Beyond the genome to the proteome

Abstract

The sequence of the human genome has been decoded and a post-genome era is now beginning. This is the start of the protein/peptide era. Working in the fundamental research division of a pharmaceutical company and being engaged in studies on the research and development of new drugs based upon genomic information, it was clear to me that genomic information was useful, significant and indispensable in driving forward to new drug discovery. However, it is also true that we need more than that. I have faced multiple barriers in pursuing genomic information alone. There are numerous dead-end stories in genome-based new drug discovery and in many cases, those hurdles are very hard to get over. What approach can be a breakthrough of this bottleneck? I believe that one answer is research into proteins. The proteome describes all the proteins within an organism. The proteome analysis research field promises a bright future for the discovery of new drugs, diagnosis and therapeutics. I believe the mass spectrometer(MS) will be a key instrument in this research. The contribution of mass spectrometry was recently recognized in the Nobel Prize for Chemistry 2002, for 'the discovery of Soft Laser Desorption/Ionization' awarded to Mr. Koichi Tanaka. There is no doubt that the MS will play an essential role in accelerating proteome analysis. However, the present proteome analysis technology has not yet reached a sufficient scientific level. Further improvements of both hardware and software are necessary. For the hardware, improvements in sensitivity, accuracy and high-throughput, in addition to equipment for ultra-micro analysis applied to the analysis of the proteome should be addressed. Regarding software, we need to develop new chemistries for proteome analyses and propose original, user-friendly proteome analysis methods. In this review, starting with a briefing on genome-based drug discovery, I will discuss a new concept for proteome analysis based on mass spectrometry and new methodologies. This 'next generation' platform may provide a solution for the development of an integrated system that will contribute to our understanding of clinical information/bioinformatics, therapeutics, diagnosis and even drug discovery.