Establishing the infrastructure for functional annotation of farmed animal genomes

对家养动物的研究具有重要的社会经济影响，包括支持和加速农业的改进，改善动物的健康和福利，促进医学研究，并增加我们对自然和野生动物种群的了解。高质量的注释基因组序列(组成生物体遗传物质的DNA核苷酸序列)为发现该序列中与动物特征(表型)变化有关的遗传变异(“基因”)提供了重要的框架。许多家养动物的基因组序列是可用的，包括家禽(鸡、火鸡和鸭子)、家畜(牛、猪、山羊和绵羊)、鱼(鳕鱼、罗非鱼和三文鱼)以及同伴动物(狗和马)。今天，DNA测序技术既快速又相对便宜，并允许开发基于产生短序列或长序列的广泛分析。高质量的带注释的基因组对于这些分析至关重要，包括对细胞RNA的RNA-SEQ分析(“读出基因组，编码合成蛋白质或调节基因表达的信息”)，对基因组的共价修饰(甲基团)位置的甲基-序列分析，或对激活或抑制基因表达的与基因组结合的蛋白质的芯片-序列分析。识别基因组中编码蛋白质、非编码RNA或调节基因表达的功能元件，对于理解基因组中编码的表型结果至关重要。注释的基因组序列可以通过EnSembl、NCBI和UCSC在线免费获得。我们已经使用EnSembl系统建立了高质量的动物基因组注释，主要基于cdna和其他物种的比较数据。虽然70%-90%的蛋白质编码元件可以被识别，但关于非编码RNA基因的信息很少，其中许多被怀疑调节基因表达。比较从人类、小鼠和家养动物基因组中读取的带注释的RNA的数量表明，家养动物中RNA的复杂性被低估了。对调控序列的了解更少，这是理解基因和表型之间联系的一个重要障碍。这一挑战的重要性得到了欧盟-美国动物生物技术工作组的认识，该工作组正在推动对动物基因组进行跨国协调功能注释的必要性。继一个由100多名科学家参加的圣地亚哥研讨会(2014年)之后，一个国际联盟发起了“动物基因组的功能注释”。FAANG项目旨在为全面注释驯化动物基因组提供实验数据。我们将建立数据基础设施来支持这些目标。基础设施将包括Roslin/TGAC/EMBL-EBI的硬件和计算能力，以及能够对动物基因组进行功能注释的软件。该基础设施将支持数据协调中心和数据分析中心。DCC将存储来自FAANG财团的数据和分析，并接受质量控制检查。DACS将寻求最大限度地减少数据的冗余分析。将开发用于逐个序列分析数据的质量控制的标准生物信息学管道(ChIP-Seq、RNA-Seq和甲基-Seq)、确认样本身份的工具和一些主要分析管道(绘制蛋白质编码/非编码RNA和调控特征的RNA的位置图)。高质量的注释基因组是关键的信息来源，对生物科学的当代研究至关重要。它不仅对学术研究人员有价值，而且对在动物育种、动物健康和制药行业工作的科学家也有价值。该项目涉及提供高质量的带注释的参考基因组的基础设施，以便能够对经济上重要的动物进行研究。

Research on domesticated animals has important socio-economic impacts, including underpinning and accelerating improvements in agriculture, improving animal health and welfare, contributing to medical research and increasing our understanding of natural and wild animal populations.High quality annotated genome sequences ("sequence of DNA nucleotides that make up the genetic material of an organism") provide an important framework for the discovery of genetic variation ("genotype") in that sequence linked to variation in the characteristics ("phenotype") of an animal. Genome sequences are available for many domesticated animals, including poultry (chicken, turkey and duck), livestock (cattle, pig, goat and sheep), fish (cod, tilapia and salmon) and companion animals (dog and horse). Today technology to sequence DNA is both rapid and relatively cheap and allowed the development of a wide range of assays based on generating short or long sequences. High quality, annotated genomes are critical to the analysis of these assays, including RNA-seq analysis of a cells RNA ("read off the genome, encoding information to synthesise proteins or regulate gene expression"), Methyl-seq analysis of the location of covalent modifications (methyl-groups) to the genome or ChIP-seq analysis of proteins bound to the genome that activate or repress gene expression. Identifying the functional elements within the genome that code for proteins, non-coding RNAs or regulate gene expression is essential for understanding the phenotypic consequences encoded in the genome.Annotated genome sequences are freely available on-line through Ensembl, NCBI and UCSC. We have used the Ensembl system to establish high quality annotations of animal genomes based on mostly cDNA and comparative data from other species. Whilst 70-90% of protein coding elements can be identified, there is little information on non-coding RNA genes many of which are suspected to regulate gene expression. Comparing the number of annotated RNAs read from genes in the human, mouse and domesticated animal genomes shows that the complexity of RNAs in domesticated animals is underestimated. Even less is known of regulatory sequences, which is a significant barrier to understanding the link between genotype and phenotype.The importance of this challenge is recognised by the EU-US Animal Biotechnology Working Group, which is promoting the need for transnational coordinated functional annotation of animal genomes. Following a workshop of over 100 scientists in San Diego (2014) an international consortium the "Functional Annotation of ANimal Genomes or FAANG" was launched. The FAANG project aims to provide experimental data to comprehensively annotate domesticated animal genomes.We will establish the data infrastructure to support these goals. The infrastructure will comprise hardware and compute capacity at Roslin/TGAC/EMBL-EBI together with software to enable the functional annotation of animal genomes. The infrastructure will support a Data Coordination Centre (DCC) and Data Analysis Centres (DACs). DCC will store data and analyses from the FAANG consortium subject to quality control checks. DACs will seek to minimise redundant analysis of data. Standard bioinformatics pipelines for quality control of assay-by-sequence data (ChIP-Seq, RNA-Seq, and Methyl-seq), tools for validation of sample identity and a number of primary analysis pipelines (to map location of RNAs for protein coding/non-coding RNAs and regulatory features) will be developed.A high quality annotated genome is a key source of information and critical for contemporary research in the biological sciences. It is valuable not only to academic researchers, but also to scientists working in animal breeding, animal health and pharmaceutical industries. This project is concerned with the infrastructure for delivering high quality annotated reference genomes to enable research on economically important animals.