GENCODE: comprehensive genome annotation for human and mouse

总体--项目摘要 GENCODE联盟的目标是创建一个基本的参考基因组 注释，其中识别了人类和小鼠基因组中的所有基因特征，并 根据生物证据进行高精度分类，然后发布这些 有利于生物医学研究和基因组解释的注释。GENCODE目标 为了更好地理解“正常”的人类基因组；使用最常见的基因组序列 常用的小鼠品系将有助于最有效地使用这些关键模型 大规模的基因敲除分析和疾病特异性研究。生成常规批注的步骤 高精度的版本，GENCODE将继续遵循其完善的和 保守的研究设计，辅以对新技术价值的有针对性的调查 技术、新数据和新证据来源。GENCODE专注于蛋白质编码 和非编码基因座，包括它们的选择性剪接异构体和假基因。超过了 在这项提议的过程中，GENCODE将遵循基因组学的主要方向，包括GRAPE- 基于基因组表示，长读转录组测序，连接基因和 影响其转录的相关调控区域，并识别不影响其转录的基因 出现在当前引用程序集上。GENCODE财团有四个基本原则 组件：(1)利用人工注释的综合基因注释管道；(2) 一种综合的假基因识别和分类方法；(3)一套 评估和增强基因注释的计算方法；以及(4)互补 用于验证和功能注释的实验管道。更具体地说，在接下来的四年 Years GENCODE的目标是(1)将人类和小鼠的GENCODE基因集扩大到接近 在现有实验技术的情况下尽可能完成；(2)部署以人口为基础的 基因组注释，以确保在个人人类意志中表达的任何转录本亚型 出现在参考注释集中；(3)扩展基因注释以包括核心 来自选定数据集的调节区和组织特异性增强子；(4)分发 GENCODE注释，并参与社区注释工作。时下流行 GENCODE数据的分发渠道，包括GENCODE网站、EnSembl和 UCSC Genome浏览器将得到维护。最后，确定基因优先顺序的新机制 将建立具有社区输入的手动注释，其长期目标是 建立GENCODE作为研究和临床基因组学的标准注释集 努力。

OVERALL - PROJECT SUMMARY The objective of the GENCODE consortium is to create a foundational reference genome annotation, in which all gene features in the human and mouse genomes are identified and classified with high accuracy based on biological evidence, and then to release these annotations for the benefit of biomedical research and genome interpretation. GENCODE aims for a better understanding of a `normal' human genome; using genome sequences of the most commonly used mouse strains will facilitate the most effective use of these key models for large-scale knockout analysis and disease-specific research. To produce regular annotation releases of high accuracy, GENCODE will continue to follow its well-established and conservative research design, supplemented by targeted investigations into the value of new technologies, new data and new sources of evidence. GENCODE focuses on protein-coding and non-coding loci, including their alternatively spliced isoforms and pseudogenes. Over the course of this proposal GENCODE will follow major directions in genomics, including graph- based genome representations, long-read transcriptome sequencing, connecting genes and the associated regulatory regions that affect their transcription, and identifying genes that are not present on the current reference assembly. The GENCODE consortium has four fundamental components: (1) a comprehensive gene annotation pipeline leveraging manual annotation; (2) an integrated approach to pseudogene identification and classification; (3) a set of computational methods to evaluate and enhance gene annotation; and (4) complementary experimental pipelines for validation and functional annotation. More specifically, in the next four years GENCODE aims to (1) extend the human and mouse GENCODE gene sets to as near completion as possible given current experimental technology; (2) deploy population-based genome annotation to ensure that any transcript isoform expressed in an individual human will be present in the reference annotation set; (3) extend the gene annotation to include core regulatory regions and tissue-specific enhancers from selected datasets; (4) to distribute GENCODE annotations and engage with community annotation efforts. Current popular distribution channels for GENCODE data including the GENCODE web site, the Ensembl and UCSC Genome Browsers, will be maintained. Finally, new mechanisms for prioritizing genes for manual annotation with community input will be established, with the long-term aim of establishing GENCODE as the standard annotation set for research and clinical genomics efforts.