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European Proteomics Infrastructure Consortium providing Access

Periodic Reporting for period 1 - EPIC-XS (European Proteomics Infrastructure Consortium providing Access)

Reporting period: 2019-01-01 to 2020-06-30

The European Proteomics Infrastructure Consortium - Providing Access (EPIC-XS) partnership is a project funded by the European Union’s Horizon 2020 program to provide access to proteomics expertise and mass spectrometry technology to all researchers within the life sciences. It brings together eighteen proteomics institutes and core laboratories, spread across fourteen European countries, with the objective to provide over 2,400 days of access to high-end proteomics technologies. This initiative will also organize various workshops and training courses open for researchers in the EU.
The four collaborative cutting-edge Joint Research Activities (JRAs) of this project are built on the strong innovative track-record of the consortium members involved and are focused on designing novel approaches for future developmental efforts to be applied in computational, translational as well as structural and spatial proteomics.
The main results of the EPIC-XS project, since the project started on January 1st 2019 are listed below. The project website (epic-xs.eu) provides comprehensive information about the goals of the project, publications, protocols, and the partners involved.
Progress from the four collaborative cutting-edge Joint Research Activities.

JRA1: Computational proteomics and cross-omics integration
This JRA manages and improves processes and data manipulation for datasets generated by all other JRAs.

Progress:
•Improved fragmentation spectrum prediction tools, subsequently proven to function as enhancements to existing DDA and DIA protein identification pipelines.
•Algorithm to assist the accurate determination of the ion masses. The FLASHDeconv algorithm (http://www.openms.org/flashdeconv) is implemented as a part of the open-source software OpenMS.
•Optimization of the MS2PIP algorithm by VIB and Prosit by TUM, which are core tools in increasing the performance and reliability of DDA and DIA acquisition approaches towards supporting robust single-cell proteomics (JRA 2).
•Development of rigorous QC assessment for clinical proteomics projects (JRA 3) via the QCloud package has been improved dramatically.
•Partner EKUT has developed a novel and more sensitive protein-protein cross-linking method (OpenPepXL, https://www.openms.de/comp/openpepxl which yields higher sensitivity for cross-linked peptides through an exhaustive (and more costly) search of the full quadratic search space.

JRA2: Future and emerging proteomics technologies

Progress:
•First time accurate detection of the mass of very large assemblies and estimate the stoichiometry of highly complex protein assemblies like virus capsids.
•Combination of mass photometry with top-down/native mass spectrometry has provided insight into highly heterogeneous samples with tens to hundreds of molecular forms of a protein that arise from a specific gene.
•Development, optimization, and application of cutting-edge MS methodologies which facilitate the study of emergent and obscure post-translational modifications (PTMs).
•A new experimental protocol that allows for the identification of proteins on total DNA for bulk chromatome profiling and de novo identification of chromatin-bound proteins in a simple, robust, and unbiased manner.
•Insight into the proteomic landscape of cancers in particular colorectal cancer and its correlation with other omics layers.
•Improvement of standard operating procedures, sample prep, improved online separation methods have been employed to study the effects of antibiotic resistance.
•Hybrid approaches, including cross-linking MS and native mass spectrometry to investigate bacterial nanomachineries.
•Researching the fascinating ways our bodies deal with the bacteria present in our intestines has already yielded valuable insight, in which hormones (regulating gastrointestinal activity, systemic metabolism, and food intake) are generated in our gut.

JRA3: Translational proteomics
Improved analysis of clinical and patient-derived proteomes.

Progress:
•The Plasma Proteome Profiling pipeline, increases robustness and decreases the overall time of workflow to less than 3 hours from start to finalized mass spectrometer acquisition.
•First version protocol to enrich intracellular proteins that are present in body fluids following cytolysis of disease-affected cells and tissues.
•Investigation of specific types of protein abundance in varying types of cancers such as colorectal, lung cancer, and breast cancer patients.
•First version protocol to enrich intracellular proteins that are present in body fluids following cytolysis of disease-affected cells and tissues.

JRA4: Proteome organization: structural and spatial proteomics

Progress:
•Development of novel crosslinking reagent (Phox).
•Improvement of existing MS-based tools to characterize protein conformation and dynamics referred to as HDX-MS (hydrogen/deuterium exchange in solution with MS detection of the progress of exchange reactions).
•Improved application of limited proteolysis-coupled mass spectrometry (LiP-MS).
•Optimization and development of new and improved imaging technology methods for the visualization of proteins in their native cellular environment.
•Fast photochemical oxidation of proteins (FPOP) has resulted in the development of an analytical pipeline enabling top-down analysis of FPOP samples.
•Integration of subcellular fractionation with methods like LiP-MS and biotin painting and integration of proteomics- and antibody-based methods.
•Computational integration of image localization data with PPI data.
•Integration of highly multiplexed imaging with CODEX.
•Imaging-based investigation of the spatial reorganization of human host proteins upon SARS-CoV-2 infection.

Transnational Access provision

Over 173 access projects have been submitted to EPIC-XS, 110 have been accepted and 29 are, at the moment of writing this report, under review. All submitted projects go through an independent peer review process, by outside experts, which aim to prioritize based on feasibility and scientific excellence. Given that we are still in the beginning of this four-year project, we consider the number of applications a great success. The transnational access sites within EPIC-XS also provide hands-on training for researchers. This helps them to develop best practice workflows, and aid the dissemination of proteomics data into publicly available databases, thereby broadening the expertise of experienced scientists and those new to the field of proteomics. Also, standard operating procedures and new protocols are rapidly exchanged in between the access sites, to broaden and strengthen the services that can be offered.
We have seen from the start of EPIC-XS that there is a need for the provision of a European Proteomics infrastructure such as this one. The submission of over 170 user projects for trans-national access is a testament to this. We have identified and analyzed opportunities and problems related to access provision and have improved efforts in transparency to assist user expectations and access sites on data analysis and follow-up experiments. Extensive discussions were and will continue to be held with the management committee. These issues include trans-national access, networking, dissemination activities, and any other concerns the consortium may have. EPIC-XS also values the advice and input from its Scientific Advisory Board, its User, Review, and Industrial panels.