Counting the Proteins in Plasma

Featured Article: Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, et al. The human plasma proteome: a non-redundant list developed by combination of four separate sources. Mol Cell Proteomics 2004;3:311–26.2The problem of enumerating protein components in plasma has challenged the best analytical technologies for more than 80 years. The first generation of proteomics methodologies (particularly 2-dimensional electrophoresis) had detected about 60 plasma proteins by the early 1990s 1, and these proteins were more or less the same as those previously tabulated in Frank Putnam's reference books (The Plasma Proteins) and purified by the Behring Institute and others. Almost all are present at concentrations >1 μmol/L (roughly 50 mg/L). The development of sensitive specific immunoassays during this period, however, clearly demonstrated the presence of at least a few proteins at concentrations 1000- to 100 000-fold lower, raising the important question of how many proteins lay below the tip of the iceberg then visible to systematic proteome mapping.When systematic protein methods began to improve about a decade ago, with mass spectrometry and genomic data combining to enable efficient …