Peptide abundance correlations in metaproteomics enhance taxonomic and functional analysis of the human gut microbiome.

Mass spectrometry (MS)-based proteomics is widely used for quantitative protein profiling and protein interaction studies. However, most current research focuses on single-species proteomics, while protein interactions within complex microbiomes, composed of hundreds of bacterial species, remain largely unexplored. In this study, we analyzed peptide abundance correlations within a metaproteomics dataset derived from in vitro cultured human gut microbiomes subjected to various drug treatments. Our analysis revealed that peptides from the same protein or taxon exhibited correlated abundance changes. By using t-SNE for visualization, we generated a peptide correlation map in which peptides from the same taxon formed distinct clusters. Furthermore, peptide abundance correlations enabled genome-level taxonomic assignments for a greater number of peptides. For instance, 1880 (48.9%) of the 3845 peptides initially assigned only to the family Bacteroidaceae could now be assigned to a specific genome. In species representative genome subsets, peptide correlation networks based on taxon-normalized peptide abundance (TNPA) linked functionally related peptides and provided insights into uncharacterized proteins. Altogether, our study demonstrates that analyzing peptide abundance correlations enhances both taxonomic and functional analyses in human gut metaproteomics research.