A uniform data processing pipeline enables harmonized nanoparticle protein corona analysis across proteomics core facilities

Corona (planetary geology) Biomolecule
DOI: 10.1038/s41467-023-44678-x Publication Date: 2024-01-06T14:01:43Z
ABSTRACT
Abstract Protein corona, a layer of biomolecules primarily comprising proteins, forms dynamically on nanoparticles in biological fluids and is crucial for predicting nanomedicine safety efficacy. The protein composition the corona typically analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Our recent study, involving identical samples by 17 proteomics facilities, highlighted significant data variability, with only 1.8% proteins consistently identified across these centers. Here, we implement an aggregated database search unifying parameters such as variable modifications, enzyme specificity, number allowed missed cleavages stringent 1% false discovery rate at peptide levels. Such uniform dramatically harmonizes data, increasing reproducibility percentage consistency-identified unique distinct cores. Specifically, out 717 quantified 253 (35.3%) are shared among top 5 facilities (and 16.2% 11 facilities). Furthermore, note that reduction alkylation important steps sample processing expected, omitting reduces total peptides around 20%. These findings underscore need standardized procedures analysis, which vital advancing clinical applications nanoscale biotechnologies.
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