57,886 research outputs found
A structured approach for the engineering of biochemical network models, illustrated for signalling pathways
http://dx.doi.org/10.1093/bib/bbn026Quantitative models of biochemical networks (signal transduction cascades, metabolic pathways, gene regulatory circuits) are a central component of modern systems biology. Building and managing these complex models is a major challenge that can benefit from the application of formal methods adopted from theoretical computing science. Here we provide a general introduction to the field of formal modelling, which emphasizes the intuitive biochemical basis of the modelling process, but is also accessible for an audience with a background in computing science and/or model engineering. We show how signal transduction cascades can be modelled in a modular fashion, using both a qualitative approach { Qualitative Petri nets, and quantitative approaches { Continuous Petri Nets and Ordinary Differential Equations. We review the major elementary building blocks of a cellular signalling model, discuss which critical design decisions have to be made during model building, and present ..
Evolution and development of complex computational systems using the paradigm of metabolic computing in Epigenetic Tracking
Epigenetic Tracking (ET) is an Artificial Embryology system which allows for
the evolution and development of large complex structures built from artificial
cells. In terms of the number of cells, the complexity of the bodies generated
with ET is comparable with the complexity of biological organisms. We have
previously used ET to simulate the growth of multicellular bodies with
arbitrary 3-dimensional shapes which perform computation using the paradigm of
"metabolic computing". In this paper we investigate the memory capacity of such
computational structures and analyse the trade-off between shape and
computation. We now plan to build on these foundations to create a
biologically-inspired model in which the encoding of the phenotype is efficient
(in terms of the compactness of the genome) and evolvable in tasks involving
non-trivial computation, robust to damage and capable of self-maintenance and
self-repair.Comment: In Proceedings Wivace 2013, arXiv:1309.712
Signatures of arithmetic simplicity in metabolic network architecture
Metabolic networks perform some of the most fundamental functions in living
cells, including energy transduction and building block biosynthesis. While
these are the best characterized networks in living systems, understanding
their evolutionary history and complex wiring constitutes one of the most
fascinating open questions in biology, intimately related to the enigma of
life's origin itself. Is the evolution of metabolism subject to general
principles, beyond the unpredictable accumulation of multiple historical
accidents? Here we search for such principles by applying to an artificial
chemical universe some of the methodologies developed for the study of genome
scale models of cellular metabolism. In particular, we use metabolic flux
constraint-based models to exhaustively search for artificial chemistry
pathways that can optimally perform an array of elementary metabolic functions.
Despite the simplicity of the model employed, we find that the ensuing pathways
display a surprisingly rich set of properties, including the existence of
autocatalytic cycles and hierarchical modules, the appearance of universally
preferable metabolites and reactions, and a logarithmic trend of pathway length
as a function of input/output molecule size. Some of these properties can be
derived analytically, borrowing methods previously used in cryptography. In
addition, by mapping biochemical networks onto a simplified carbon atom
reaction backbone, we find that several of the properties predicted by the
artificial chemistry model hold for real metabolic networks. These findings
suggest that optimality principles and arithmetic simplicity might lie beneath
some aspects of biochemical complexity
An analytic approximation of the feasible space of metabolic networks
Assuming a steady-state condition within a cell, metabolic fluxes satisfy an
under-determined linear system of stoichiometric equations. Characterizing the
space of fluxes that satisfy such equations along with given bounds (and
possibly additional relevant constraints) is considered of utmost importance
for the understanding of cellular metabolism. Extreme values for each
individual flux can be computed with Linear Programming (as Flux Balance
Analysis), and their marginal distributions can be approximately computed with
Monte-Carlo sampling. Here we present an approximate analytic method for the
latter task based on Expectation Propagation equations that does not involve
sampling and can achieve much better predictions than other existing analytic
methods. The method is iterative, and its computation time is dominated by one
matrix inversion per iteration. With respect to sampling, we show through
extensive simulation that it has some advantages including computation time,
and the ability to efficiently fix empirically estimated distributions of
fluxes
MetExploreViz: web component for interactive metabolic network visualization
Summary: MetExploreViz is an open source web component that can be easily embedded in any
web site. It provides features dedicated to the visualization of metabolic networks and pathways
and thus offers a flexible solution to analyse omics data in a biochemical context.
Availability and implementation: Documentation and link to GIT code repository (GPL 3.0 license)
are available at this URL: http://metexplore.toulouse.inra.fr/metexploreViz/doc
Computation of elementary modes: a unifying framework and the new binary approach
BACKGROUND: Metabolic pathway analysis has been recognized as a central approach to the structural analysis of metabolic networks. The concept of elementary (flux) modes provides a rigorous formalism to describe and assess pathways and has proven to be valuable for many applications. However, computing elementary modes is a hard computational task. In recent years we assisted in a multiplication of algorithms dedicated to it. We require a summarizing point of view and a continued improvement of the current methods. RESULTS: We show that computing the set of elementary modes is equivalent to computing the set of extreme rays of a convex cone. This standard mathematical representation provides a unified framework that encompasses the most prominent algorithmic methods that compute elementary modes and allows a clear comparison between them. Taking lessons from this benchmark, we here introduce a new method, the binary approach, which computes the elementary modes as binary patterns of participating reactions from which the respective stoichiometric coefficients can be computed in a post-processing step. We implemented the binary approach in FluxAnalyzer 5.1, a software that is free for academics. The binary approach decreases the memory demand up to 96% without loss of speed giving the most efficient method available for computing elementary modes to date. CONCLUSIONS: The equivalence between elementary modes and extreme ray computations offers opportunities for employing tools from polyhedral computation for metabolic pathway analysis. The new binary approach introduced herein was derived from this general theoretical framework and facilitates the computation of elementary modes in considerably larger networks
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