DiseaseNetMiner - A novel tool for mining integrated biological networks of host and pathogen interaction

现代社会正日益受到大量微小真菌病原体的威胁，这些病原体会导致农业和园艺作物以及养殖动物的疾病。其中许多疾病对全球和当地的粮食安全造成重大、有害的影响。此外，有一种令人担忧的趋势，即病原体对宿主的攻击性变得更强，导致更多的疾病(毒力增加)，以及经常用于控制真菌病原体爆发的抗真菌化学品(称为杀菌剂)变得不那么有效。在最近的过去，(在基因组学时代)，科学家们开发了对生物体的所有染色体进行排序和组装并预测基因含量的技术(即获得它们的完整基因组蓝图)。现在，在后基因组时代，下一代测序技术已经发展起来，这导致了更多的基因组数据的爆炸性增长，以及丰富的基因表达、蛋白质表达、遗传和生物学数据，科学家们使用这些数据来描述病原体-宿主相互作用的表型和疾病结果。然而，对于许多在生物学、生物化学或遗传学方面有专长的科学家来说，这种“组学”数据爆炸往往被视为一种负担，“一个质量各异的无限数据汤”，只有那些拥有基于专业计算的解释技能(称为生物信息学)、但往往只有最低限度的专业生物学知识的人才能穿透这些数据。因此，迫切需要开发新的基于计算机的工具，使研究人员能够连接、探索和比较所有可用于致病病原物种的大小规模数据集。一旦我们完全了解真菌病原体如何致病，以及寄主物种如何试图自卫，就有可能操纵这些过程和机制，进而设计新的方法来降低疾病水平，从而改善全球粮食安全。在这个项目中，我们将开发一个新的软件工具，称为DiseaseNetMiner，它将是用户友好的，可以被许多不同类型的科学家用来探索集成的生物网络，该网络可以预测控制真菌病原体致病能力的过程。DiseaseNetMiner将从各种复杂的大规模数据输入中提供可理解的输出。DiseaseNetMiner将允许没有生物信息学专业技能的研究人员探索这些来自多个物种的丰富现有数据，并将其与他们自己的最新尖端结果进行比较，以实现快速进步和新发现。这一基本工具将有效地连接不同的数据类型，然后以一种易于操作、显示和询问的可访问、可探索和可扩展的格式返回结果。DiseaseNetMiner将创造一个新的研究环境，从中可以做出新的科学见解和生物发现。英国研究界一直处于这一领域研究和发现的前沿。我们提出的倡议将是一种非常有用和具有成本效益的方式，以确保英国研究界所展示的领导地位在未来十年继续下去。我们期待这将在我们的领域和其他领域产生巨大影响的成果，以迎接我们这个时代的重大挑战。

Modern society is increasingly under threat from a plethora of microscopic fungal pathogens, which cause diseases in agricultural and horticultural crops, and in farmed animals. Many of these diseases cause a significant, detrimental impact on global and local food security. Furthermore, there is a worrying tendency for pathogens to become more aggressive towards their hosts, to cause more disease (increased virulence) and for the anti-fungal chemicals (called fungicides) that are often used to control fungal pathogen outbreaks to become less effective. In the recent past, (during the genomics era) scientists have developed technologies to sequence and assemble all the chromosomes of an organisms and predict the gene content (i.e. obtain their complete genome blueprints). Now, in the post-genomic era, next generation sequencing technologies have been developed and this has led to an explosion of more genomic data alongside a wealth of gene expression, protein expression, genetic and biological data, which are used by scientists to describe pathogen-host interaction phenotypes and disease outcomes. However, for many scientists with expertise in biology, biochemistry or genetics, this 'omics' data explosion is often seen as a burden, 'an infinite data soup of varying qualities' that only those with specialist computing-based interpretation skills (called bioinformatics), but often only minimal specialist biological knowledge, can penetrate. Therefore, new computer based tools urgently need to be developed to allow researchers to connect, explore and compare all the large and small-scale datasets available for pathogenic species that cause diseases. Once we fully understand how fungal pathogens cause disease, and how the host species try to defend themselves, will it be possible to manipulate these processes and mechanisms and go on to devise new ways to reduce disease levels and thereby improve global food security. In this project, we will develop a novel software tool, called DiseaseNetMiner, which will be user-friendly and can be used by many different types of scientists to explore integrated biological networks that can predict processes controlling the disease-causing abilities of fungal pathogens. DiseaseNetMiner will deliver understandable outputs from diverse and complex large-scale data inputs. DiseaseNetMiner will allow researchers without specialist bioinformatics skill to explore and compare this wealth of existing data from multiple species with their own latest cutting-edge results to permit rapid progress and new discoveries. This fundamental tool will effectively connect different data types and then return the results in an accessible, explorable, as well as scalable, format that can be easily manipulated, displayed and interrogated. DiseaseNetMiner will create a novel research environment from which new scientific insights and biological discoveries can be made.The UK research community has been at the very forefront of research and discovery in this field. The initiative we propose will be an exceptionally useful and cost-effective way of ensuring that the leadership shown by the UK research community will continue in the decade ahead. We expect this to yield outcomes with huge impact in our field and beyond, to meet the grand challenges of our age.