Figure 1. Dynamic range of the human plasma proteome and current detection methods.

Dynamic ranges for classical plasma proteins (high-medium abundance) and selected clinically relevant proteins. Intervals refer to published 95% reference ranges, or quartiles or ranges where reference intervals were unavailable. Lower ends of reference intervals have not been established for a few proteins (arrowhead). Affinity-based methods essentially capture proteins across the entire abundance spectrum but may be offset by specificity, whereas mass spectrometry (MS) has excellent specificity but is limited to proteins with high and medium abundance. Newer MS methods such as multiple reaction monitoring (MRM), immuno-MRM (iMRM) and isobaric tags (iTRAQ) may detect lower-abundance proteins and with additional separation steps reach as low as affinity methods. Ultrasensitive single molecule detection (SMD) assays are necessary to detect proteins at very low abundance, down to fg/ml. 2DE, 2-dimensional gel electrophoresis. LC-MS, liquid chromatography MS.