Abstract
Liquid chromatography-tandem mass spectrometry was used to analyze plasma proteins of volunteers (control) and patients with glioblastoma multiform (GBM). A database search was pre-set with a variable post-translational modification (PTM): phosphorylation, acetylation or ubiquitination. There were no significant differences between the control and the GBM groups regarding the number of protein identifications, sequence coverage or number of PTMs. However, in GBM plasma, we unambiguously observed a decreased fraction in post-translationally modified peptides identified with high quality. The disease-specific PTM patterns were extracted and mapped to the set of FDA-approved plasma protein markers. Decreases of 46% and 24% in the number of acetylated and ubiquitinated peptides, respectively, were observed in the GBM samples. Significance of capturing disease-associated patterns of protein modifications was envisaged.
Highlights
Post-translational modifications (PTMs) of proteins affect pathways linked to cell signaling/ transduction, trafficking, storing, expression, binding and/or affinity and cause serious health consequences including cancer
Analysis of glioblastoma multiform (GBM) plasma proteome upon PTM-sensitive search
The examination of the plasma proteome was performed by Progenesis LC-mass spectrometry (MS) software (Nonlinear Dynamics Ltd.), with which two peak lists were generated and exported for MS/MS search
Summary
Post-translational modifications (PTMs) of proteins affect pathways linked to cell signaling/ transduction, trafficking, storing, expression, binding and/or affinity and cause serious health consequences including cancer. Most PTMs alter the molecular mass of a protein, mass spectrometry (MS) is the ideal analytical tool for PTM profiling of proteomes [2]. PTMs can rigorously compromise protein identification results if proper accounting of combinatorial variants is not performed. Database search engines support options to identify peptides with specific modifications, search algorithms cannot comprehensively identify PTMs in a single pass because of high false discovery rates (FDRs) [3, 4]. The validation of the protein match to the mass-spectra usually relies on number of identified peptides, semi-probabilistic scores and sequence coverage. In liquid chromatography-tandem MS (LC-MS/MS) experiments the sequence coverage roughly correlates with protein abundance.
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