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.

项目摘要（项目1：维护，改善和提供人类参考） 我们建议将最佳当前方法和实践与实用，可扩展的模型相结合以创建 并共享一个基于组件的广泛有用的泛 - 人类基因组参考（“泛基因组”） 原始数据由基因组生产中心提供。我们提出的泛基因组参考并非完全 替换现有的GRCH38参考 这结合了人类遗传多样性的丰富代表。为了实现这个计划，我们有 组建了一群拥有完整专业知识的人，将共同构建，分享， 维护和改善最先进的人类泛基因组资源。转换初始基因组 组合成高质量的人类基因组参考队列，我们​​将执行组装质量控制， 错误纠正和验证，反映了我们为维护和 改善现有的人类参考基因组。为了使这个集合的集合可比，我们将 然后创建一张全面的基因组变体图。使用人类基因组 参考队列和变异图，我们将创建一个具有三个的人类泛基因组参考 完全和必不可少的部分：（i）编码非冗余基因组的序列图 通过将共享序列合并在一起的方式； （ii）序列中单倍型的可搜索编码 图，图本身不会捕获的东西； （iii）使它成为可能的坐标系 在与GRCH38的向后兼容时，同时指的是所有变化。构建此图 我们将使用我们开发的工具并在整个社区中使用的工具来测试和原型方法， 释放稳定和版本的泛基因组参考。我们还提出了一个计划，以处理来自 财团和更广泛的社区，并通过数据分析，策划和 目标测序。我们将遵循一个完全开放的模型，以确保所有数据 - 主要数据，基因组 组件和泛基因组参考 - 简单可通过砧座提供，并通过 适当的国际数据库。我们将通过创建核心集合组来为此资源增加价值 功能注释，主要集中在基因上。使工作并迁移到拟议的 Pan-Genome参考直接，我们将促进创建新的和更新的工具。我们的策略 通过与工具开发人员合作，特别是建立和促进交流来利用社区 格式并创建基准以促进最好的社区方法。