By Dr Tomislav Meštrović, MD, PhD
The term proteome, coined in 1995, refers to the protein composition of the genome, while the term proteomics represents a systematic analysis of those proteins. Proteomics is used to detect protein expression patterns at a given time in response to a specific stimulus, but also to determine functional protein networks that exist at the level of the cell, tissue, or whole organism.
In the presence of bountiful genomic sequence data available today, the field of proteomics has grown into the leading arena for the identification and characterization of cellular gene products (i.e. proteins) that are present, absent, or altered under a certain environmental, physiological and pathophysiological conditions.
Proteomics in medicine
Proteomics is vital for decrypting how proteins interact as a system and for comprehending the functions of cellular systems in human disease. Nevertheless, due the fact that the proteome is several orders of magnitude more complex than the genome and highly fluid in nature, large-scale proteomic analysis remains challenging.
Cancer biologists have made the first attempts to utilize proteomics for diagnostic and prognostic purposes. A serum-based proteomic pattern diagnostics has soon been developed, which represents a new method of diagnosis and disease identification for ovarian cancer detection.
The concept behind this is that the diagnostic endpoint for ovarian cancer detection is not a single analyte, but a proteomic pattern composed of many individual proteins. Furthermore, defining signaling pathways in ovarian cancer cells through proteomic analysis gives us the opportunity to optimize the use of molecularly targeted agents against central and biologically active pathways.
Protein-sequence data are now available for many microorganisms, providing us with tools for understanding their resistance to antimicrobial drugs and for identifying novel agents for treating drug-resistant disease. Surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) is now employed to rapidly diagnose invasive aspergillosis, tuberculosis, sleeping sickness and Chagas' disease.
Advances in mass spectrometry, coupled with better isolation and enrichment techniques which allows the separation of organelles and membrane proteins, made the in-depth analysis of cardiac proteome a reality. Evolution of proteomic techniques has allowed more detailed investigation of molecular mechanisms underlying cardiovascular disease, facilitating the identification of not only modified proteins, but also the nature of their modification.
Proteomics is also becoming a part of the quality-control process in transfusion medicine with an aim to verify the identity, safety, potency and purity of various blood products. The proteomic approach is a valuable way to implement a global screening of storage-related lesions of red blood cells and to study the mechanisms of possible biological consequences on the transfusion recipient.
Proteomics in drug development
Since disease processes and treatments are often manifesting at the protein level, proteomics has received much attention as a drug development platform. The pattern of protein changes after drug application gives important information about the mechanism of action, either for therapeutic or toxicological effects.
A majority of large pharmaceutical companies now have a proteomics-oriented biotechnological (or academic) partner or have started their own proteomics division. Usual applications of this field in the drug industry include target identification and validation, identification of biomarker efficacy and toxicity from easily attainable biological fluids, as well as investigations into mechanisms of drug action or toxicity.
Proteome mining is today used to discover new antimalarial drugs that target purine binding proteins in the blood stage of infection. It represents a functional proteomics approach used to assess protein information from the analysis of specific subproteomes. This approach exploits the serendipitous nature of drug discovery, simply because it expands the hit rate over a conventional screen by a factorial of the proteome that is bound.
Many of the top-selling drugs today either act by targeting proteins or are proteins themselves. Advances in proteomics may help researchers to eventually create medications that are “personalized” for different individuals in order to achieve better effectiveness and fewer side effects.
Last Updated: May 5, 2015