 我们将使用我们开发的工具，并在整个社区中工作，以测试和原型的方法， 发布稳定和版本化的泛基因组参考。我们还提出了一个计划，以处理来自 联盟和更广泛的社区，并通过数据分析，策展和 定向测序。我们将遵循完全开放的模式，以确保所有数据-原始数据，基因组 组件和泛基因组参考-可通过AnVIL同时获得，并通过 适当的国际数据库。我们将通过创建一套泛基因组的核心， 功能注释，主要关注基因。使用和迁移到建议的 泛基因组参考直截了当，我们将促进新的和更新的工具的创建。我们的战略 通过与工具开发人员合作来利用社区，特别是建立和促进交流 格式和创建基准，以促进最佳的社区方法。