Global plasma proteome quantification using internal standard triggered targeted analyses
The ability of plasma proteomics studies to deliver useful protein biomarkers has remained lower than initial expectations, prompting a redefinition of the plasma biomarker development pipeline. One proposed measure consisted in the implementation of a “rectangular” approach, relying exclusively on broad proteome profiling (through DDA or DIA analyses) across large cohorts for both the discovery and validation/verification stages. We describe here an alternative global quantification workflow, relying on a high density targeted acquisition method implemented on next generation Orbitrap mass spectrometers. This adaptation of the internal standard triggered PRM method leverages spiked-in stable isotopically labeled (SIL) peptides to drive the systematic screening of more than 500 plasma proteins per analysis across large sample sets.
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