5,255 research outputs found
Basins of Attraction, Commitment Sets and Phenotypes of Boolean Networks
The attractors of Boolean networks and their basins have been shown to be
highly relevant for model validation and predictive modelling, e.g., in systems
biology. Yet there are currently very few tools available that are able to
compute and visualise not only attractors but also their basins. In the realm
of asynchronous, non-deterministic modeling not only is the repertoire of
software even more limited, but also the formal notions for basins of
attraction are often lacking. In this setting, the difficulty both for theory
and computation arises from the fact that states may be ele- ments of several
distinct basins. In this paper we address this topic by partitioning the state
space into sets that are committed to the same attractors. These commitment
sets can easily be generalised to sets that are equivalent w.r.t. the long-term
behaviours of pre-selected nodes which leads us to the notions of markers and
phenotypes which we illustrate in a case study on bladder tumorigenesis. For
every concept we propose equivalent CTL model checking queries and an extension
of the state of the art model checking software NuSMV is made available that is
capa- ble of computing the respective sets. All notions are fully integrated as
three new modules in our Python package PyBoolNet, including functions for
visualising the basins, commitment sets and phenotypes as quotient graphs and
pie charts
Dynamical and Structural Modularity of Discrete Regulatory Networks
A biological regulatory network can be modeled as a discrete function that
contains all available information on network component interactions. From this
function we can derive a graph representation of the network structure as well
as of the dynamics of the system. In this paper we introduce a method to
identify modules of the network that allow us to construct the behavior of the
given function from the dynamics of the modules. Here, it proves useful to
distinguish between dynamical and structural modules, and to define network
modules combining aspects of both. As a key concept we establish the notion of
symbolic steady state, which basically represents a set of states where the
behavior of the given function is in some sense predictable, and which gives
rise to suitable network modules. We apply the method to a regulatory network
involved in T helper cell differentiation
ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra
Background: Many biological systems are modeled qualitatively with discrete
models, such as probabilistic Boolean networks, logical models, Petri nets, and
agent-based models, with the goal to gain a better understanding of the system.
The computational complexity to analyze the complete dynamics of these models
grows exponentially in the number of variables, which impedes working with
complex models. Although there exist sophisticated algorithms to determine the
dynamics of discrete models, their implementations usually require
labor-intensive formatting of the model formulation, and they are oftentimes
not accessible to users without programming skills. Efficient analysis methods
are needed that are accessible to modelers and easy to use. Method: By
converting discrete models into algebraic models, tools from computational
algebra can be used to analyze their dynamics. Specifically, we propose a
method to identify attractors of a discrete model that is equivalent to solving
a system of polynomial equations, a long-studied problem in computer algebra.
Results: A method for efficiently identifying attractors, and the web-based
tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other
analysis methods for discrete models. ADAM converts several discrete model
types automatically into polynomial dynamical systems and analyzes their
dynamics using tools from computer algebra. Based on extensive experimentation
with both discrete models arising in systems biology and randomly generated
networks, we found that the algebraic algorithms presented in this manuscript
are fast for systems with the structure maintained by most biological systems,
namely sparseness, i.e., while the number of nodes in a biological network may
be quite large, each node is affected only by a small number of other nodes,
and robustness, i.e., small number of attractors
A tool for model-checking Markov chains
Markov chains are widely used in the context of the performance and reliability modeling of various systems. Model checking of such chains with respect to a given (branching) temporal logic formula has been proposed for both discrete [34, 10] and continuous time settings [7, 12]. In this paper, we describe a prototype model checker for discrete and continuous-time Markov chains, the Erlangen-Twente Markov Chain Checker EÎMC2, where properties are expressed in appropriate extensions of CTL. We illustrate the general benefits of this approach and discuss the structure of the tool. Furthermore, we report on successful applications of the tool to some examples, highlighting lessons learned during the development and application of EÎMC2
A Mathematical Framework for Agent Based Models of Complex Biological Networks
Agent-based modeling and simulation is a useful method to study biological
phenomena in a wide range of fields, from molecular biology to ecology. Since
there is currently no agreed-upon standard way to specify such models it is not
always easy to use published models. Also, since model descriptions are not
usually given in mathematical terms, it is difficult to bring mathematical
analysis tools to bear, so that models are typically studied through
simulation. In order to address this issue, Grimm et al. proposed a protocol
for model specification, the so-called ODD protocol, which provides a standard
way to describe models. This paper proposes an addition to the ODD protocol
which allows the description of an agent-based model as a dynamical system,
which provides access to computational and theoretical tools for its analysis.
The mathematical framework is that of algebraic models, that is, time-discrete
dynamical systems with algebraic structure. It is shown by way of several
examples how this mathematical specification can help with model analysis.Comment: To appear in Bulletin of Mathematical Biolog
Petri nets for systems and synthetic biology
We give a description of a Petri net-based framework for
modelling and analysing biochemical pathways, which uni¯es the qualita-
tive, stochastic and continuous paradigms. Each perspective adds its con-
tribution to the understanding of the system, thus the three approaches
do not compete, but complement each other. We illustrate our approach
by applying it to an extended model of the three stage cascade, which
forms the core of the ERK signal transduction pathway. Consequently
our focus is on transient behaviour analysis. We demonstrate how quali-
tative descriptions are abstractions over stochastic or continuous descrip-
tions, and show that the stochastic and continuous models approximate
each other. Although our framework is based on Petri nets, it can be
applied more widely to other formalisms which are used to model and
analyse biochemical networks
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