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

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The types and sites of post-translational modifications (PTMs) on proteins are rich and diverse, providing cells with a rapid mechanism for adapting function under different conditions. PTMs are widely studied across all areas of fundamental and applied life sciences research. Proteomics approaches using mass spectrometry (MS) provide the sole high-throughput means to detect and localize protein PTMs. Despite their biological importance, PTM-relevant data is collated in the public domain via disparate resources, with a lack of data provenance. An efficient way to improve the situation is to make PTM information derived from proteomics approaches available through UniProtKB (http://www.uniprot.org/), the world-leading protein-knowledgebase. There are hundreds of relevant PTM proteomics datasets in the public domain since the proteomics community is now widely embracing open data policies (e.g. through the resources PRIDE and PeptideAtlas, part of the ProteomeXchange consortium).
We will develop and deploy in the cloud open and reproducible pipelines to re-analyse consistently hundreds of PTM relevant public datasets coming from human and the main model organisms. Complementary analysis approaches will be used: primarily standard protein database-based but also spectral library-based and open modification searches. Special attention will be devoted to ensuring that PTM localization is accurate and community guidelines will be developed with that goal in mind. These data will be widely disseminated to UniProtKB and other knowledge-bases (e.g. neXtProt) and made available at PRIDE, PeptideAtlas, and a new resource PTMeXchange. These new PTM data will be integrated across studies, to increase statistical power at an unprecedented scale and accuracy. Finally, we will perform several following demonstration studies to understand PTM motifs, function and evolution.

There is the potential for the following impacts:

- The biggest potential impact is on Pharma, within which there are many efforts in drug design to target cell signalling, and PTMs. The results will inevitably feed into improved understanding of processes and potentially generating new targets. There is also potential for indirect benefits in the biotech industry (improved understanding of PTMs in fungi) and Agrifood (PTMs on plants), e.g. derived through inference of site conservation from model organisms.

- Software vendors or pharmaceutical research and development teams will benefit, since we envisage they may wish to take up our software for local pipelines (e.g. deployed in their own cloud environments). It is important to highlight that all the software developed during the proposal will be open source.

- Research councils and charities funding research will benefit through the potential for increased impact of the mass spectrometry (MS)-based proteomics projects they fund, thanks to the re-analysis of public proteomics datasets and the integration of novel PTM proteomics data in UniProtKB.

- More broadly, as proteomics is a key technology in the Life Sciences, there is the potential for considerable indirect benefits across a wide range of areas in basic biology, biomedical and clinical science, as more value will be derived from datasets.

- Life scientists worldwide will be able to benefit from the training activities planned (both face-to-face and via on-line resources).

Staff employed will benefit:

- Further training in one key enabling technology for the BBSRC (proteomics) and exposure to a multi-disciplinary team, and to conferences, workshops and new national and International collaborations.

- Acquire skills needed to work with bioinformatics software in a cloud environment, something that is getting increasingly important with the growing size of datasets and the need of suitable IT infrastructure. The team will also use cutting edge machine learning methods in WP4, which are skills hugely in demand in academic research and industry.