27,025 research outputs found
Stability from Structure: Metabolic Networks Are Unlike Other Biological Networks
In recent work, attempts have been made to link the structure of biochemical networks to their complex dynamics. It was shown that structurally stable network motifs are enriched in such networks. In this work, we investigate to what extent these findings apply to metabolic networks. To this end, we extend a previously proposed method by changing the null model for determining motif enrichment, by using interaction types directly obtained from structural interaction matrices, by generating a distribution of partial derivatives of reaction rates and by simulating enzymatic regulation on metabolic networks. Our findings suggest that the conclusions drawn in previous work cannot be extended to metabolic networks, that is, structurally stable network motifs are not enriched in metabolic networks
Network motif frequency vectors reveal evolving metabolic network organisation
At the systems level many organisms of interest may be described by their patterns of interaction, and as such, are perhaps best characterised via network or graph models. Metabolic networks, in particular, are fundamental to the proper functioning of many important biological processes, and thus, have been widely studied over the past decade or so. Such investigations have revealed a number of shared topological features, such as a short characteristic path-length, large clustering coefficient and hierarchical modular structure. However, the extent to which evolutionary and functional properties of metabolism manifest via this under- lying network architecture remains unclear. In this paper, we employ a novel graph embedding technique, based upon low-order network motifs, to compare metabolic network structure for 383 bacterial species categorised according to a number of biological features. In particular, we introduce a new global significance score which enables us to quantify important evolutionary relationships that exist between organisms and their physical environments. Using this new approach, we demonstrate a number of significant correlations between environmental factors, such as growth conditions and habitat variability, and network motif structure, providing evidence that organism adaptability leads to increased complexities in the resultant metabolic network
Feedbacks from the metabolic network to the genetic network reveal regulatory modules in E. coli and B. subtilis
The genetic regulatory network (GRN) plays a key role in controlling the
response of the cell to changes in the environment. Although the structure of
GRNs has been the subject of many studies, their large scale structure in the
light of feedbacks from the metabolic network (MN) has received relatively
little attention. Here we study the causal structure of the GRNs, namely the
chain of influence of one component on the other, taking into account feedback
from the MN. First we consider the GRNs of E. coli and B. subtilis without
feedback from MN and illustrate their causal structure. Next we augment the
GRNs with feedback from their respective MNs by including (a) links from genes
coding for enzymes to metabolites produced or consumed in reactions catalyzed
by those enzymes and (b) links from metabolites to genes coding for
transcription factors whose transcriptional activity the metabolites alter by
binding to them. We find that the inclusion of feedback from MN into GRN
significantly affects its causal structure, in particular the number of levels
and relative positions of nodes in the hierarchy, and the number and size of
the strongly connected components (SCCs). We then study the functional
significance of the SCCs. For this we identify condition specific feedbacks
from the MN into the GRN by retaining only those enzymes that are essential for
growth in specific environmental conditions simulated via the technique of flux
balance analysis (FBA). We find that the SCCs of the GRN augmented by these
feedbacks can be ascribed specific functional roles in the organism. Our
algorithmic approach thus reveals relatively autonomous subsystems with
specific functionality, or regulatory modules in the organism. This automated
approach could be useful in identifying biologically relevant modules in other
organisms for which network data is available, but whose biology is less well
studied.Comment: 15 figure
Low Degree Metabolites Explain Essential Reactions and Enhance Modularity in Biological Networks
Recently there has been a lot of interest in identifying modules at the level
of genetic and metabolic networks of organisms, as well as in identifying
single genes and reactions that are essential for the organism. A goal of
computational and systems biology is to go beyond identification towards an
explanation of specific modules and essential genes and reactions in terms of
specific structural or evolutionary constraints. In the metabolic networks of
E. coli, S. cerevisiae and S. aureus, we identified metabolites with a low
degree of connectivity, particularly those that are produced and/or consumed in
just a single reaction. Using FBA we also determined reactions essential for
growth in these metabolic networks. We find that most reactions identified as
essential in these networks turn out to be those involving the production or
consumption of low degree metabolites. Applying graph theoretic methods to
these metabolic networks, we identified connected clusters of these low degree
metabolites. The genes involved in several operons in E. coli are correctly
predicted as those of enzymes catalyzing the reactions of these clusters. We
independently identified clusters of reactions whose fluxes are perfectly
correlated. We find that the composition of the latter `functional clusters' is
also largely explained in terms of clusters of low degree metabolites in each
of these organisms. Our findings mean that most metabolic reactions that are
essential can be tagged by one or more low degree metabolites. Those reactions
are essential because they are the only ways of producing or consuming their
respective tagged metabolites. Furthermore, reactions whose fluxes are strongly
correlated can be thought of as `glued together' by these low degree
metabolites.Comment: 12 pages main text with 2 figures and 2 tables. 16 pages of
Supplementary material. Revised version has title changed and contains study
of 3 organisms instead of 1 earlie
Complex networks theory for analyzing metabolic networks
One of the main tasks of post-genomic informatics is to systematically
investigate all molecules and their interactions within a living cell so as to
understand how these molecules and the interactions between them relate to the
function of the organism, while networks are appropriate abstract description
of all kinds of interactions. In the past few years, great achievement has been
made in developing theory of complex networks for revealing the organizing
principles that govern the formation and evolution of various complex
biological, technological and social networks. This paper reviews the
accomplishments in constructing genome-based metabolic networks and describes
how the theory of complex networks is applied to analyze metabolic networks.Comment: 13 pages, 2 figure
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