The clinical plasma proteome: a survey of clinical assays for proteins in plasma and serum.

An analysis of all US Food and Drug Administration (FDA) approvals for protein-based assays through 2008 reveals 109 unique protein targets in plasma or serum, as well as 62 additional tests for peptides, protein posttranslational modifications, protein complexes, autoantibodies against endogenous proteins, and blood cell proteins. A further 96 unique protein targets are assayed in plasma by laboratory-developed tests available for clinical use in the US, yielding a total of 205 proteins that include products of approximately 211 genes (excluding immunoglobulins). These tests provide quantitative measurements for approximately 1% of the human protein gene products, defining a practical clinical plasma proteome. The rate of introduction of new protein analytes has remained essentially flat over the past 15 years, averaging 1.5 new proteins per year (median of 1 per year). This rate falls far short of that needed to support projected medical needs and indicates serious deficiencies in the protein biomarker pipeline, from which no proteomics-discovered analytes have yet emerged.