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  • 1
    Language: English
    In: Analytical chemistry, 16 October 2012, Vol.84(20), pp.8442-7
    Description: The combination of high-resolution LC-MS-based untargeted metabolomics with stable isotope tracing provides a global overview of the cellular fate of precursor metabolites. This methodology enables detection of putative metabolites from biological samples and simultaneous quantification of the pattern and extent of isotope labeling. Labeling of Trypanosoma brucei cell cultures with 50% uniformly (13)C-labeled glucose demonstrated incorporation of glucose-derived carbon into 187 of 588 putatively identified metabolites in diverse pathways including carbohydrate, nucleotide, lipid, and amino acid metabolism. Labeling patterns confirmed the metabolic pathways responsible for the biosynthesis of many detected metabolites, and labeling was detected in unexpected metabolites, including two higher sugar phosphates annotated as octulose phosphate and nonulose phosphate. This untargeted approach to stable isotope tracing facilitates the biochemical analysis of known pathways and yields rapid identification of previously unexplored areas of metabolism.
    Keywords: Metabolic Networks and Pathways ; Metabolomics -- Methods ; Trypanosoma Brucei Brucei -- Metabolism
    ISSN: 00032700
    E-ISSN: 1520-6882
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  • 2
    Language: English
    In: FEBS Letters, 18 March 2013, Vol.587(6), pp.677-682
    Description: ► We provide the exact probability distribution of the rank product statistics. ► Exact -values offer an improvement over permutation and gamma calculation. ► This improvement is important in all areas of biological data analysis. The rank product method is a widely accepted technique for detecting differentially regulated genes in replicated microarray experiments. To approximate the sampling distribution of the rank product statistic, the original publication proposed a permutation approach, whereas recently an alternative approximation based on the continuous gamma distribution was suggested. However, both approximations are imperfect for estimating small tail probabilities. In this paper we relate the rank product statistic to number theory and provide a derivation of its exact probability distribution and the true tail probabilities.
    Keywords: Rank Product Method ; Microarray ; Permutational Inference ; Gamma Approximation ; Exact Inference ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0014-5793
    E-ISSN: 1873-3468
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  • 3
    In: Molecular Microbiology, March 2012, Vol.83(5), pp.884-893
    Description: Synthetic Biology is in a critical phase of its development: it has finally reached the point where it can move from proof‐of‐principle studies to real‐world applications. Secondary metabolite biosynthesis, especially the discovery and production of antibiotics, is a particularly relevant target area for such applications of synthetic biology. The first international conference to explore this subject was held in Spain in October 2011. In four sessions on General Synthetic Biology, Filamentous Fungal Systems, Systems, and Tools and Host Structures, scientists presented the most recent technological and scientific advances, and a final‐day Forward Look Plenary Discussion identified future trends in the field.
    Keywords: Antibiotics -- Conferences, Meetings And Seminars ; Metabolites -- Conferences, Meetings And Seminars;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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  • 4
    Language: English
    In: FEBS Letters, 21 July 2011, Vol.585(14), pp.2389-2394
    Description: ► We generated genome-scale metabolic models of 37 actinomycete species for comparative analysis. ► Using single-gene knockouts we inferred genomic maps of essential enzymes in each species. ► Combining all models, we were able to construct a global enzyme association network. ► We identified the conserved “core network” and the “essential core network” of the entire group. ► Low-degree enzymes (in linear pathways) are generally more essential than high-degree enzymes. Actinomycetes are highly important bacteria. On one hand, some of them cause severe human and plant diseases, on the other hand, many species are known for their ability to produce antibiotics. Here we report the results of a comparative analysis of genome-scale metabolic models of 37 species of actinomycetes. Based on knockouts we generated topological and genomic maps for each organism. Combining the collection of genome-wide models, we constructed a global enzyme association network to identify both a conserved “core network” and an “essential core network” of the entire group. As has been reported for low-degree metabolites in several organisms, low-degree enzymes (in linear pathways) turn out to be generally more essential than high-degree enzymes (in metabolic hubs).
    Keywords: Flux Balance Analysis ; Constraint-Based Metabolic Model ; Systems Biology ; Streptomyces ; Secondary Metabolite ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0014-5793
    E-ISSN: 1873-3468
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  • 5
    Language: English
    In: Current Opinion in Biotechnology, December 2015, Vol.35, pp.46-51
    Description: Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems.
