GCRF-BBR: Beyond the genome: Enabling tropical livestock EWAS of infectious diseases

牛是地球仪中低收入国家经济的重要组成部分。它们是肉类和奶制品的来源，提供皮革和其他副产品，并经常被用作工作动物。牛可以在作物不易生长的地方放牧，提供粪便作为有效的肥料，并可以将饲料转化为高蛋白质食物。牛通常是低收入和中等收入国家个人拥有的最有价值的财产，但容易感染一系列传染病，这不仅给这些国家造成沉重的经济负担，而且往往还可以传染给人类。全球三分之二以上的牛种群在低收入和中等收入国家。因此，减少牛传染病的负担将对这些地区产生重大利益。然而，对于许多疾病，没有疫苗或治疗方法。在有兽医服务的地方，糟糕的兽医服务通常意味着牲畜饲养者必须自己支付疫苗和治疗费用。因此，这些疾病是摆脱贫困的主要障碍。由于病原体和牛的共同进化，有各种各样的牛品种表现出对重要传染病的天然耐受性或抗性。虽然这些品种往往生产力较低，使他们对LMIC农民的吸引力较低，如果他们的阻力的机制可以确定和利用，然后品种更高的生产力和耐受性可能是developed.The本项目的目的是发展的框架，使识别基因组区域与耐受性/抗性通过表观基因组关联研究（EWAS）。表观基因组的差异，即覆盖基因组的化学修饰，通过与基因调控的关联与表型相关联。通过比较耐受和易感动物的表观基因组，有可能确定与抗病性相关的区域。然而，目前我们甚至缺乏关于LMIC牛品种表观基因组的基线信息，以及进行基于血液的EWAS的工具和资源。特别是，由于血液样品是各种细胞类型的复合物，每种细胞类型具有不同的表观基因组谱，因此有必要将与疾病耐受性相关的任何表观遗传改变与纯粹由样品之间细胞类型组成的变化引起的差异分开。我们将通过生成LMIC中流行的两个主要牛亚种的主要免疫细胞类型的表观基因组图谱来解决这个问题。利用这一资源，我们将创建一个门户网站，使用户能够估计其样品中的细胞类型组成，使下游EWAS不受样品组成变化的干扰，提供更大的能力来识别与传染病相关的真正表观基因组差异。

Cattle are a vital component of the economies of low and middle income countries across the globe. They are a source of meat and dairy products, provide leather and other by-products and are often used as working animals. Cattle can be grazed where crops are not easily grown, provide manure as effective fertiliser and can convert forage into high-protein food. Often cattle are the most valuable possession individuals in low and middle income countries own, but are susceptible to a range of infectious diseases, which not only inflict a heavy economic burden on these countries but can also often be transmissible to humans.Over two-thirds of the global cattle population are in low and middle income countries. Reducing the burden of cattle infectious diseases would consequently have major benefits to these areas. However for many diseases no vaccine or treatment is available. Where they are available, poor veterinary services generally mean the livestock keepers must pay for vaccines and treatments themselves. Consequently these diseases are major barriers to escaping poverty. Due to the co-evolution of pathogens and cattle there are various examples of cattle breeds that show natural tolerance or resistance to important infectious diseases. Although these breeds are often less productive, making them less attractive to LMIC farmers, if the mechanisms underlying their resistance could be identified and harnessed, then breeds of both higher productivity and tolerance could potentially be developed.The aim of this project is to develop the framework to enable the identification of genomic regions linked to tolerance/resistance via epigenome-wide association studies (EWAS). Differences in the epigenome, chemical modifications that overlay the genome, are linked to phenotypes through their association with gene regulation. By comparing the epigenomes of tolerant and susceptible animals it is possible to determine regions linked to disease resistance. However, at present we lack even baseline information on the epigenomes of LMIC cattle breeds, and the tools and resources for undertaking blood-based EWAS. In particular, as blood samples are a composite of various cell types, each with a distinct epigenome profile, it is necessary to disentangle any epigenetic alterations linked to disease tolerance from differences resulting purely from variation in cell-type composition between samples. We will address this by generating an epigenome atlas of major immune cell types across the two major sub-species of cattle prevalent in LMICs. Using this resource we will create a web portal to enable users to estimate the cell-type composition in their samples, allowing downstream EWAS not confounded by between sample composition variations, providing a greater ability to identify true epigenome differences linked to infectious diseases.