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A wonderful and amusing piece extolling the virtues of a top-down and quantitative approach to understanding complex biological networks. The radio engineer succeeds because s/he has a wiring diagram, not merely a list of isolated components that may be present but without any knowledge of their values and what they interact with.
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Lazebnik Y. Can a biologist fix a radio? - or, what I learned while studying apoptosis. Cancer Cell. 2:2002;179-182 A wonderful and amusing piece extolling the virtues of a top-down and quantitative approach to understanding complex biological networks. The radio engineer succeeds because s/he has a wiring diagram, not merely a list of isolated components that may be present but without any knowledge of their values and what they interact with.
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Genetic programming methods can provide a straightforward link between the genotype and for example metabolomic phenotype of an organism, which maybe useful in both genetic and other nonlinear mappings. The strategy could clearly be used to determine important connectivities in nonlinear metabolic networks.
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Kell D.B. Genotype:phenotype mapping: genes as computer programs. Trends Genet. 18:2002;555-559 Genetic programming methods can provide a straightforward link between the genotype and for example metabolomic phenotype of an organism, which maybe useful in both genetic and other nonlinear mappings. The strategy could clearly be used to determine important connectivities in nonlinear metabolic networks.
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The authors implemented an entirely closed loop system of automated experimentation in which a computer containing background knowledge proposed the 'best' (most discriminating) experiment, performed it and evaluated it seriatim before performing the next cycle, without human intervention. The method was applied to the identification of mutants in aromatic amino acid biosynthesis in baker's yeast, using growth and nutrient feeding experiments. The strategy could be applied to many areas of post-genomic biology and elsewhere.
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King R.D., Whelan K.E., Jones F.M., Reiser P.G.K., Bryant C.H., Muggleton S.H., Kell D.B., Oliver S.G. Functional genomic hypothesis generation and experimentation by a robot scientist. Nature. 427:2004;247-252 The authors implemented an entirely closed loop system of automated experimentation in which a computer containing background knowledge proposed the 'best' (most discriminating) experiment, performed it and evaluated it seriatim before performing the next cycle, without human intervention. The method was applied to the identification of mutants in aromatic amino acid biosynthesis in baker's yeast, using growth and nutrient feeding experiments. The strategy could be applied to many areas of post-genomic biology and elsewhere.
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Metabolome data differ from transcriptome and proteome data and have special bioinformatics needs, which are reviewed here. Special emphasis is placed on the important issue of data visualisation.
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Mendes P. Emerging bioinformatics for the metabolome. Brief Bioinform. 3:2002;134-145 Metabolome data differ from transcriptome and proteome data and have special bioinformatics needs, which are reviewed here. Special emphasis is placed on the important issue of data visualisation.
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A first-class and easy-to-read review of the technology and science of metabolomics, concentrating on plants, and including a helpful discussion of database issues.
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Sumner L.W., Mendes P., Dixon R.A. Plant metabolomics: large-scale phytochemistry in the functional genomics era. Phytochemistry. 62:2003;817-836 A first-class and easy-to-read review of the technology and science of metabolomics, concentrating on plants, and including a helpful discussion of database issues.
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Fiehn O. Metabolomics: the link between genotypes and phenotypes. Plant Mol Biol. 48:2002;155-171 A very nice review, including a detailed discussion of the differences between metabolomics, metabolic profiling and metabolic fingerprinting and methods for performing them. GC-MS remains the most common and 'gold standard' method, but other methods are being introduced.
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A review of metabonomics (metabolomics) with specific reference to its use in assessing mechanisms of toxicity from the metabolic profiles in urine. A particularly useful feature of this review is the helpful figure relating specific markers in the profiles to the major target sites.
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Nicholson J.K., Connelly J., Lindon J.C., Holmes E. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov. 1:2002;153-161 A review of metabonomics (metabolomics) with specific reference to its use in assessing mechanisms of toxicity from the metabolic profiles in urine. A particularly useful feature of this review is the helpful figure relating specific markers in the profiles to the major target sites.
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A review that aims to concentrate on methods aimed at exploiting metabolomic measurements for deciphering metabolic networks, but also covering many of the existing or emerging methods for measuring the metabolome itself.
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Fiehn O., Weckwerth W. Deciphering metabolic networks. Eur J Biochem. 270:2003;579-588 A review that aims to concentrate on methods aimed at exploiting metabolomic measurements for deciphering metabolic networks, but also covering many of the existing or emerging methods for measuring the metabolome itself.
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A review of the 'metabonomics' agenda, concentrating on high-resolution NMR and pattern recognition, although somewhat misrepresenting the origins and usage of the term 'metabolomics'. Stress is laid on the use of automation in making such methods rapid and robust, which means the cost-per-sample can be low even when using rather expensive equipment.
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Lindon J.C., Holmes E., Nicholson J.K. So what's the deal with metabonomics? Metabonomics measures the fingerprint of biochemical perturbations caused by disease, drugs, and toxins. Anal Chem. 75:2003;384A-391A A review of the 'metabonomics' agenda, concentrating on high-resolution NMR and pattern recognition, although somewhat misrepresenting the origins and usage of the term 'metabolomics'. Stress is laid on the use of automation in making such methods rapid and robust, which means the cost-per-sample can be low even when using rather expensive equipment.
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A review that stresses the relationship between diet, the gut microflora, and the host's genome, metabolome and disease. It includes a figure illustrating 'metabolic space' with over 5000 samples and provides a clear statement of the authors' distinction between the metabolome and the 'metabonome', the latter of which is said to relate to the metabolic responses to pathophysiological stimuli or genetic modification.
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Nicholson J.K., Wilson I.D. Understanding 'global' systems biology: Metabonomics and the continuum of metabolism. Nat Rev Drug Discov. 2:2003;668-676 A review that stresses the relationship between diet, the gut microflora, and the host's genome, metabolome and disease. It includes a figure illustrating 'metabolic space' with over 5000 samples and provides a clear statement of the authors' distinction between the metabolome and the 'metabonome', the latter of which is said to relate to the metabolic responses to pathophysiological stimuli or genetic modification.
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One way to improve separations, and hence improve the effective dynamic range, is to use multidimensional methods in which a first dimension effects a partial separation and imperfectly separated peaks are then resolved in a second dimension. This review gives a very useful overview of existing methods and trends.
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