2023BBSRC-NSF/BIO: Making Single-Cell Proteomics data FAIR

High-throughput mass spectrometry (MS)-based proteomics approaches have become an essential tool in biological research. Single-cell proteomics (SCP) approaches, which can provide unprecedented insights into the protein repertoire, have greatly developed in recent years thanks to key developments in MS instrumentation, automation in sample processing, new data acquisition approaches, and improved data analysis tools. Whereas the more established single cell transcriptomics (sc-RNAseq) approaches assume that the mRNA levels are reliable surrogates for protein levels, SCP approaches represent the only approach to directly quantify proteomes at a single-cell level. SCP, is therefore, at a stage at which developments are needed to enable researchers to better comply with open science practises and, as a key part, with the FAIR (Findable, Accessible, Interoperable, Reusable) data principles, which have become common in proteomics and in the life sciences as a whole. In 2023, the SCP community developed the first guidelines for performing, benchmarking and reporting SCP experiments. We will follow some of the recommendations included in the guidelines such as: (i) facilitating compliance with reporting standards, with a special focus in sample metadata and the experimental design; and (ii) the need to develop further existing open resources to support SCP datasets. In this ‘SCP-FAIR’ proposal, we will then make SCP proteomics data more FAIR, following the recommendations of the community. The main objectives are: (i) Formalise open data and metadata standards and related open software for SCP approaches; (ii) Extend current open data analysis and quality control pipelines for SCP datasets; (iii) Reuse public SCP datasets by performing reproducible data reanalyses; (iv) Integrate the results of the reanalyses into the PRIDE database (via the ‘PRIDE SCP’ data portal), and in expression atlases: the Single Cell Expression Atlas (EMBL-EBI) and the CellxGene portal (Chan Zuckerberg Initiative); (v) Perform and enable downstream (meta)analysis of the results of the reanalyses aiming at different biological interpretations, e.g. interpreting protein covariation across single cells; and (vi) carry out training and outreach activities to disseminate appropriately the outputs of the proposal. This work will benefit more directly scientists working in proteomics and/or in single-cell biology. However, all life scientists generally will be able to benefit from the improved FAIR data practices, including the availability of more FAIR SCP data in additional data resources such as the ones outlined above. To summarise, ‘SCP-FAIR’ is focused on developing open data standards, bioinformatics infrastructure, and generating new knowledge from public datasets in the rapidly developing field of SCP. It is therefore perfectly aligned with the “Biological informatics” theme, prioritised in the 2023-24 BBSRC/NSF call. The two groups involved: the EMBL-EBI Proteomics team and the Slavov laboratory are world-leaders in their respective domains. As such we expect that the synergies gained from this collaboration will have a huge impact in the field.