Understanding the roadmap of metabolism by pathway analysis.
ABSTRACT The theoretical investigation of the structure of metabolic systems has recently attracted increasing interest. In this chapter, the basic concepts of metabolic pathway analysis are described and various applications are outlined. In particular, the concepts of nullspace and elementary flux modes are explained. The presentation is illustrated by a simple example from tyrosine metabolism and a system describing lysine production in Corynebacterium glutamicum. The latter system gives rise to 37 elementary modes, 36 of which produce lysine with different molar yields. The examples illustrate that metabolic pathway analysis is a useful tool for better understanding the complex architecture of intracellular metabolism, for determining the pathways on which the molar conversion yield of a substrate-product pair under study is maximal, and for assigning functions to orphan genes (functional genomics). Moreover, problems emerging in the modeling of large networks are discussed. An outlook on current trends in the field concludes the chapter.
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ABSTRACT: ABSTRACT: The search and validation of novel disease biomarkers requires the complementary power of professional study planning and execution, modern profiling technologies and related bioinformatics tools for data analysis and interpretation. Biomarkers have considerable impact on the care of patients and are urgently needed for advancing diagnostics, prognostics and treatment of disease. This survey article highlights emerging bioinformatics methods for biomarker discovery in clinical metabolomics, focusing on the problem of data preprocessing and consolidation, the data-driven search, verification, prioritization and biological interpretation of putative metabolic candidate biomarkers in disease. In particular, data mining tools suitable for the application to omic data gathered from most frequently-used type of experimental designs, such as case-control or longitudinal biomarker cohort studies, are reviewed and case examples of selected discovery steps are delineated in more detail. This review demonstrates that clinical bioinformatics has evolved into an essential element of biomarker discovery, translating new innovations and successes in profiling technologies and bioinformatics to clinical application.Journal of clinical bioinformatics. 01/2011; 1(1):2.
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ABSTRACT: A homoserine auxotroph strain of Corynebacterium glutamicum accumulates storage compound trehalose with lysine when limited by growth. Industrially lysine is produced from C. glutamicum through aspartate biosynthetic pathway, where enzymatic activity of aspartate kinase is allosterically controlled by the concerted feedback inhibition of threonine plus lysine. Ample threonine in the medium supports growth and inhibits lysine production (phenotype-I) and its complete absence leads to inhibition of growth in addition to accumulating lysine and trehalose (phenotype-II). In this work, we demonstrate that as threonine concentration becomes limiting, metabolic state of the cell shifts from maximizing growth (phenotype-I) to maximizing trehalose phenotype (phenotype-II) in a highly sensitive manner (with a Hill coefficient of 4). Trehalose formation was linked to lysine production through stoichiometry of the network. The study demonstrated that the net flux of the population was a linear combination of the two optimal phenotypic states, requiring only two experimental measurements to evaluate the flux distribution. The property of linear combination of two extreme phenotypes was robust for various medium conditions including varying batch time, initial glucose concentrations and medium osmolality.Systems and Synthetic Biology 06/2013; 7(1-2).
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ABSTRACT: The liver is a fascinating organ and performs a wide range of functions necessary for life. Because the hepatocyte is the major functional cell type found in the liver, it is important that we better understand its role in health and disease. Functional hepatocytes have been derived from many sources, including human stem cell populations. These models offer new opportunities to further our understanding of human liver biology from diverse genotypes and, in the future, to facilitate the development of novel medicines or cell-based therapies. This review discusses limitations in current cell-based models and the advantages offered by pluripotent stem cell-derived hepatocytes.Annual Review of Pharmacology 01/2013; 53:147-59. · 21.54 Impact Factor