55,731 research outputs found
Reduction of dynamical biochemical reaction networks in computational biology
Biochemical networks are used in computational biology, to model the static
and dynamical details of systems involved in cell signaling, metabolism, and
regulation of gene expression. Parametric and structural uncertainty, as well
as combinatorial explosion are strong obstacles against analyzing the dynamics
of large models of this type. Multi-scaleness is another property of these
networks, that can be used to get past some of these obstacles. Networks with
many well separated time scales, can be reduced to simpler networks, in a way
that depends only on the orders of magnitude and not on the exact values of the
kinetic parameters. The main idea used for such robust simplifications of
networks is the concept of dominance among model elements, allowing
hierarchical organization of these elements according to their effects on the
network dynamics. This concept finds a natural formulation in tropical
geometry. We revisit, in the light of these new ideas, the main approaches to
model reduction of reaction networks, such as quasi-steady state and
quasi-equilibrium approximations, and provide practical recipes for model
reduction of linear and nonlinear networks. We also discuss the application of
model reduction to backward pruning machine learning techniques
Thermodynamically Consistent Coarse Graining of Biocatalysts beyond Michaelis--Menten
Starting from the detailed catalytic mechanism of a biocatalyst we provide a
coarse-graining procedure which, by construction, is thermodynamically
consistent. This procedure provides stoichiometries, reaction fluxes (rate
laws), and reaction forces (Gibbs energies of reaction) for the coarse-grained
level. It can treat active transporters and molecular machines, and thus
extends the applicability of ideas that originated in enzyme kinetics. Our
results lay the foundations for systematic studies of the thermodynamics of
large-scale biochemical reaction networks. Moreover, we identify the conditions
under which a relation between one-way fluxes and forces holds at the
coarse-grained level as it holds at the detailed level. In doing so, we clarify
the speculations and broad claims made in the literature about such a general
flux--force relation. As a further consequence we show that, in contrast to
common belief, the second law of thermodynamics does not require the currents
and the forces of biochemical reaction networks to be always aligned.Comment: 14 pages, 5 figure
Computer simulations of electrorheological fluids in the dipole-induced dipole model
We have employed the multiple image method to compute the interparticle force
for a polydisperse electrorheological (ER) fluid in which the suspended
particles can have various sizes and different permittivites. The point-dipole
(PD) approximation being routinely adopted in computer simulation of ER fluids
is shown to err considerably when the particles approach and finally touch due
to multipolar interactions. The PD approximation becomes even worse when the
dielectric contrast between the particles and the host medium is large. From
the results, we show that the dipole-induced-dipole (DID) model yields very
good agreements with the multiple image results for a wide range of dielectric
contrasts and polydispersity. As an illustration, we have employed the DID
model to simulate the athermal aggregation of particles in ER fluids both in
uniaxial and rotating fields. We find that the aggregation time is
significantly reduced. The DID model accounts for multipolar interaction
partially and is simple to use in computer simulation of ER fluids.Comment: 22 pages, 7 figures, submitted to Phys. Rev.
A model reduction method for biochemical reaction networks
Background: In this paper we propose a model reduction method for biochemical reaction networks governed by a variety of reversible and irreversible enzyme kinetic rate laws, including reversible Michaelis-Menten and Hill kinetics. The method proceeds by a stepwise reduction in the number of complexes, defined as the left and right-hand sides of the reactions in the network. It is based on the Kron reduction of the weighted Laplacian matrix, which describes the graph structure of the complexes and reactions in the network. It does not rely on prior knowledge of the dynamic behaviour of the network and hence can be automated, as we demonstrate. The reduced network has fewer complexes, reactions, variables and parameters as compared to the original network, and yet the behaviour of a preselected set of significant metabolites in the reduced network resembles that of the original network. Moreover the reduced network largely retains the structure and kinetics of the original model.
Results: We apply our method to a yeast glycolysis model and a rat liver fatty acid beta-oxidation model. When the number of state variables in the yeast model is reduced from 12 to 7, the difference between metabolite concentrations in the reduced and the full model, averaged over time and species, is only 8%. Likewise, when the number of state variables in the rat-liver beta-oxidation model is reduced from 42 to 29, the difference between the reduced model and the full model is 7.5%.
Conclusions: The method has improved our understanding of the dynamics of the two networks. We found that, contrary to the general disposition, the first few metabolites which were deleted from the network during our stepwise reduction approach, are not those with the shortest convergence times. It shows that our reduction approach performs differently from other approaches that are based on time-scale separation. The method can be used to facilitate fitting of the parameters or to embed a detailed model of interest in a more coarse-grained yet realistic environment
On perturbations of highly connected dyadic matroids
Geelen, Gerards, and Whittle [3] announced the following result: let be a prime power, and let be a proper minor-closed class of
-representable matroids, which does not contain
for sufficiently high . There exist integers
such that every vertically -connected matroid in is a
rank- perturbation of a frame matroid or the dual of a frame matroid
over . They further announced a characterization of the
perturbations through the introduction of subfield templates and frame
templates.
We show a family of dyadic matroids that form a counterexample to this
result. We offer several weaker conjectures to replace the ones in [3], discuss
consequences for some published papers, and discuss the impact of these new
conjectures on the structure of frame templates.Comment: Version 3 has a new title and a few other minor corrections; 38
pages, including a 6-page Jupyter notebook that contains SageMath code and
that is also available in the ancillary file
The compositional and evolutionary logic of metabolism
Metabolism displays striking and robust regularities in the forms of
modularity and hierarchy, whose composition may be compactly described. This
renders metabolic architecture comprehensible as a system, and suggests the
order in which layers of that system emerged. Metabolism also serves as the
foundation in other hierarchies, at least up to cellular integration including
bioenergetics and molecular replication, and trophic ecology. The
recapitulation of patterns first seen in metabolism, in these higher levels,
suggests metabolism as a source of causation or constraint on many forms of
organization in the biosphere.
We identify as modules widely reused subsets of chemicals, reactions, or
functions, each with a conserved internal structure. At the small molecule
substrate level, module boundaries are generally associated with the most
complex reaction mechanisms and the most conserved enzymes. Cofactors form a
structurally and functionally distinctive control layer over the small-molecule
substrate. Complex cofactors are often used at module boundaries of the
substrate level, while simpler ones participate in widely used reactions.
Cofactor functions thus act as "keys" that incorporate classes of organic
reactions within biochemistry.
The same modules that organize the compositional diversity of metabolism are
argued to have governed long-term evolution. Early evolution of core
metabolism, especially carbon-fixation, appears to have required few
innovations among a small number of conserved modules, to produce adaptations
to simple biogeochemical changes of environment. We demonstrate these features
of metabolism at several levels of hierarchy, beginning with the small-molecule
substrate and network architecture, continuing with cofactors and key conserved
reactions, and culminating in the aggregation of multiple diverse physical and
biochemical processes in cells.Comment: 56 pages, 28 figure
Asymptotology of Chemical Reaction Networks
The concept of the limiting step is extended to the asymptotology of
multiscale reaction networks. Complete theory for linear networks with well
separated reaction rate constants is developed. We present algorithms for
explicit approximations of eigenvalues and eigenvectors of kinetic matrix.
Accuracy of estimates is proven. Performance of the algorithms is demonstrated
on simple examples. Application of algorithms to nonlinear systems is
discussed.Comment: 23 pages, 8 figures, 84 refs, Corrected Journal Versio
A minimal mathematical model of nonphotochemical quenching of chlorophyll fluorescence
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.Peer reviewedPreprin
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