New paradigms suggest that many aspects of cellular function are controlled by rapid, stochastic, combinatorial processes. The implications of these new paradigms for proteomics are considered in relation to the information content of top-down and bottom-up proteomics approaches. Functional evidence and Current Proteomics experiments suggest that phenotypic variation of individual proteins is a major form of control for the combinatorial processes and that in many cases top-down proteomics approaches will be essential for proteomics investigations of cellular function. It is suggested that the new paradigms and the nature of the general cellular processes that affect protein phenotypes should be taken into account in the development of proteomics methodology. More generally, the coupling of stochastic, combinatorial processes to energy-dependent processes that change protein phenotypes may represent one of the basic principles of cellular function.
Keywords: proteomics, mass spectrometry, hypoxia, nuclear receptors, endothelin, phosphorylation
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