PECA, proteome integral solubility alteration for chemical safety, a tool for target identification, and exposome impact analysis within the One Health framework

The EU's zero pollution ambition for 2050 is to reduce pollution to levels no longer harmful to human and environmental health. Current research has predominantly focused on human health, leaving a significant gap in understanding how these exposures affect animal health. This knowledge gap has consequences, as animal health is intricately linked to human health through the One Health concept. The lack of high-throughput methods to analyse the effects of the exposome on animal health not only endangers animal welfare but could pose risks to food safety and, consequently, human health.

As we present here, the Proteome Integral Solubility Alteration for Chemical Safety (PECA) implements the PISA assay for a fast and sensitive chemical safety assessment within the One Health concept. The modification aims: i) constrain the proteome of analysis on the globular native proteome; ii) increase the completeness of the target analysis by combining different principles that induce alteration in protein stability: temperature, acid or salt concentration; iii) select a temperature, acid, salt concentration that increases target identification while reducing sample requirement, iv) introduce lessons learnt from single-cell proteomics to reduce steps, time, and sample loss in sample preparation.

Here, we showed that PECA, as a simplified PISA assay, can identify proteins interacting with environmental chemicals, providing insights into the mechanism of action and predicting potential adverse effects. We first applied the method to determine protein targets of chemicals from human cell lines from the liver, skin, and endothelium, which are relevant to predicting the impact. Finally, we confirmed the method's applicability by analysing farm animal tissues. PECA aligns with the One Health concept by examining the broad impact of chemicals across different organisms, which is crucial for safeguarding the health of all species and ensuring the integrity of our food supply.

Funding: This work has been performed with funding from Cristobal Lab from the ERA-NET Marine Biotechnology project CYANOBESITY, which FORMAS, Sweden grant nr, cofounds. 2016-02004. The project GOLIATH has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 825489; IKERBASQUE, Basque Foundation for Science; Basque Government Research Grant IT-476-22 and LiU verification grant.