Article
Understanding the roadmap of metabolism by pathway analysis.
Department of Bioinformatics, Friedrich-Schiller University of Jena, Germany.
Methods in molecular biology (Clifton, N.J.)
02/2007;
358:199-226.
DOI:10.1007/978-1-59745-244-1_12
pp.199-226
Source: PubMed
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Citations (0)
- Cited In (3)
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Article: The smallest chemical reaction system with bistability.
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ABSTRACT: Bistability underlies basic biological phenomena, such as cell division, differentiation, cancer onset, and apoptosis. So far biologists identified two necessary conditions for bistability: positive feedback and ultrasensitivity. Biological systems are based upon elementary mono- and bimolecular chemical reactions. In order to definitely clarify all necessary conditions for bistability we here present the corresponding minimal system. According to our definition, it contains the minimal number of (i) reactants, (ii) reactions, and (iii) terms in the corresponding ordinary differential equations (decreasing importance from i-iii). The minimal bistable system contains two reactants and four irreversible reactions (three bimolecular, one monomolecular).We discuss the roles of the reactions with respect to the necessary conditions for bistability: two reactions comprise the positive feedback loop, a third reaction filters out small stimuli thus enabling a stable 'off' state, and the fourth reaction prevents explosions. We argue that prevention of explosion is a third general necessary condition for bistability, which is so far lacking discussion in the literature.Moreover, in addition to proving that in two-component systems three steady states are necessary for bistability (five for tristability, etc.), we also present a simple general method to design such systems: one just needs one production and three different degradation mechanisms (one production, five degradations for tristability, etc.). This helps modelling multistable systems and it is important for corresponding synthetic biology projects. The presented minimal bistable system finally clarifies the often discussed question for the necessary conditions for bistability. The three necessary conditions are: positive feedback, a mechanism to filter out small stimuli and a mechanism to prevent explosions. This is important for modelling bistability with simple systems and for synthetically designing new bistable systems. Our simple model system is also well suited for corresponding teaching purposes.BMC Systems Biology 10/2009; 3:90. · 3.15 Impact Factor -
Article: Exploring the Dynamics of Large-Scale Biochemical Networks: A Computational Perspective
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ABSTRACT: The complexity of even comparatively simple biochemical systems necessitates a computational description to explore and eventually understand the dynamics emerging from the underlying networks of cellular interactions. Within this contribution, several aspects relating to a computational description of large-scale biochemical networks are discussed. Topics range from a brief description of the rationales for computational modeling to the utilization of Monte Carlo methods to explore dynamic properties of biochemical networks. The main focus is to outline a path towards the construction of large-scale kinetic models of metabolic networks in the face of incomplete and uncertain knowledge of kinetic parameters. It is argued that a combination of phenotypic data, large-scale measurements, heuristic assumptions about generic rate equations, together with appropriate numerical schemes, allows for a fast and efficient way to explore the dynamic properties of biochemical networks. In this respect, several recently proposed strategies that are based on Monte Carlo methods are an important step towards large-scale kinetic models of cellular metabolism.The Open Bioinformatics Journal 01/2011; 511:4-15. -
Article: Bioinformatics in aging research: a workshop report.
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ABSTRACT: Evidence is accumulating that the first genuine antiaging interventions (e.g., approved pharmaceutical, nutriceutical, and stem-cell-based therapies) will become available within the next decades. Model organism data, next-generation sequencing, and further advances call for sophisticated large-scale data analysis. To present the state-of-the art and to talk about upcoming tasks and challenges in the bioinformatics and systems biology of aging-related data, a workshop on Bioinformatics in Ageing Research convened leading experts from Europe on May 4-5, 2010, in Rostock/Warnemünde. This meeting report summarizes talks and gives some outlook into future developments.Rejuvenation Research 12/2010; 13(6):763-7. · 3.83 Impact Factor
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Keywords
37 elementary modes
assigning functions
complex architecture
different molar yields
elementary flux modes
functional genomics
intracellular metabolism
lysine production
metabolic pathway analysis
molar conversion yield
nullspace
orphan genes
pathways
problems
produce lysine
simple example
substrate-product pair
theoretical investigation
tyrosine metabolism
useful tool