What Is Wrong with Clinical Proteomics?

Proteomics is defined as the large-scale study of proteins, particularly their structures and functions. Clinical proteomics aims to apply proteomic discoveries and technologies to patient care. One of the workhorses of proteomics is mass spectrometry (MS).9 Over the last few years we have witnessed spectacular advances in MS-based proteomics; these advances now allow almost complete proteome identification of complex biological fluids, tissues, cells, etc. in a matter of hours. Recently, mass spectrometers have become faster and more sensitive, and they can generate tremendous amounts of information related to protein primary structure, posttranslational modifications, splice variants, mutants, etc. Higher sensitivity for detecting individual proteins in complex mixtures in still an issue with proteomics. New instruments are continually upgraded and new methods for sample preparation are emerging, allowing faster and more sensitive measurements of many analytes in complex biological mixtures. Such methods may require analyte enrichment steps by using antibodies or other binding reagents. With all these advances, it was expected that MS-based proteomics could revolutionize medical sciences by providing insights into protein structure and function, but also, in translating some of these discoveries to the clinic. Particularly, it has been anticipated that novel disease biomarkers for diagnosis, monitoring, and prediction of therapy will be discovered and implemented into the clinic. The multiparametric nature of MS-based proteomics allows profiling of various biological fluids for clinical applications. Despite a 15-year effort, no major disease biomarkers have been discovered by using MS-based proteomics. Funding does not seem to be the problem since government bodies (including granting agencies such as the NIH) and diagnostics companies have already invested hundreds of millions of dollars toward this goal. In this Q&A we discuss with 4 experts in the field why this is the case and what the future may be for clinical proteomics. Why do you …