PEG Precipitation Followed by Albumin Depletion for Plasma Proteomics Analysis

The mass spectrometry (MS)-based blood plasma or serum proteomic analysis is limited by interference from albumin, immunoglobins, and other highly abundant proteins. We have found that poly­(ethylene glycol) (PEG) can efficiently precipitate some of these proteins except albumin. By PEG precipitation followed by albumin depletion, additional proteins and N-glycoproteins can be identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the plasma. In-depth LC-MS/MS proteomic analyses of the whole plasma, its 10% and 20% PEG-precipitated pellets, and albumin-depleted supernatants have profiled 2943, 2242, 3162, 2187, and 2028 proteins respectively, yielding 5040 proteins in total and thus expanding the plasma proteome coverage. Therefore, PEG precipitation and albumin depletion should be used as a general plasma processing method for successful proteomic discoveries of blood biomarkers.