Serum Peptidome: Diagnostic Window into Pathogenic Processes following Occupational Exposure to Carbon Nanomaterials
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ABSTRACT: Growing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals, with significant augmentation of bioactive circulating peptides, the serum peptidome. While epidemiology among CNT/F workers reports few acute symptoms, there remains concern that CNT/F may prime for chronic disease. Here, the serum peptidome is assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Using a stratified design between High (>0.5 ug/m3) and Low (<0.1 ug/m3) CNT/F exposures, 2,726 serum peptides significantly distinguish the groups. Of these, 41 are found to be highly discriminatory after model building and exhibit a strong linear correlation with personal CNT/F exposures. The top-five peptide model offers ideal prediction with high accuracy (Q2=0.99916). Unsupervised validation affirms 43.5% of the serum peptidomic variance is attributable to CNT/F exposure. Peptide sequence identification reveals a predominant association with vascular pathology. ARHGAP21, ADAM15 and PLPP3 peptides suggest heightened cardiovasculature permeability and F13A1, FBN1 and VWDE peptides infer a pro-thrombotic state among High CNT/F workers. The serum peptidome affords a diagnostic window into pre-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring health risks.
INSTRUMENT(S): SYNAPT G2-Si
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: Andrew K Ottens
PROVIDER: MSV000087305 | MassIVE | Mon Apr 26 11:55:00 BST 2021
SECONDARY ACCESSION(S): PXD025646
REPOSITORIES: MassIVE
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