3D-Proteomics: FAIRification of proteomics data for comprehensive integration with structural biology information

蛋白质是存在于所有生物体中的分子，它们提供细胞结构并执行细胞中大多数重要功能，包括催化（引起或加速）化学反应和不同细胞之间的信号传递。蛋白质组学是对特定生物样本（如细胞或细菌、植物或人类等有机体）中全部蛋白质的研究。由于蛋白质对许多关键功能至关重要，蛋白质组学可以告诉我们很多关于生物体如何工作以及疾病发生的情况，以及帮助确定潜在的治疗方法。这意味着蛋白质组学被用于许多有益的生物和生物医学研究领域。目前用于蛋白质组学的主要技术是一种叫做质谱（MS）的技术，其工作原理是将蛋白质分解成小片段，对它们进行分类，然后报告它们的质量。然后可以使用不同的软件工具来确定蛋白质的数量和特性。蛋白质的结构也非常重要，因为蛋白质通过折叠组织的方式将有助于它完成它的工作。这种结构还决定了它如何能够与其他蛋白质相互作用，例如，在细胞周围运输另一种蛋白质的蛋白质需要有一个特定的部分与它结合。蛋白质结构可以用x射线晶体学等技术来研究，这种技术利用了不同结构衍射x射线的方式。最近的一项发展被称为交联质谱（CL-MS），它是一种强大的工具，可以可视化蛋白质是如何折叠和结合的，它通过在被称为交联剂的特殊化学试剂连接的蛋白质上运行质谱来工作。不幸的是，CL-MS还没有协调成熟的开放标准，现有的数据集也不能很好地与蛋白质结构的其他信息联系起来。这意味着很难比较和整合研究小组之间的发现，而且可能会遗漏重要的知识。重要的是，蛋白质组学数据库遵循FAIR原则，易于查找（Findable），免费和开源（Accessible），易于共享和处理（Interoperable）和可重用。我们的研究小组管理着两个世界领先的数据库：蛋白质组学鉴定数据库（PRIDE），这是使用MS生成的蛋白质组学数据的存储库，以及蛋白质数据库（PDB），这是大分子（包括蛋白质）的3D结构数据的家。该项目将这些工具与我们在CL-MS方面的专业知识相结合，以开发FAIR数据标准和软件，以便使用CL-MS生成的蛋白质组学数据具有通用格式和处理管道，并提供一套软件工具，以便自由轻松地处理和分析数据。PRIDE将扩展到包括这些标准化的CL-MS数据格式，并将提供用于数据沉积和可视化的关键软件工具。重点是，我们将在PRIDE和PDB之间建立链接，以便对结构数据进行联合检查，包括PDB和PRIDE提交系统之间的集成。这将意味着科学家将能够更容易地分析蛋白质，并确定他们的研究与其他项目之间的联系，即使他们自己无法使用CL-MS设备。该项目将产生的工具和标准将使广泛的生物学和生物医学领域的研究人员受益，并将提供蛋白质组学和结构生物学信息之间的接口，这将增强和连接研究成果。该软件将确保重要的和新颖的结构蛋白质组学数据是可访问和可找到的，并且该标准将保持其互操作性和可重用性。我们将确保我们的工作得到广泛传播，我们将举办讲习班，培训和协助研究人员充分利用这些宝贵的资源。

Proteins are molecules found in all living organisms that provide structure and carry out most of the important functions in a cell, including catalysing (causing or speeding up) chemical reactions and signalling between different cells. Proteomics is the study of the entire set of proteins in a given biological sample such as a cell or an organism like a bacteria, plant or human. Since proteins are essential for so many crucial functions, proteomics can tell us a lot about how organisms work and also about what happens in illnesses, as well as helping to identify potential treatments. This means that proteomics is used across many areas of beneficial biological and biomedical research.Currently the primary technology used in proteomics is a technique called mass spectrometry (MS), which works by breaking up a protein into small fragments, sorting them and then reporting their mass. The quantity and identity of the protein can then be determined using different software tools. The structure of a protein is also very important, as the way that a protein is organised via folding will help it to carry out its job. The structure also determines how it is able to interact with other proteins, for example a protein that transports another protein around a cell needs to have a part that binds to it specifically. Protein structure can be studied using techniques like x-ray crystallography, which makes use of the way that different structures diffract (bend) x-rays. A more recent development called cross-linking MS (CL-MS) is a powerful tool for visualising how proteins fold and join together, and it works by running MS on proteins that are linked by specialised chemical reagents called cross-linkers. Unfortunately, CL-MS does not yet have coordinated mature open standards and existing datasets are not well linked to other information about protein structure. This means that it is difficult to compare and integrate findings between research groups and that important knowledge may be missed.It is important that proteomics databases follow the FAIR principles of being easy to find (Findable), free and open source (Accessible), easily shared and processed (Interoperable) and Reusable. Our research groups manage two world-leading databases: the PRoteomics IDEntifications database (PRIDE), which is a repository for proteomics data generated using MS, and the Protein Data Bank (PDB), which is home to 3D structural data for large molecules including proteins. This project will combine these tools with our expertise in CL-MS in order to develop FAIR data standards and software so that proteomics data generated using CL-MS has a common format and processing pipeline, and so that a suite of software tools is made available in order to process and analyse the data freely and easily. PRIDE will be extended to include these standardised CL-MS data formats, and key software tools for data deposition and visualisation will be made available. As a key point, we will create links between PRIDE and PDB in order to allow for joined-up examination of structural data, including integration between the PDB and PRIDE submission systems. This will mean that researchers will be able to more easily analyse proteins and identify links between their research and other projects, even if they don't have access to CL-MS equipment themselves.The tools and standards that will be generated by this project will benefit researchers across a wide range of biological and biomedical fields, and will provide an interface between proteomics and structural biology information that will enhance and connect research findings. The software will ensure that important and novel structural proteomics data are made accessible and findable, and the standards will maintain its interoperability and reusability. We will make sure that our work is disseminated widely and we will deliver workshops to train and assist researchers in making full use of these valuable resources.