Operational Taxon-Function Framework in MetaX: Unveiling Taxonomic and Functional Associations in Metaproteomics

Metaproteomics analyzes the functional dynamics of microbial communities by identifying peptides and mapping them to the most likely proteins and taxa. One challenge in this field lies in seamlessly integrating taxonomic and functional annotations to accurately represent the contributions of individual microbial taxa to functional diversity. We introduce MetaX, a comprehensive tool for analyzing taxon-function relationships in metaproteomics by mapping peptides to their lowest common ancestors and assigning functions based on proportional thresholds, ensuring accurate peptide-level mappings. Importantly, MetaX introduces the Operational Taxon-Function (OTF), a new conceptual unit for exploring microbial roles and interactions within ecosystems. Additionally, MetaX includes extensive statistical and visualization tools, establishing it as a robust platform for metaproteomics analysis. We validated MetaX by reanalyzing ex vivo gut microbiome metaproteomic data exposed to various sweeteners, yielding more detailed results than traditional protein analysis. Furthermore, using the peptide-centric approach and OTF, we observed that <i>Parabacteroides distasonis</i> significantly responds to certain sweeteners, highlighting its role in modifying specific metabolic functions. With its intuitive, user-friendly interface, MetaX facilitates a detailed study of the complex interactions between microbial taxa and their functions in metaproteomics. It enhances our understanding of microbial roles in ecosystems and health.