    Keywords: Engineering
    ISSN: 0958-1669
    E-ISSN: 1879-0429
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  • 6
    Language: English
    In: Analytical chemistry, 15 November 2011, Vol.83(22), pp.8703-10
    Description: Metabolomics is an emerging field of postgenomic biology concerned with comprehensive analysis of small molecules in biological systems. However, difficulties associated with the identification of detected metabolites currently limit its application. Here we demonstrate that a retention time prediction model can improve metabolite identification on a hydrophilic interaction chromatography (HILIC)-high-resolution mass spectrometry metabolomics platform. A quantitative structure retention relationship (QSRR) model, incorporating six physicochemical variables in a multiple-linear regression based on 120 authentic standard metabolites, shows good predictive ability for retention times of a range of metabolites (cross-validated R(2) = 0.82 and mean squared error = 0.14). The predicted retention times improved metabolite identification by removing 40% of the false identifications that occurred with identification by accurate mass alone. The importance of this procedure was demonstrated by putative identification of 690 metabolites in extracts of the protozoan parasite Trypanosoma brucei, thus allowing identified metabolites to be mapped onto an organism-wide metabolic network, providing opportunities for future studies of cellular metabolism from a global systems biology perspective.
    Keywords: Trypanosoma Brucei Brucei -- Chemistry
    ISSN: 00032700
    E-ISSN: 1520-6882
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  • 7
    Language: English
    In: FEBS Letters, 2005, Vol.579(28), pp.6289-6294
    Description: Over the last decade, epidermal growth factor (EGF) signaling has been used repeatedly as a testbed for pioneering computational systems biology. Recent breakthroughs in our molecular understanding of EGF signaling pose new challenges for mathematical modeling strategies. Three key areas emerge as particularly relevant: the pervasive importance of compartmentalization and endosomal trafficking; the complexity of signalosome complexes; and the regulatory influence of diffusion and spatiality. Each one of them demands a drastic change in current computational approaches. We discuss recent developments in the field that address these emerging aspects in a new generation of more realistic – and potential more useful – models of EGF signaling.
    Keywords: Epidermal Growth Factor ; Computational Modeling ; Systems Biology ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0014-5793
    E-ISSN: 1873-3468
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  • 8
    Language: German
    In: Arachnologische Mitteilungen, 01 September 2017, Vol.54, pp.24-27
    Description: An analysis of public DNA barcoding data confirms that the extraction of Arboricaria Bosmans, 2000 from the genus Micaria Westring, 1851 would require the division of Micaria into at least five (and probably more) individual genera, to restore the monophyly of Micaria sensu stricto. Such an excessive splitting of a homogenous and well-defined genus would be neither desirable nor practical, and consequently Arboricaria should be considered a subjective junior synonym of Micaria, as suggested earlier (syn. conf.).
    Keywords: Araneae ; DNA Barcoding ; Cladistics ; Phylogenetic Systematics ; Paraphyly ; Spider ; Zoology
    ISSN: 1018-4171
    E-ISSN: 2199-7233
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  • 9
    Language: English
    In: BMC Research Notes, Sept 7, 2011, Vol.4, p.325
    Description: Background Streptomyces coelicolor, a model organism of antibiotic producing bacteria, has one of the largest genomes of the bacterial kingdom, including 7825 predicted protein coding genes. A large number of these genes, nearly 34%, are functionally orphan (hypothetical proteins with unknown function). However, in gene expression time course data, many of these functionally orphan genes show interesting expression patterns. Results In this paper, we analyzed all functionally orphan genes of Streptomyces coelicolor and identified a list of "high priority" orphans by combining gene expression analysis and additional phylogenetic information (i.e. the level of evolutionary conservation of each protein). Conclusions The prioritized orphan genes are promising candidates to be examined experimentally in the lab for further characterization of their function.
    Keywords: Gene Expression -- Research ; Genomes -- Physiological Aspects ; Genomes -- Research ; Streptomyces -- Physiological Aspects ; Streptomyces -- Research
    ISSN: 1756-0500
    Source: Cengage Learning, Inc.
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  • 10
    Language: English
    In: BMC Research Notes, Sept 7, 2011, Vol.4, p.325
    Description: Background Streptomyces coelicolor, a model organism of antibiotic producing bacteria, has one of the largest genomes of the bacterial kingdom, including 7825 predicted protein coding genes. A large number of these genes, nearly 34%, are functionally orphan (hypothetical proteins with unknown function). However, in gene expression time course data, many of these functionally orphan genes show interesting expression patterns. Results In this paper, we analyzed all functionally orphan genes of Streptomyces coelicolor and identified a list of "high priority" orphans by combining gene expression analysis and additional phylogenetic information (i.e. the level of evolutionary conservation of each protein). Conclusions The prioritized orphan genes are promising candidates to be examined experimentally in the lab for further characterization of their function.
    Keywords: Gene Expression -- Research ; Genomes -- Physiological Aspects ; Genomes -- Research ; Streptomyces -- Physiological Aspects ; Streptomyces -- Research
    ISSN: 1756-0500
    Source: Cengage Learning, Inc.
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