The Proteomic Revolution Has Changed the Capabilities of Analytical


The Proteomic Revolution Has Changed the Capabilities of Analytical...

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The Proteomic Revolution Has Changed the Capabilities of Analytical Chemistry

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he term “proteomics” was first used in print in 1995,1 coinciding with the beginning of the exponential growth of this new postgenomic area of research. Rapid global expansion was based on the realization2⫺4 that automated comparison of MS measurements of peptides to protein sequences available in databases could provide rapid and automated identification of proteins in laboratory samples. The greatly expanded market produced by the growth of MS-based proteomic studies has led to novel and significantly improved MS instrumentation with increased sensitivity; expanded functions; robust integration of HPLC; and, most importantly, highly automated computer control to facilitate the analysis of the very complex samples generated in many of these workflows. In particular, many new types of tandem and hybrid instruments have been commercialized to provide low- and high-resolution MS/MS spectra and multiple reaction monitoring measurements. These improvements also benefit investigators who work with small molecules and other kinds of biopolymers and provide the foundation for further developments in ion chemistry and ion activation research. Because the simultaneous examination of many proteins generates complex mixtures of peptides, a second area, separation science, has also been highly stimulated. Two-dimensional gel electrophoresis (the precedent proteomic technique) has seen an expanded market and significantly improved technology, including the commercial availability of robust and standardized gradient gels; the development of fluorescent dye tags that allow direct quantitative comparison of multiple samples on one gel; longer immobilized pH gradient (IPG) strips; narrow-range IPG strips; and the development of computer programs to digitize, align, and quantify protein patterns on gel arrays. Interest in gel-free proteomics has catalyzed development of novel, multistage HPLC separation procedures for peptides and proteins, and commercially available variations of new solution and capillary isoelectric focusing devices. Capillary

and nanoflow HPLC, in particular, have become more robust. The recent introduction of commercial LC instrumentation that operates in the ultrahigh-pressure regime and the development of new column stationary phases have increased the power of LC to separate complex proteomic (and other) mixtures. The third leg of the proteomics stool is, of course, bioinformatics. Many bioinformatics challenges in proteomics, such as the recognition and calculation of isotope clusters and charge-state assignment, are traditional MS problems that have found new applications in proteomics, but data volume, high-throughput workflows, and the rich variety of bioinformatics data resources have required significant innovation. Promising work is under way on the development of label-free approaches for semiquantitative comparisons of samples in LC/MS-based workflows. The organization of proteins, once identified, into functional classes and pathways provides a foundation for systems biology, unifying the insights of genomics, transcriptomics, and proteomics in one framework. We can ask how the proteomic revolution and its rapidly expanding analytical capabilities have changed biological research. Here, the focus for many investigators has moved to proteins as the active agents of genes. Because many proteins are viewed simultaneously, discovery experiments are possible. At the same time, more effort can be expended to address protein function and protein networks, because less effort is required to address protein sequences. Temporal and spatial pan-cellular dynamics are under examination as proteomics opens new doors in cell biology as well as in the search for clinical biomarkers. Analytical chemistry has provided the foundation and the catalysis for this important new area of science. Three cheers for the MS designers, the separation scientists, the bioinformatics community, and the agencies that see fit to fund their developments and inventions.

(1) Wasinger, V. C.; et al. Electrophoresis 1995, 16, 1090–1094. (2) Henzel, W. J.; et al. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 5011–5015. (3) Eng, J. K.; McCormack, A. L.; Yates, J. R. J. Am. Soc. Mass Spectrom. 1994, 5, 976–989. (4) Shevchenko, A.; et al. Anal. Chem. 1996, 68, 850–858.

10.1021/AC802043C  2008 AMERICAN CHEMICAL SOCIETY

Published on Web 10/31/2008

NOVEMBER 1, 2008 / ANALYTICAL CHEMISTRY

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