225 research outputs found
Hierarchical organization of modularity in metabolic networks
Spatially or chemically isolated functional modules composed of several
cellular components and carrying discrete functions are considered fundamental
building blocks of cellular organization, but their presence in highly
integrated biochemical networks lacks quantitative support. Here we show that
the metabolic networks of 43 distinct organisms are organized into many small,
highly connected topologic modules that combine in a hierarchical manner into
larger, less cohesive units, their number and degree of clustering following a
power law. Within Escherichia coli the uncovered hierarchical modularity
closely overlaps with known metabolic functions. The identified network
architecture may be generic to system-level cellular organization
Two-Peak and Three-Peak Optimal Complex Networks
A central issue in complex networks is tolerance to random failures and
intentional attacks. Current literature emphasizes the dichotomy between
networks with a power-law node connectivity distribution, which are robust to
random failures but fragile to targeted attacks, versus networks with an
exponentially decaying connectivity distribution, which are less tolerant to
failures but more resilient to attacks. We prove analytically that the optimal
network configuration under a classic measure of robustness is altogether
different from both of the above: in all cases, failure and/or attack, there
are no more than three distinct node connectivities in the optimal network
Matching experiments across species using expression values and textual information
Motivation: With the vast increase in the number of gene expression datasets deposited in public databases, novel techniques are required to analyze and mine this wealth of data. Similar to the way BLAST enables cross-species comparison of sequence data, tools that enable cross-species expression comparison will allow us to better utilize these datasets: cross-species expression comparison enables us to address questions in evolution and development, and further allows the identification of disease-related genes and pathways that play similar roles in humans and model organisms. Unlike sequence, which is static, expression data changes over time and under different conditions. Thus, a prerequisite for performing cross-species analysis is the ability to match experiments across species
Carbon catabolite repression correlates with the maintenance of near invariant molecular crowding in proliferating E. coli cells
Background: Carbon catabolite repression (CCR) is critical for optimal bacterial growth, and in bacterial (and yeast) cells it leads to their selective consumption of a single substrate from a complex environment. However, the root cause(s) for the development of this regulatory mechanism is unknown. Previously, a flux balance model (FBAwMC) of Escherichia coli metabolism that takes into account the crowded intracellular milieu of the bacterial cell correctly predicted selective glucose uptake in a medium containing five different carbon sources, suggesting that CCR may be an adaptive mechanism that ensures optimal bacterial metabolic network activity for growth.Results: Here, we show that slowly growing E. coli cells do not display CCR in a mixed substrate culture and gradual activation of CCR correlates with an increasing rate of E. coli cell growth and proliferation. In contrast, CCR mutant cells do not achieve fast growth in mixed substrate culture, and display differences in their cell volume and density compared to wild-type cells. Analyses of transcriptome data from wt E. coli cells indicate the expected regulation of substrate uptake and metabolic pathway utilization upon growth rate change. We also find that forced transient increase of intracellular crowding or transient perturbation of CCR delay cell growth, the latter leading to associated cell density-and volume alterations.Conclusions: CCR is activated at an increased bacterial cell growth rate when it is required for optimal cell growth while intracellular macromolecular density is maintained within a narrow physiological range. In addition to CCR, there are likely to be other regulatory mechanisms of cell metabolism that have evolved to ensure optimal cell growth in the context of the fundamental biophysical constraint imposed by intracellular molecular crowding. © 2013 Zhou et al.; licensee BioMed Central Ltd
Global organization of metabolic fluxes in the bacterium, Escherichia coli
Cellular metabolism, the integrated interconversion of thousands of metabolic
substrates through enzyme-catalyzed biochemical reactions, is the most
investigated complex intercellular web of molecular interactions. While the
topological organization of individual reactions into metabolic networks is
increasingly well understood, the principles governing their global functional
utilization under different growth conditions pose many open questions. We
implement a flux balance analysis of the E. coli MG1655 metabolism, finding
that the network utilization is highly uneven: while most metabolic reactions
have small fluxes, the metabolism's activity is dominated by several reactions
with very high fluxes. E. coli responds to changes in growth conditions by
reorganizing the rates of selected fluxes predominantly within this high flux
backbone. The identified behavior likely represents a universal feature of
metabolic activity in all cells, with potential implications to metabolic
engineering.Comment: 15 pages 4 figure
The topological relationship between the large-scale attributes and local interaction patterns of complex networks
Recent evidence indicates that the abundance of recurring elementary
interaction patterns in complex networks, often called subgraphs or motifs,
carry significant information about their function and overall organization.
Yet, the underlying reasons for the variable quantity of different subgraph
types, their propensity to form clusters, and their relationship with the
networks' global organization remain poorly understood. Here we show that a
network's large-scale topological organization and its local subgraph structure
mutually define and predict each other, as confirmed by direct measurements in
five well studied cellular networks. We also demonstrate the inherent existence
of two distinct classes of subgraphs, and show that, in contrast to the
low-density type II subgraphs, the highly abundant type I subgraphs cannot
exist in isolation but must naturally aggregate into subgraph clusters. The
identified topological framework may have important implications for our
understanding of the origin and function of subgraphs in all complex networks.Comment: pape
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