GENCODE: comprehensive reference genome annotation for human and mouse

项目摘要 GENCODE联盟为人类和小鼠创建基本的参考基因组注释 根据生物学证据以高精度识别和分类所有特征的基因组，以及 然后免费释放，用于生物医学研究和基因组解释。GENCODE寻求 创建注释，通过优先排序来增加对人类和小鼠基因组功能的理解 人类疾病基因和尊重小鼠作为主要哺乳动物模式生物的作用。要有效地 注释基因组，GENCODE创建了一套工具，并利用其合作伙伴的深厚专业知识 跨四个基本组成部分：1)利用手册和 计算性注释；2)一套评估和增强基因注释的计算方法；3) 以在标准协议中不易检测到的表达序列为目标的实验流水线；以及4)机器 学习能力，以提高项目的各个方面。GENCODE将继续主要关注蛋白质编码 和非编码基因座，包括它们的选择性剪接异构体和假基因，将扩展Expert 手动审查小的非编码RNA(NcRNA)和非多聚腺苷化转录本的注释。 GENCODE还将把监管注释扩展到一组定义的基因相关特征，以获得更多 准确反映调控区域之间的相互联系，包括那些具有转录序列的区域 例如ncRNA，以及总的转录输出。GENCODE将利用日益成熟的 基因组学技术包括长读转录组测序、功能基因组分析和图谱分析。 基于基因组表示，以识别特征，如基因、伪基因、外显子和剪接点 不正确的、不完整的或基因组区域根本不存在于当前的参考组件中。更多 具体地说，GENCODE计划在接下来的四年里，将其人类和老鼠的基因组扩大到 在现有数据和当前实验技术的情况下尽可能完成；2)利用新的、高质量的 人类基因组组装和靶向转录数据扩大代表性，使更多的人类 单倍型将有高质量的注释3)注释基因相关的调节区，包括增强子- 启动子连接4)与其他资源协作以确保基因和 用于报告临床变异的调节特征和参考抄本；以及5)分发GENCODE 注解并参与社区注解工作，以确保准确性和一致性。主要 EnSembl和UCSC Genome浏览器以及 GENCODE网站。我们将建立新的机制，有效地开展双向外联、培训和 与社区进行沟通，长期目标是将GENCODE作为标准注释 用于研究和临床基因组学应用。

Project Summary The GENCODE consortium creates foundational reference genome annotation for the human and mouse genomes in which all features are identified and classified with high accuracy based on biological evidence, and then freely released for the benefit of biomedical research and genome interpretation. GENCODE seeks to create annotation that increases the understanding of genome function in both human and mouse by prioritizing human disease genes and respecting the role of mouse as the major mammalian model organism. To effectively annotate genomes, GENCODE has created a suite of tools and draws on deep expertise across its partners across four fundamental components: 1) a comprehensive gene annotation pipeline leveraging manual and computational annotation; 2) a set of computational methods to evaluate and enhance gene annotation; 3) experimental pipelines targeted to expressed sequences less detectable in standard protocols; and 4) a machine learning capacity to improve all facets of the project. GENCODE will maintain a major focus on protein-coding and non-coding loci, including their alternatively spliced isoforms and pseudogenes and will extend expert manual review to small non-coding RNAs (ncRNA) and the annotation of non-polyadenylated transcripts. GENCODE will also expand regulatory annotation to a defined set of gene-associated features to more accurately reflect the interconnections between regulatory regions, including those with transcribed sequences such as ncRNA, and overall transcriptional output. GENCODE will take advantage of the increasing maturity of genomics technology including long-read transcriptome sequencing, functional genomics assays, and graph- based genome representations to identify features such as genes, pseudogenes, exons and splice sites that are incorrect, incomplete or in genome regions simply not present in the current reference assembly. More specifically, in the next four years GENCODE plans to 1) extend its human and mouse gene sets to as near completion as possible given available data and current experimental technology; 2) leverage new, high-quality human genome assemblies and targeted transcriptomic data to expand representation so that more human haplotypes will have high-quality annotation 3) annotate gene-associated regulatory regions including enhancer- promoter connections 4) collaborate with other resources to ensure a consistent representation of genic and regulatory features and reference transcripts for reporting clinical variation; and 5) distribute GENCODE annotations and engage with community annotation efforts to ensure accuracy and consistency. Primary GENCODE data will continue to be available from the Ensembl and UCSC Genome Browsers and the GENCODE web site. We will develop new mechanisms for effective two-way outreach, training and communication with the community with the long-term aim of establishing GENCODE as the standard annotation set for research and clinical genomics applications.