The advent of large-scale DNA sequencing has transformed biological research in a short span of time. With the advancement in the discovery of most human genes, the next necessity is to explore the key molecules (proteins) responsible for biological problems so as to achieve an in-depth knowledge of complex biological processes. In this article, the crucial contribution of proteomics to our understanding of biology and medicine, through the global analysis of gene products, is discussed.
The term "proteomics or proteome" refers to the total protein complement expressed by the genome, and generally means the high-throughput systematic separation, identification and characterization of proteins (the term "proteomics" was first coined in 1995). Proteomics attempts to analyze all the proteins in a cell from the point of view of their individual functions and understand how the interaction of specific proteins with other cellular components (e.g., nucleic acids, membranes, organelles, etc.) affects the function of those proteins. There is a wide difference in the understanding of two terms 'genomics and proteomics' in the respect that the genome is well defined and static in all the cells of an organism while the proteome is dynamic in nature and continually changes in response to external and internal conditions. For example, E.coli expresses different proteins and, thus has a different proteome depending on the type of media it grows. Similarly, during multicellular mammalian development, specialized cells express different proteins, but with characteristic proteomes, representing diverse tissues.
A major tool for proteomics is in silico-biology, making comprehensive use of the data derived from the genome-sequencing efforts. However, the information which can be deduced from the genome data about their encoded proteins is rather limited. For example, transcript expression profiles usually do not reflect the actual protein expression profiles. Combining PCR and proteome analysis showed that the correlation between changes in mRNA levels and altered protein abundance was only 0.48. There is a strong demand for genome-wide elaboration of protein expression profiles. The limitation of proteomics is the lack of genome-wide experimental approaches for the analysis of protein expression, post-translational modifications, 3-D structure, enzymatic activity, etc. A protein database in which all available information is integrated, is being constructed for many prokaryotes and some model eukaryotes, including Arabidopsis.
A broad definition of proteomics involves many different areas of study. These include protein-protein interaction studies, protein modifications, protein function, and protein localization studies, to name a few. The ultimate aim of proteomics approach is not only limited to the identification of all the proteins in a cell but also to create a complete 3-D map of the cell proteome to indicate the location of proteins. The fulfillments of these goals certainly require contributions from many disciplines, such as molecular biology, biochemistry and bioinformatics. The large-scale nucleotide sequencing of genomic DNA and expressed sequence tags has made a paramount growth of proteomics. Protein identification (by MS or Edman sequencing) relies on the presence of some form of database for the given organism. The majority of DNA and protein sequence information has been accumulated over the last 5-10 years. The genome sequencing of a promising number of microorganisms has been completed and that of remaining is underway. At present, the sequencing of 5 eukaryotic genomes have been completed: Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and Drosophila melanogaster. In addition, the rice, mouse and human genomes are near completion.
Potentiality of Proteomics
Researchers have now realized that the mere accumulation of vast and complete sequence of genomes is not only sufficient to gain an in-depth insight into the biological function. A cell in its normal function is dependent upon a large number of regulatory, metabolic and biochemical pathways for its survival. Researchers have found a complementary relationship between proteomics and genomics because of its emphasis on the gene products, which are believed to be the active agents in the cells. It should be also agreed upon that the presence of an open reading frame does not necessarily entail the gene as functional. Thus, proteomics directly contributes to drug development, as almost all drugs are directed against proteins. Any modifications of the proteins that are not apparent from the DNA sequence, such as isoforms and post-transcriptional and post-translational levels, make proteomics distinct and a valuable tool.
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