Improved mass spectrometry aids proteomics

Proteomics, the identification and quantification of proteins by direct measurement of constituent peptides, is filling a void created by a slowdown in the availability of biomarkers available for disease detection and monitoring.

Mass spectrometry is the key technology in using proteomics to stage disease, identify drug targets, and understand the mechanism of action of leading drug candidates better, said Steven A. Carr, PhD, a senior scientific leader in protein biochemistry and proteomics at the Broad Institute of Harvard University, Boston, and the Massachusetts Institute of Technology, Cambridge, MA.

Approaches to identification of biomarkers include pattern- and identify-based methods. In the identify approach, sequences are produced from peptides, separated, and analyzed against a genomic database to determine their identify, which may or may not be correct, Dr. Carr said during a proteomics session at the annual meeting of the Association for Research in Vision and Ophthalmology.

"The process of discovery leads to candidates, not biomarkers, so you need to do something else to take your candidates through to verification or qualification," Dr. Carr said. The search can be refined with various strategies, including a new, larger set of patient samples, immunodepletion, and the use of new, hybrid MS devices that have higher resolution and better accuracy.

Results can also be improved by starting the analysis with proximal fluids rather than blood, with the patient acting as his or her own control, if possible.

"Potential biomarkers are enriched in proximal fluids," Dr. Carr noted.

Candidate verification has been largely ignored in the biomarker identification process until recently, but is, in fact, a critical intermediate step, he added.