Establishing the infrastructure for functional annotation of farmed animal genomes

对驯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善，改善动物健康和福利，有助于医学研究和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（“构成生物体遗传物质的DNA核苷酸序列”）为发现遗传变异提供了一个重要框架基因型（“基因型”）与动物特征（“表型”）的变异相关。基因组序列可用于许多家养动物，包括家禽（鸡、火鸡和鸭）、家畜（牛、猪、山羊和绵羊）、鱼类（鳕鱼、罗非鱼和鲑鱼）和伴侣动物（狗和马）。今天的DNA测序技术既快速又相对便宜，并且允许开发基于产生短或长序列的广泛测定。高质量的注释基因组对于这些分析至关重要，包括细胞RNA的RNA-seq分析（“读取基因组，编码信息以合成蛋白质或调节基因表达”），基因组共价修饰（甲基基团）位置的Methyl-seq分析或与基因组结合的蛋白质的ChIP-seq分析，激活或抑制基因表达。鉴定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是必不可少的。我们已经使用Ensembl系统建立高质量的注释的动物基因组的基础上，主要是cDNA和比较数据从其他物种。虽然70-90%的蛋白质编码元件可以被鉴定，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、小鼠和驯养动物基因组中的基因读取的注释RNA的数量表明，驯养动物中RNA的复杂性被低估了。更少的是已知的调控序列，这是一个重大的障碍，了解基因型和表型之间的联系。这一挑战的重要性是由欧盟-美国动物生物技术工作组，这是促进需要跨国协调功能注释的动物基因组认识。2014年，在圣地亚哥举办了一个由100多名科学家参加的研讨会之后，一个国际联盟发起了“ANEARLY基因组功能注释或FAANG”。FAANG项目旨在为全面注释驯养动物基因组提供实验数据。我们将建立支持这些目标的数据基础设施。该基础设施将包括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，并进行质量控制检查。DAC将寻求最大限度地减少数据的冗余分析。将开发用于序列分析数据质量控制的标准生物信息学管道（ChIP-Seq、RNA-Seq和Methyl-seq）、用于验证样品身份的工具和许多主要分析管道（用于绘制蛋白质编码/非编码RNA和调控特征的RNA位置）。高质量注释基因组是信息的关键来源，对当代生物科学研究至关重要。它不仅对学术研究人员有价值，而且对动物育种，动物健康和制药行业的科学家也有价值。该项目涉及提供高质量注释参考基因组的基础设施，以使对经济重要动物的研究成为可能。

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.