BBSRC-NSF/BIO PTMeXchange: Globally harmonized re-analysis and sharing of data on post-translational modifications

蛋白质是细胞中的关键功能分子，执行多种生物任务。这包括催化反应，为细胞成分提供结构，不同细胞之间的信号传递以及调节其他基因的产生。蛋白质是由单个氨基酸链组成的，这些氨基酸链最初形成一个长序列，形成一个严格控制的3D结构，赋予每种蛋白质高度特异性的功能。基因组测序的出现将我们研究这些分子的能力转变为“大数据”学科，再加上质谱分析和相关计算技术的进步。“组学”的这个特殊分支被称为蛋白质组学——对给定生物样本中可以检测到的所有蛋白质进行高通量研究（鉴定和定量）。蛋白质组学在生物学和生物医学研究中被广泛用于分析系统，如人类、模式生物（包括植物）和传染病/微生物等。许多生物功能依赖于蛋白质可以经历的化学修饰，称为翻译后修饰（PTMs）。由于PTMs的发生，一个特定的基因可以产生大量不同的蛋白质实体，这些蛋白质实体可能具有不同的生物学功能。PTMs可以提供一种快速改变功能的机制，例如开关酶（生物催化剂）的“开启”和“关闭”。由于其重要的功能，蛋白质上的ptm位点经常成为药物设计的靶点，特别是抗癌药物。在这项资助中，我们将使用高质量的数据分析管道，在公共领域的数百个蛋白质组学数据集中研究主要类型的ptm的发生，涉及人类和主要模式生物（例如小鼠，大鼠和模式植物拟南芥）。本项目涉及三个世界领先的生物信息学资源，分别是PRIDE和PeptideAtlas（蛋白质组学资源），以及UniProtKB（蛋白质知识库）。我们期望UniProtKB将成为向不同学科的数千名研究人员传播项目成果的主要资源。我们还将展示将产生的大量数据的可能的研究应用，例如研究ptm如何在不同的物种群体中进化。我们会透过不同的培训和外展活动，包括举办工作坊、培训和网上辅导/教程，确保计划的所有成果得到传播。

Proteins are the key functional molecules in cells, performing multiple biological tasks. This includes catalysing reactions, providing structure to cellular components, signaling between different cells and regulating the production of other genes among many others. Proteins are composed of chains of individual amino acids that are formed initially into a long sequence, which forms into a strictly controlled 3D structure, giving the highly specific function to each protein. The advent of genome sequencing has transformed our ability to study these molecules into a "Big Data" discipline, coupled to advances in mass spectrometry and allied computing techniques. This particular branch of "'omics" is referred to as proteomics - the high-throughput study (identification and quantification) of all the proteins that can be detected in a given biological sample. Proteomics is used right across biological and biomedical research for profiling systems as varied as human, model organisms including plants, and infectious diseases/microbes, among many others. Many biological functions are dependent on chemical modifications that proteins can undergo, called Post-translational Modifications (PTMs). Due to the occurrence of PTMs, one particular gene can produce a great number of different protein entities which can potentially have different biological functions. PTMs can provide a rapid mechanism for changing function, such as switching an enzyme (biological catalyst) "on" and "off". Due to their functional importance, sites of PTMs on proteins are frequently the targets for drug design, particularly against cancer. In this grant, we will study, using high-quality data analysis pipelines, the occurrence of the main types of PTMs across hundreds of proteomics datasets in the public domain, involving human and the main model organisms (e.g. mouse, rat and the model plant Arabidopsis). Three world-leading bioinformatics resources are involved in this proposal, namely PRIDE and PeptideAtlas (proteomics resources), and UniProtKB (protein knowledge-base). We expect that UniProtKB will be the main resource to disseminate the outputs of the project to thousands of researchers, working in varied disciplines. We will also showcase possible research applications of this huge amount of data that will be generated, for example studying how PTMs have evolved in different groups of species. We will ensure that all the outputs of the project are disseminated via different training and outreach activities, including e.g. delivering workshops, training and online help/tutorials.