Introduction of proteomics
...to homogeneity of species by following a select biological activity through extensive steps of fractionation. This involved a detailed structural, functional and regulatory analysis of each isolated component and was followed by attempts to reconstitute the biological process from isolated components. Traditional biochemistry was conducted in what was basically a hypothesis-driven manner where questions for study were asked in series, such as which single protein causes a given biological activity or effect. In this environment individual laboratories championed individual proteins or biochemical pathways with great success and began to piece together information on cellular function, for the most part, one protein at a time. The technology for conducting massively parallel experiments was simply not available for them to move beyond this approach, but more importantly the lack of protein and DNA sequence databases limited the manner in which questions could be asked with any available technology. Now, however, with the availability of complete sequence databases that allow in principle the amino acid sequence of every protein theoretically predicted to be encoded by a species to be calculated, it is possible to ask questions of multiple proteins in parallel without first proposing a specific hypothesis (Ideker et al. 2001). This is not to say that hypothesis-driven research is missing from current global experiments as practiced in proteomics (Aebersold et al. 2000; Harry et al. 2000; Pandey and Mann 2000), but that hypotheses for testing may be generated in a less biased manner by allowing the data from global experiments to suggest new hypotheses for testing. The proteome (Wasinger et al. 1995; Loo et al. 1996; Wilkins et al. 1996; Hochstrasser 1998), when defined as the protein complement expressed by a genome, is somewhat restrictive and implies a static nature. This definition is in fact a good starting point but in reality the proteome is much more dynamic than the definition implies. The types of expressed proteins, their abundance, state of modification, subcellular location, etc. are dependent on the physiological state of the cell or tissue. Therefore, the proteome reflects the cellular state or the external conditions encountered by a cell and proteome analysis can be viewed ...