A One Health Framework for Proteomics Across the Tree of Life to Advance Food Security, Animal Health, and Ecosystem Resilience

As global ecosystems and food systems face unprecedented anthropogenic and climatic challenges, there is a demand for an integrated understanding of biological systems. Proteomics has emerged as a definitive approach offering a direct view of the molecular phenotype, yet it is traditionally separated into plant and animal disciplines. With recent advances in mass spectrometry (MS) and bioinformatics tools, this prospective review proposes that combining a One Health proteomics approach with deep-learning data analysis can revolutionize global food security, animal productivity, and ecosystem health by uncovering proteoform signatures that drive resilience across life. The potential of a unified One Health proteomic framework, highlighting major developments, including 4D proteomics, Data-Independent Acquisition (DIA), and single-cell resolution, and emphasizes their capacity to resolve the complex proteoform landscape across kingdoms. Review emphasizes the applications of proteogenomics as a cross-disciplinary tool to improve genome annotations, explain evolutionary differences, discover biomarkers in animals and resolve complex signaling networks in plants under stress. Nevertheless, contemporary proteogenomics methods still show limitations in their ability to comprehensively resolve proteoforms due to the fact that the use of peptide-based approaches makes it difficult to fully appreciate the post-translational modifications specific to each protein isoform. We show that One Health proteomics will provide a transformative roadmap for deciphering the functional proteoform signatures that underpin resilience across the tree of life.