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

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The Distributed Annotation System (DAS) has for a long time been the workhorse for integration of external data sources into Ensembl. The UCSC Genome Browser has developed and switched to the more modern and efficient 'TrackHub' technology. Ensembl now provides preliminary support for TrackHubs as well. A particular challenge is the up-to-date integration of mass spectrometry (MS)-based proteomics information, due to the use of different search databases in different labs, and regular updates in genome assemblies. However, there is the potential for huge benefits from high-quality proteogenomics integration: e.g. reliable identification of isoforms, post-translational modifications (PTMs) and quantitative protein expression information are prominent examples. The UK-based PRIDE database is one of the major resources for MS data worldwide, as well as a major driver in the international ProteomeXchange (PX) consortium.
In this project, we will provide an integrated proteogenomics infrastructure to vastly improve the current situation. We will improve TrackHub support for Ensembl, demonstrating its usefulness and performance through the complex use case of proteogenomics. This project will involve massively parallel re-analysis of MS data as new genome builds are released, via the "ProteoAnnotator" pipeline. The reprocessing of the proteomics data sets will be done at different levels: peptide/protein identification, quantification (using spectral counting), identification aimed at improving genome annotation and unrestricted search of PTMs. The reanalysed data sets will be sourced from the PRIDE repository (as part of the PX consortium), as well as from existing BBSRC-funded proteogenomics projects, and will be mapped onto Ensembl. We will focus on human and model organisms represented in Ensembl and Ensembl Genomes, like mouse, rat and Arabidopsis, and eukaryotic pathogens such as Toxoplasma, Plasmodium and Trypanosoma.

The direct beneficiaries include:

- Software vendors or pharmaceutical research and development teams, since we envisage they may wish to take up our software for local pipelines. It is important to highlight that all the software developed in the context of "ProteoGenomics" will be open-source using the Apache 2.0 licence.
- Research councils and charities funding research will benefit through the potential for increased impact of the mass spectrometry (MS)-based proteomics projects they fund, since the envisioned integration of proteomics data in Ensembl constitutes an important step forward for the field. In addition, there will be a higher incentive for public data deposition in the proteomics field due to the increased visibility of proteomics data in Ensembl.
- As proteomics is a key technology in the Life Sciences, there is the potential for considerable indirect benefits as "ProteoGenomics" will integrate proteomics information at the genome level. These benefits could be realised in any area of basic biology, biomedical or clinical science. For instance, through the reprocessing of datasets, it will be possible to find new post-translational modifications (PTMs) or genome features such as e.g. new exon-intron boundaries or DNA variation information.

Staff employed will benefit:
- Training in two key enabling technologies for the BBSRC (genomics and proteomics) and exposure to new collaborations.