Proteomics advances

As the exploration of the human proteome advances from better known proteins to more and more obscure ones, the significance of de novo sequencing as the primary source of information is hkely to grow. Similarly, the identification of spUce variants, mutations, and modifications calls for increasing number of de novo investigations. 

Tao WA, Aebersold R (2003) Advances in quantitative proteomics via stable isotope tagging and mass spectrometry. Curr Opin Biotechnol 14 110-118... 

By all accounts, the hypothesis of formation of DNA+adamantane+amino acid nanoarchitectures is currently immature and amenable to many technical modifications. Advancement in this subject requires a challenging combination of state-of-the-art approaches of organic chemistry, biochemistry, proteomics, and surface science. 

Although the feasibility of the proteomics or bioinformatics approach has been demonstrated, considerable room remains for improved methods for selective solublization of protein biomarkers and for rapid cleavage to produce peptides. There is also demand for advanced instrumentation to collect, process, and analyze microorganisms. 

Chalmers MJ et al. Advances in mass spectrometry for proteome analysis. Curr Opin Biotechnol 2000 11 384—390. 

Proteomics is a child of disparate parents the revolutionary advent of genomic sequencing and the evolutionary extension of mass spectrometry to permit the analysis of peptides. The fusion of these advances initially created a vision of full inventories of proteins in a biological unit, such as a cell, a subcellular fraction, or a physiological fluid. Good progress has been made toward this in some cases [11], but the focus is shifting from encyclopedic surveys toward an emphasis on quantitative... 

Methods based on liquid chromatography-mass spectrometry (LC-MS) and universally accepted search algorithms permit reliable identifications of low levels of proteins at high sensitivity [6]. Even semispecialized protein chemistry labs can readily identify proteins at the level of a few picomoles (10 pmol of a 50-kDa protein is 500 ng). Specialized groups with access to the latest advances in HPLC and mass spectrometry routinely work with subpicomolar quantities. Chemical proteomics as discussed here requires the more advanced equipment. 

When fresh or frozen tissue is used for proteomic analyses, the results cannot be related directly to the clinical course of diseases in a timely manner. Instead, researchers frequently reduce the number of interesting proteins to a manageable number and then attempt to use immunohistochemistry to understand the implications of proteomic changes in archival formalin-fixed, paraffin-embedded (FFPE) tissue for which the clinical course has been established.3 Unfortunately, immunohistochemistry is a semiquantitative pro-teomic method, and the choice of interesting proteins must occur without advance knowledge of the clinical course of the disease or the response to therapy. If routinely fixed and embedded archival tissues could be used for standard proteomic methods such as 2-D gel electrophoresis and mass spectrometry (MS), these powerful techniques could be used to both qualitatively and quantitatively analyze large numbers of tissues for which the clinical course has been established. However, analysis of archival FFPE tissues by... 

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