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A Peptide-Centric DIA-NN Reanalysis Uncovers Structurally Coherent Salivary Signatures of Type 2 Diabetes

Year: 2026

Type: article

Abstract: Type 2 diabetes (T2D) causes systemic metabolic and inflammatory changes that affect the oral cavity, but salivary molecular markers remain poorly characterized. A peptide-centric reanalysis of salivary proteomics data was performed using DIA-NN for peptide-level quantification, without collapsing peptide signals into protein-level summaries. Although the qualitative peptide repertoire was largely conserved between T2D and control samples (>96% overlap), T2D showed coordinated quantitative changes in specific peptide subsets. Differentially abundant peptides primarily originated from complement C3, alpha-2-macroglobulin, serotransferrin, mucins, apolipoproteins, and hemoglobin, with a significant enrichment of oxidized cysteine-containing peptides, indicating redox imbalance and low-grade inflammation. Structural analysis with AlphaFold showed that T2D-associated peptides are located in solvent-exposed and conformationally dynamic regions of proteins. These findings suggest that disease specificity in diabetic saliva occurs mainly at the peptide level, offering mechanistic insight into non-invasive biomarker identification and longitudinal disease monitoring.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27042040

Author: Rui Miguel Pinheiro Vitorino

Institutions: Universidade do Porto, University of Aveiro

Language: English

Topic: Advanced Proteomics Techniques and Applications

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499