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

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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.