5,276 research outputs found
Compositionality, stochasticity and cooperativity in dynamic models of gene regulation
We present an approach for constructing dynamic models for the simulation of
gene regulatory networks from simple computational elements. Each element is
called a ``gene gate'' and defines an input/output-relationship corresponding
to the binding and production of transcription factors. The proposed reaction
kinetics of the gene gates can be mapped onto stochastic processes and the
standard ode-description. While the ode-approach requires fixing the system's
topology before its correct implementation, expressing them in stochastic
pi-calculus leads to a fully compositional scheme: network elements become
autonomous and only the input/output relationships fix their wiring. The
modularity of our approach allows to pass easily from a basic first-level
description to refined models which capture more details of the biological
system. As an illustrative application we present the stochastic repressilator,
an artificial cellular clock, which oscillates readily without any cooperative
effects.Comment: 15 pages, 8 figures. Accepted by the HFSP journal (13/09/07
BlenX-based compositional modeling of complex reaction mechanisms
Molecular interactions are wired in a fascinating way resulting in complex
behavior of biological systems. Theoretical modeling provides a useful
framework for understanding the dynamics and the function of such networks. The
complexity of the biological networks calls for conceptual tools that manage
the combinatorial explosion of the set of possible interactions. A suitable
conceptual tool to attack complexity is compositionality, already successfully
used in the process algebra field to model computer systems. We rely on the
BlenX programming language, originated by the beta-binders process calculus, to
specify and simulate high-level descriptions of biological circuits. The
Gillespie's stochastic framework of BlenX requires the decomposition of
phenomenological functions into basic elementary reactions. Systematic
unpacking of complex reaction mechanisms into BlenX templates is shown in this
study. The estimation/derivation of missing parameters and the challenges
emerging from compositional model building in stochastic process algebras are
discussed. A biological example on circadian clock is presented as a case study
of BlenX compositionality
Investigating modularity in the analysis of process algebra models of biochemical systems
Compositionality is a key feature of process algebras which is often cited as
one of their advantages as a modelling technique. It is certainly true that in
biochemical systems, as in many other systems, model construction is made
easier in a formalism which allows the problem to be tackled compositionally.
In this paper we consider the extent to which the compositional structure which
is inherent in process algebra models of biochemical systems can be exploited
during model solution. In essence this means using the compositional structure
to guide decomposed solution and analysis.
Unfortunately the dynamic behaviour of biochemical systems exhibits strong
interdependencies between the components of the model making decomposed
solution a difficult task. Nevertheless we believe that if such decomposition
based on process algebras could be established it would demonstrate substantial
benefits for systems biology modelling. In this paper we present our
preliminary investigations based on a case study of the pheromone pathway in
yeast, modelling in the stochastic process algebra Bio-PEPA
Context in Synthetic Biology: Memory Effects of Environments with Mono-molecular Reactions
Synthetic biology aims at designing modular genetic circuits that can be
assembled according to the desired function. When embedded in a cell, a circuit
module becomes a small subnetwork within a larger environmental network, and
its dynamics is therefore affected by potentially unknown interactions with the
environment. It is well-known that the presence of the environment not only
causes extrinsic noise but also memory effects, which means that the dynamics
of the subnetwork is affected by its past states via a memory function that is
characteristic of the environment. We study several generic scenarios for the
coupling between a small module and a larger environment, with the environment
consisting of a chain of mono-molecular reactions. By mapping the dynamics of
this coupled system onto random walks, we are able to give exact analytical
expressions for the arising memory functions. Hence, our results give insights
into the possible types of memory functions and thereby help to better predict
subnetwork dynamics.Comment: 14 pages, 6 figures Accepted Versio
Formal executable descriptions of biological systems
The similarities between systems of living entities and systems of concurrent processes may support biological experiments in silico. Process calculi offer a formal framework to describe biological systems, as well as to analyse their behaviour, both from a qualitative and a quantitative point of view. A couple of little examples help us in showing how this can be done. We mainly focus our attention on the qualitative and quantitative aspects of the considered biological systems, and briefly illustrate which kinds of analysis are possible. We use a known stochastic calculus for the first example. We then present some statistics collected by repeatedly running the specification, that turn out to agree with those obtained by experiments in vivo. Our second example motivates a richer calculus. Its stochastic extension requires a non trivial machinery to faithfully reflect the real dynamic behaviour of biological systems
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Fungal community assembly in drought-stressed sorghum shows stochasticity, selection, and universal ecological dynamics.
Community assembly of crop-associated fungi is thought to be strongly influenced by deterministic selection exerted by the plant host, rather than stochastic processes. Here we use a simple, sorghum system with abundant sampling to show that stochastic forces (drift or stochastic dispersal) act on fungal community assembly in leaves and roots early in host development and when sorghum is drought stressed, conditions when mycobiomes are small. Unexpectedly, we find no signal for stochasticity when drought stress is relieved, likely due to renewed selection by the host. In our experimental system, the host compartment exerts the strongest effects on mycobiome assembly, followed by the timing of plant development and lastly by plant genotype. Using a dissimilarity-overlap approach, we find a universality in the forces of community assembly of the mycobiomes of the different sorghum compartments and in functional guilds of fungi
Emergence of the mitochondrial reticulum from fission and fusion dynamics
Mitochondria form a dynamic tubular reticulum within eukaryotic cells. Currently, quantitative understanding of its morphological characteristics is largely absent, despite major progress in deciphering the molecular fission and fusion machineries shaping its structure. Here we address the principles of formation and the large-scale organization of the cell-wide network of mitochondria. On the basis of experimentally determined structural features we establish the tip-to-tip and tip-to-side fission and fusion events as dominant reactions in the motility of this organelle. Subsequently, we introduce a graph-based model of the chondriome able to encompass its inherent variability in a single framework. Using both mean-field deterministic and explicit stochastic mathematical methods we establish a relationship between the chondriome structural network characteristics and underlying kinetic rate parameters. The computational analysis indicates that mitochondrial networks exhibit a percolation threshold. Intrinsic morphological instability of the mitochondrial reticulum resulting from its vicinity to the percolation transition is proposed as a novel mechanism that can be utilized by cells for optimizing their functional competence via dynamic remodeling of the chondriome. The detailed size distribution of the network components predicted by the dynamic graph representation introduces a relationship between chondriome characteristics and cell function. It forms a basis for understanding the architecture of mitochondria as a cell-wide but inhomogeneous organelle. Analysis of the reticulum adaptive configuration offers a direct clarification for its impact on numerous physiological processes strongly dependent on mitochondrial dynamics and organization, such as efficiency of cellular metabolism, tissue differentiation and aging
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