8,333 research outputs found
Qualitative modelling and analysis of regulations in multi-cellular systems using Petri nets and topological collections
In this paper, we aim at modelling and analyzing the regulation processes in
multi-cellular biological systems, in particular tissues.
The modelling framework is based on interconnected logical regulatory
networks a la Rene Thomas equipped with information about their spatial
relationships. The semantics of such models is expressed through colored Petri
nets to implement regulation rules, combined with topological collections to
implement the spatial information.
Some constraints are put on the the representation of spatial information in
order to preserve the possibility of an enumerative and exhaustive state space
exploration.
This paper presents the modelling framework, its semantics, as well as a
prototype implementation that allowed preliminary experimentation on some
applications.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
Abstracting Asynchronous Multi-Valued Networks: An Initial Investigation
Multi-valued networks provide a simple yet expressive qualitative state based
modelling approach for biological systems. In this paper we develop an
abstraction theory for asynchronous multi-valued network models that allows the
state space of a model to be reduced while preserving key properties of the
model. The abstraction theory therefore provides a mechanism for coping with
the state space explosion problem and supports the analysis and comparison of
multi-valued networks. We take as our starting point the abstraction theory for
synchronous multi-valued networks which is based on the finite set of traces
that represent the behaviour of such a model. The problem with extending this
approach to the asynchronous case is that we can now have an infinite set of
traces associated with a model making a simple trace inclusion test infeasible.
To address this we develop a decision procedure for checking asynchronous
abstractions based on using the finite state graph of an asynchronous
multi-valued network to reason about its trace semantics. We illustrate the
abstraction techniques developed by considering a detailed case study based on
a multi-valued network model of the regulation of tryptophan biosynthesis in
Escherichia coli.Comment: Presented at MeCBIC 201
Logical modelling of cellular decision processes with GINsim
International audienc
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
On the basic computational structure of gene regulatory networks
Gene regulatory networks constitute the first layer of the cellular
computation for cell adaptation and surveillance. In these webs, a set of
causal relations is built up from thousands of interactions between
transcription factors and their target genes. The large size of these webs and
their entangled nature make difficult to achieve a global view of their
internal organisation. Here, this problem has been addressed through a
comparative study for {\em Escherichia coli}, {\em Bacillus subtilis} and {\em
Saccharomyces cerevisiae} gene regulatory networks. We extract the minimal core
of causal relations, uncovering the hierarchical and modular organisation from
a novel dynamical/causal perspective. Our results reveal a marked top-down
hierarchy containing several small dynamical modules for \textit{E. coli} and
\textit{B. subtilis}. Conversely, the yeast network displays a single but large
dynamical module in the middle of a bow-tie structure. We found that these
dynamical modules capture the relevant wiring among both common and
organism-specific biological functions such as transcription initiation,
metabolic control, signal transduction, response to stress, sporulation and
cell cycle. Functional and topological results suggest that two fundamentally
different forms of logic organisation may have evolved in bacteria and yeast.Comment: This article is published at Molecular Biosystems, Please cite as:
Carlos Rodriguez-Caso, Bernat Corominas-Murtra and Ricard V. Sole. Mol.
BioSyst., 2009, 5 pp 1617--171
Computational core and fixed-point organisation in Boolean networks
In this paper, we analyse large random Boolean networks in terms of a
constraint satisfaction problem. We first develop an algorithmic scheme which
allows to prune simple logical cascades and under-determined variables,
returning thereby the computational core of the network. Second we apply the
cavity method to analyse number and organisation of fixed points. We find in
particular a phase transition between an easy and a complex regulatory phase,
the latter one being characterised by the existence of an exponential number of
macroscopically separated fixed-point clusters. The different techniques
developed are reinterpreted as algorithms for the analysis of single Boolean
networks, and they are applied to analysis and in silico experiments on the
gene-regulatory networks of baker's yeast (saccaromices cerevisiae) and the
segment-polarity genes of the fruit-fly drosophila melanogaster.Comment: 29 pages, 18 figures, version accepted for publication in JSTA
SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools
Background:
Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing.
Results:
We present the Systems Biology Markup Language (SBML) Qualitative Models Package (âqualâ), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models.
Conclusions:
SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks
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