Abstract
Analysis of the human genome has increased our knowledge of the genes that are associated with disease. At the same time, however, it has become clear that having complete DNA sequences alone is not sufficient to elucidate the biological functions of the proteins that they encode. For this reason, proteomics—the analysis of proteins—has become increasingly attractive, because the proteome reflects both the intrinsic genetic programming of a cell and the impact of its immediate environment. The principal goals of clinical proteomics are to identify biomarkers for the early diagnosis of disease and potential targets for therapeutic intervention. Other goals include the identification of biomarkers for the early detection of disease recurrence (relapse) and how they might be combined with diagnostic imaging techniques to improve the sensitivity for detecting disease. This Review describes conventional proteomic technologies, their strengths and limitations, and demonstrates their application to clinical practice, with specific reference to their use in the gastroenterology field.
Key Points
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Proteomics has become increasingly attractive, because the proteome reflects the intrinsic genetic program of the cell and the impact of its immediate environment
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The principal goals of clinical proteomics are to identify biomarkers for the early diagnosis of disease and potential targets for therapeutic intervention; other goals include the identification of biomarkers for the early detection of disease recurrence and their combination with diagnostic imaging techniques to improve the sensitivity for detecting disease
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The development of automated, high-throughput proteomic technologies has enabled large numbers of clinical samples to be analyzed simultaneously, which is a prerequisite for the application of proteomics to clinical practice
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Conventional proteomics techniques include protein separation (e.g. two-dimensional gel electrophoresis, differential in-gel electrophoresis), protein identification (mass spectrometry) and protein functional analysis (e.g. X-ray crystallography, protein arrays)
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Limitations concerning reliability, reproducibility and minimization of pre-analysis variables need to be addressed before large-scale proteomics can be applied in routine clinical practice
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Large-scale prospective studies are needed to validate and prove the utility of the biomarkers identified using proteomic technology
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Acknowledgements
S Din is funded by a Cancer Research UK Clinical Fellowship. Research within the Gastrointestinal Unit is supported by the Wellcome Trust, CORE, the National Association for Crohn's and Colitis, the Medical Research Council, Action Medical Research and the Scottish Executive. None of the funding agencies had any input into the production of this manuscript.
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Din, S., Lennon, A., Arnott, I. et al. Technology Insight: the application of proteomics in gastrointestinal disease. Nat Rev Gastroenterol Hepatol 4, 372–385 (2007). https://doi.org/10.1038/ncpgasthep0872
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DOI: https://doi.org/10.1038/ncpgasthep0872
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