Special Issue of Clinical Chemistry on Proteomics
Contributed by Glen L. Hortin, PhD, MD, FACB
The February 2010 issue of Clinical Chemistry was devoted to diagnostic application of proteomics. There was also an associated podcast "Proteomics Special Issue" that can be accessed at http://media.aacc.org/CCJPodcasts/010410ProteomicsSpecial.mp3. N. Leigh Anderson, Steven A. Carr, and myself assisted as guest co-editors of this issue, and one of the initial challenges was addressing the questions: what is proteomics? And, what should be included in the special issue? The term "proteomics" has come to have varying meanings to different individuals and increasingly defies clear definition. In practice, we decided not to try to define "proteomics," and to consider submissions that represented examples of "recent developments in the diagnostic applications of protein analysis." In fact, the introduction to the Proteomics Special Issue does not even use the term "proteomics" a single time (Clin Chem 2010;56(2):149-151. The introduction also points out that, although most of the attention is directed at the identification of new diagnostic markers, there are many other sources of innovation-- application of new analytical technologies, platform engineering, reagent development, interpretation of results, preanalytical processes, standardization and quality assurance of assays-- that often have as much or more impact on the clinical laboratory.
The February issue provides a sampling of diverse areas of investigation and recent progress in protein and peptide analysis. Over the past few years, the analysis of peptides and small proteins in plasma by matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometry has been a controversial approach for cancer diagnosis. Rigorous analysis of this approach has not been able to verify it as a useful diagnostic approach for diagnosis of several cancers such as ovarian and prostate cancer. There are many other areas, however, where great progress is being achieved. Many approaches are being developed for the simultaneous quantitative analysis of multiple components. Multiplex immunoassay is a technique coming into increased use in the clinical laboratory. Analysis of tryptic peptides by liquid chromatography tandem mass spectrometry with stable isotope internal standards appears to be means of accurately quantifying multiple components without depending on the availability of antibodies specific for a particular protein. This approach may impact clinical laboratory practice by serving as a reference method to standardize assays. Use of mass spectrometry also serves to identify the structural variation of peptides and proteins. One report describes the diversity of molecular forms of parathyroid hormone. Applications of tandem mass spectrometry are likely to have a significant clinical impact and role in analysis of peptides as this technique recently has shown for analysis of steroid hormones.
The Proteomics issue provides unique contributions that address the problems of validating and obtaining regulatory approval for new laboratory tests. Mock test submissions to the US Food and Drug Administation are presented that serve as examples of the types of issues that need to be addressed.
This is an exciting time as new technologies and new disease markers progress towards potential clinical application. The February issue provides an overview of many new developments but it was not possible to provide a comprehensive survey within 180 pages. A few examples of other areas of progress not covered in this issue are major advances in allergen testing with expanded arrays of recombinant or purified antigens, new markers for kidney injury, and identification of microorganisms by MALDI TOF mass spectrometry.