ProteoGenomics: Dynamic Linkage of Genomes and Proteomes through Ensembl and ProteomeXchange

对于生命科学的研究人员来说，当务之急是他们能够通过互联网以一种高效和用户友好的方式访问和查看人类基因组，以及模式生物和人类病原体的基因组。基因组本身带有关于基因位置和功能的信息注释，以及基因组中基因和其他元素的定量数据。英国的Ensembl项目是一个领先的基因组浏览器，每天有成千上万的研究人员使用。当基因组信息与其他生物数据源（如蛋白质组学）集成并可以直接查看时，它的价值将大大增加。蛋白质组学是一套致力于鉴定和定量蛋白质的技术，每个基因编码的功能分子。从技术角度来看，现代生物数据集的庞大规模使得将它们有效地整合到基因组浏览器中具有挑战性。一种称为DAS（分布式注释系统）的技术是基因组浏览器用于集成外部数据的流行技术，但它不再支持急需的新功能或扩展到现代数据集的大小。另一个基因组浏览器，UCSC基因组浏览器，开发了一种更现代、更高效的技术，专门为大规模数据集设计，称为“TrackHubs”。UCSC和Ensembl都已经开发了对这项技术的初步支持，但对许多用户来说仍然存在限制，而Ensembl的支持仍然不完整。在“ProteoGenomics”项目中，我们首先希望进一步发展“TrackHub”技术，扩大其在Ensembl中的使用范围，并使世界各地的研究人员更容易发现和使用包含不同类型研究数据的TrackHub。Ensembl的TrackHub技术将首次扩展到蛋白质组学数据，从而改善非基因组学生物信息在这一广泛使用的资源中的提供。在这个项目中，我们将构建一种技术，以动态和有效的方式将蛋白质组学数据与Ensembl中保存的基因组数据集成在一起。考虑到这一目标，我们将使用在世界上一个主要存储库中提交和可用的公开MS蛋白质组学数据，英国的资源PRIDE，也是蛋白质组学资源ProteomeXchange联盟的领导者之一。我们将通过ProteoAnnotator管道重新分析PRIDE中的数据，为生成数据的研究团队最初提交的结果提供更新或补充信息。我们正在开拓从相同数据中提取更多价值的技术，以了解蛋白质在丰度上的变化以及蛋白质上发生的化学修饰，改变它们的功能，这两种结果通常是研究小组向PRIDE提交数据时最初不会产生的。通过这种数据重用和提取新的生物学发现，提交的数据集的价值将会增加。此外，“ProteoGenomics”将为最近启动的人类蛋白质组计划（Human Proteome Project， HPP）的数据集提供门户，为全球研究界提供这些数据集的单一入口点。

For researchers in the Life Sciences, it imperative that they are able to access and view the human genome, and genomes of model organisms and human pathogens in an efficient and user-friendly way via the Internet. The genome itself is annotated with information about the locations and functions of genes, and quantitative data about genes and other elements within the genome. The UK-based Ensembl project is a leading genome browser, used by thousands of researchers every day. The value of genomic information is greatly increased when it is integrated with and can be directly viewed alongside other biological data sources such as proteomics - a set of technologies devoted to the identification and quantification of proteins, the functional molecules encoded by each gene. From a technical point of view, the large size of modern biological data sets makes it challenging to efficiently integrate them into genome browsers. A technology called DAS (Distributed Annotation System) is the prevalent technology used by genome browsers to integrate external data but it can no longer support much-needed new features or scale to the sizes of modern data sets. Another genome browser, the UCSC Genome Browser, has developed a more modern and efficient technology, specifically designed for large-scale data sets called 'TrackHubs'. Both UCSC and Ensembl have developed initial support for this technology, but there are still limitations for many users, and Ensembl's support remains incomplete. In the 'ProteoGenomics' project, we first want to further develop the 'TrackHub' technology, expanding its scope of usage in Ensembl, and making it easier for researchers around the world to discover and use TrackHubs containing different types of research data. Ensembl's TrackHub technology will be expanded to proteomics data for the first time and thus improve the provision of non-genomics biological information in this widely used resource.In the project, we are going to build technology to integrate proteomics data with the genome data held in Ensembl, in a dynamic and effective way. With this aim in mind we will use public MS proteomics data submitted and available in one of the main repositories in the world, the UK-based resource PRIDE, which is also one leading the ProteomeXchange Consortium of proteomics resources. We will reanalyse the data in PRIDE via our ProteoAnnotator pipeline to provide updated or complementary information to the results originally submitted by the research team that generated the data. We are pioneering techniques for extracting more value from the same data, to understand how proteins vary in their abundance and in chemical modifications that occur on proteins, altering their function, two types of results often not generated initially by research groups submitting data to PRIDE. Through this data reuse and the extraction of new biological findings, the value of the submitted datasets will increase. In addition, 'ProteoGenomics' will provide a portal for datasets from the recently started Human Proteome Project (HPP), providing the global research community with a single entry point to these datasets.