94,455 research outputs found
On Projection-Based Model Reduction of Biochemical Networks-- Part I: The Deterministic Case
This paper addresses the problem of model reduction for dynamical system
models that describe biochemical reaction networks. Inherent in such models are
properties such as stability, positivity and network structure. Ideally these
properties should be preserved by model reduction procedures, although
traditional projection based approaches struggle to do this. We propose a
projection based model reduction algorithm which uses generalised block
diagonal Gramians to preserve structure and positivity. Two algorithms are
presented, one provides more accurate reduced order models, the second provides
easier to simulate reduced order models. The results are illustrated through
numerical examples.Comment: Submitted to 53rd IEEE CD
Learning Petri net models of non-linear gene interactions
Understanding how an individual's genetic make-up influences their risk of disease is a problem of paramount importance. Although machine-learning techniques are able to uncover the relationships between genotype and disease, the problem of automatically building the best biochemical model or “explanation” of the relationship has received less attention. In this paper, I describe a method based on random hill climbing that automatically builds Petri net models of non-linear (or multi-factorial) disease-causing gene–gene interactions. Petri nets are a suitable formalism for this problem, because they are used to model concurrent, dynamic processes analogous to biochemical reaction networks. I show that this method is routinely able to identify perfect Petri net models for three disease-causing gene–gene interactions recently reported in the literature
Emergence of switch-like behavior in a large family of simple biochemical networks
Bistability plays a central role in the gene regulatory networks (GRNs)
controlling many essential biological functions, including cellular
differentiation and cell cycle control. However, establishing the network
topologies that can exhibit bistability remains a challenge, in part due to the
exceedingly large variety of GRNs that exist for even a small number of
components. We begin to address this problem by employing chemical reaction
network theory in a comprehensive in silico survey to determine the capacity
for bistability of more than 40,000 simple networks that can be formed by two
transcription factor-coding genes and their associated proteins (assuming only
the most elementary biochemical processes). We find that there exist reaction
rate constants leading to bistability in ~90% of these GRN models, including
several circuits that do not contain any of the TF cooperativity commonly
associated with bistable systems, and the majority of which could only be
identified as bistable through an original subnetwork-based analysis. A
topological sorting of the two-gene family of networks based on the presence or
absence of biochemical reactions reveals eleven minimal bistable networks
(i.e., bistable networks that do not contain within them a smaller bistable
subnetwork). The large number of previously unknown bistable network topologies
suggests that the capacity for switch-like behavior in GRNs arises with
relative ease and is not easily lost through network evolution. To highlight
the relevance of the systematic application of CRNT to bistable network
identification in real biological systems, we integrated publicly available
protein-protein interaction, protein-DNA interaction, and gene expression data
from Saccharomyces cerevisiae, and identified several GRNs predicted to behave
in a bistable fashion.Comment: accepted to PLoS Computational Biolog
Efficient Finite Difference Method for Computing Sensitivities of Biochemical Reactions
Sensitivity analysis of biochemical reactions aims at quantifying the
dependence of the reaction dynamics on the reaction rates. The computation of
the parameter sensitivities, however, poses many computational challenges when
taking stochastic noise into account. This paper proposes a new finite
difference method for efficiently computing sensitivities of biochemical
reactions. We employ propensity bounds of reactions to couple the simulation of
the nominal and perturbed processes. The exactness of the simulation is
reserved by applying the rejection-based mechanism. For each simulation step,
the nominal and perturbed processes under our coupling strategy are
synchronized and often jump together, increasing their positive correlation and
hence reducing the variance of the estimator. The distinctive feature of our
approach in comparison with existing coupling approaches is that it only needs
to maintain a single data structure storing propensity bounds of reactions
during the simulation of the nominal and perturbed processes. Our approach
allows to computing sensitivities of many reaction rates simultaneously.
Moreover, the data structure does not require to be updated frequently, hence
improving the computational cost. This feature is especially useful when
applied to large reaction networks. We benchmark our method on biological
reaction models to prove its applicability and efficiency.Comment: 29 pages with 6 figures, 2 table
SBML models and MathSBML
MathSBML is an open-source, freely-downloadable Mathematica package that facilitates working with Systems Biology Markup Language (SBML) models. SBML is a toolneutral,computer-readable format for representing models of biochemical reaction networks, applicable to metabolic networks, cell-signaling pathways, genomic regulatory networks, and other modeling problems in systems biology that is widely supported by the systems biology community. SBML is based on XML, a standard medium for representing and transporting data that is widely supported on the internet as well as in computational biology and bioinformatics. Because SBML is tool-independent, it enables model transportability, reuse, publication and survival. In addition to MathSBML, a number of other tools that support SBML model examination and manipulation are provided on the sbml.org website, including libSBML, a C/C++ library for reading SBML models; an SBML Toolbox for MatLab; file conversion programs; an SBML model validator and visualizer; and SBML specifications and schemas. MathSBML enables SBML file import to and export from Mathematica as well as providing an API for model manipulation and simulation
Good Learning and Implicit Model Enumeration
MathSBML is an open-source, freely-downloadable Mathematica package that facilitates working with Systems Biology Markup Language (SBML) models. SBML is a toolneutral,computer-readable format for representing models of biochemical reaction networks, applicable to metabolic networks, cell-signaling pathways, genomic regulatory networks, and other modeling problems in systems biology that is widely supported by the systems biology community. SBML is based on XML, a standard medium for representing and transporting data that is widely supported on the internet as well as in computational biology and bioinformatics. Because SBML is tool-independent, it enables model transportability, reuse, publication and survival. In addition to MathSBML, a number of other tools that support SBML model examination and manipulation are provided on the sbml.org website, including libSBML, a C/C++ library for reading SBML models; an SBML Toolbox for MatLab; file conversion programs; an SBML model validator and visualizer; and SBML specifications and schemas. MathSBML enables SBML file import to and export from Mathematica as well as providing an API for model manipulation and simulation
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