106,314 research outputs found
Rigidity and flexibility of biological networks
The network approach became a widely used tool to understand the behaviour of
complex systems in the last decade. We start from a short description of
structural rigidity theory. A detailed account on the combinatorial rigidity
analysis of protein structures, as well as local flexibility measures of
proteins and their applications in explaining allostery and thermostability is
given. We also briefly discuss the network aspects of cytoskeletal tensegrity.
Finally, we show the importance of the balance between functional flexibility
and rigidity in protein-protein interaction, metabolic, gene regulatory and
neuronal networks. Our summary raises the possibility that the concepts of
flexibility and rigidity can be generalized to all networks.Comment: 21 pages, 4 figures, 1 tabl
Edge vulnerability in neural and metabolic networks
Biological networks, such as cellular metabolic pathways or networks of
corticocortical connections in the brain, are intricately organized, yet
remarkably robust toward structural damage. Whereas many studies have
investigated specific aspects of robustness, such as molecular mechanisms of
repair, this article focuses more generally on how local structural features in
networks may give rise to their global stability. In many networks the failure
of single connections may be more likely than the extinction of entire nodes,
yet no analysis of edge importance (edge vulnerability) has been provided so
far for biological networks. We tested several measures for identifying
vulnerable edges and compared their prediction performance in biological and
artificial networks. Among the tested measures, edge frequency in all shortest
paths of a network yielded a particularly high correlation with vulnerability,
and identified inter-cluster connections in biological but not in random and
scale-free benchmark networks. We discuss different local and global network
patterns and the edge vulnerability resulting from them.Comment: 8 pages, 4 figures, to appear in Biological Cybernetic
Assessing the significance of knockout cascades in metabolic networks
Complex networks have been shown to be robust against random structural
perturbations, but vulnerable against targeted attacks. Robustness analysis
usually simulates the removal of individual or sets of nodes, followed by the
assessment of the inflicted damage. For complex metabolic networks, it has been
suggested that evolutionary pressure may favor robustness against reaction
removal. However, the removal of a reaction and its impact on the network may
as well be interpreted as selective regulation of pathway activities,
suggesting a tradeoff between the efficiency of regulation and vulnerability.
Here, we employ a cascading failure algorithm to simulate the removal of single
and pairs of reactions from the metabolic networks of two organisms, and
estimate the significance of the results using two different null models:
degree preserving and mass-balanced randomization. Our analysis suggests that
evolutionary pressure promotes larger cascades of non-viable reactions, and
thus favors the ability of efficient metabolic regulation at the expense of
robustness
Formulating genome-scale kinetic models in the post-genome era.
The biological community is now awash in high-throughput data sets and is grappling with the challenge of integrating disparate data sets. Such integration has taken the form of statistical analysis of large data sets, or through the bottom-up reconstruction of reaction networks. While progress has been made with statistical and structural methods, large-scale systems have remained refractory to dynamic model building by traditional approaches. The availability of annotated genomes enabled the reconstruction of genome-scale networks, and now the availability of high-throughput metabolomic and fluxomic data along with thermodynamic information opens the possibility to build genome-scale kinetic models. We describe here a framework for building and analyzing such models. The mathematical analysis challenges are reflected in four foundational properties, (i) the decomposition of the Jacobian matrix into chemical, kinetic and thermodynamic information, (ii) the structural similarity between the stoichiometric matrix and the transpose of the gradient matrix, (iii) the duality transformations enabling either fluxes or concentrations to serve as the independent variables and (iv) the timescale hierarchy in biological networks. Recognition and appreciation of these properties highlight notable and challenging new in silico analysis issues
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
ModuLand plug-in for Cytoscape: determination of hierarchical layers of overlapping network modules and community centrality
Summary: The ModuLand plug-in provides Cytoscape users an algorithm for
determining extensively overlapping network modules. Moreover, it identifies
several hierarchical layers of modules, where meta-nodes of the higher
hierarchical layer represent modules of the lower layer. The tool assigns
module cores, which predict the function of the whole module, and determines
key nodes bridging two or multiple modules. The plug-in has a detailed
JAVA-based graphical interface with various colouring options. The ModuLand
tool can run on Windows, Linux, or Mac OS. We demonstrate its use on protein
structure and metabolic networks. Availability: The plug-in and its user guide
can be downloaded freely from: http://www.linkgroup.hu/modules.php. Contact:
[email protected] Supplementary information: Supplementary
information is available at Bioinformatics online.Comment: 39 pages, 1 figure and a Supplement with 9 figures and 10 table
Analysis of the impact degree distribution in metabolic networks using branching process approximation
Theoretical frameworks to estimate the tolerance of metabolic networks to
various failures are important to evaluate the robustness of biological complex
systems in systems biology. In this paper, we focus on a measure for robustness
in metabolic networks, namely, the impact degree, and propose an approximation
method to predict the probability distribution of impact degrees from metabolic
network structures using the theory of branching process. We demonstrate the
relevance of this method by testing it on real-world metabolic networks.
Although the approximation method possesses a few limitations, it may be a
powerful tool for evaluating metabolic robustness.Comment: 17 pages, 4 figures, 4 table
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