8,645 research outputs found
Data-driven modelling of biological multi-scale processes
Biological processes involve a variety of spatial and temporal scales. A
holistic understanding of many biological processes therefore requires
multi-scale models which capture the relevant properties on all these scales.
In this manuscript we review mathematical modelling approaches used to describe
the individual spatial scales and how they are integrated into holistic models.
We discuss the relation between spatial and temporal scales and the implication
of that on multi-scale modelling. Based upon this overview over
state-of-the-art modelling approaches, we formulate key challenges in
mathematical and computational modelling of biological multi-scale and
multi-physics processes. In particular, we considered the availability of
analysis tools for multi-scale models and model-based multi-scale data
integration. We provide a compact review of methods for model-based data
integration and model-based hypothesis testing. Furthermore, novel approaches
and recent trends are discussed, including computation time reduction using
reduced order and surrogate models, which contribute to the solution of
inference problems. We conclude the manuscript by providing a few ideas for the
development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and
Multiscale Dynamics (American Scientific Publishers
Deriving mesoscopic models of collective behaviour for finite populations
Animal groups exhibit emergent properties that are a consequence of local
interactions. Linking individual-level behaviour to coarse-grained descriptions
of animal groups has been a question of fundamental interest. Here, we present
two complementary approaches to deriving coarse-grained descriptions of
collective behaviour at so-called mesoscopic scales, which account for the
stochasticity arising from the finite sizes of animal groups. We construct
stochastic differential equations (SDEs) for a coarse-grained variable that
describes the order/consensus within a group. The first method of construction
is based on van Kampen's system-size expansion of transition rates. The second
method employs Gillespie's chemical Langevin equations. We apply these two
methods to two microscopic models from the literature, in which organisms
stochastically interact and choose between two directions/choices of foraging.
These `binary-choice' models differ only in the types of interactions between
individuals, with one assuming simple pair-wise interactions, and the other
incorporating higher-order effects. In both cases, the derived mesoscopic SDEs
have multiplicative, or state-dependent, noise. However, the different models
demonstrate the contrasting effects of noise: increasing order in the pair-wise
interaction model, whilst reducing order in the higher-order interaction model.
Although both methods yield identical SDEs for such binary-choice, or
one-dimensional, systems, the relative tractability of the chemical Langevin
approach is beneficial in generalizations to higher-dimensions. In summary,
this book chapter provides a pedagogical review of two complementary methods to
construct mesoscopic descriptions from microscopic rules and demonstrates how
resultant multiplicative noise can have counter-intuitive effects on shaping
collective behaviour.Comment: Second version, 4 figures, 2 appendice
Modeling and simulating chemical reactions
Many students are familiar with the idea of modeling chemical reactions in terms of ordinary differential equations. However, these deterministic reaction rate equations are really a certain large-scale limit of a sequence of finer-scale probabilistic models. In studying this hierarchy of models, students can be exposed to a range of modern ideas in applied and computational mathematics. This article introduces some of the basic concepts in an accessible manner and points to some challenges that currently occupy researchers in this area. Short, downloadable MATLAB codes are listed and described
Partial differential equations for self-organization in cellular and developmental biology
Understanding the mechanisms governing and regulating the emergence of structure and heterogeneity within cellular systems, such as the developing embryo, represents a multiscale challenge typifying current integrative biology research, namely, explaining the macroscale behaviour of a system from microscale dynamics. This review will focus upon modelling how cell-based dynamics orchestrate the emergence of higher level structure. After surveying representative biological examples and the models used to describe them, we will assess how developments at the scale of molecular biology have impacted on current theoretical frameworks, and the new modelling opportunities that are emerging as a result. We shall restrict our survey of mathematical approaches to partial differential equations and the tools required for their analysis. We will discuss the gap between the modelling abstraction and biological reality, the challenges this presents and highlight some open problems in the field
Noise-Induced Spatial Pattern Formation in Stochastic Reaction-Diffusion Systems
This paper is concerned with stochastic reaction-diffusion kinetics governed
by the reaction-diffusion master equation. Specifically, the primary goal of
this paper is to provide a mechanistic basis of Turing pattern formation that
is induced by intrinsic noise. To this end, we first derive an approximate
reaction-diffusion system by using linear noise approximation. We show that the
approximated system has a certain structure that is associated with a coupled
dynamic multi-agent system. This observation then helps us derive an efficient
computation tool to examine the spatial power spectrum of the intrinsic noise.
We numerically demonstrate that the result is quite effective to analyze
noise-induced Turing pattern. Finally, we illustrate the theoretical mechanism
behind the noise-induced pattern formation with a H2 norm interpretation of the
multi-agent system
The Role of Regulated mRNA Stability in Establishing Bicoid Morphogen Gradient in Drosophila Embryonic Development
The Bicoid morphogen is amongst the earliest triggers of differential spatial pattern of gene expression and subsequent cell fate determination in the embryonic development of Drosophila. This maternally deposited morphogen is thought to diffuse in the embryo, establishing a concentration gradient which is sensed by downstream genes. In most model based analyses of this process, the translation of the bicoid mRNA is thought to take place at a fixed rate from the anterior pole of the embryo and a supply of the resulting protein at a constant rate is assumed. Is this process of morphogen generation a passive one as assumed in the modelling literature so far, or would available data support an alternate hypothesis that the stability of the mRNA is regulated by active processes? We introduce a model in which the stability of the maternal mRNA is regulated by being held constant for a length of time, followed by rapid degradation. With this more realistic model of the source, we have analysed three computational models of spatial morphogen propagation along the anterior-posterior axis: (a) passive diffusion modelled as a deterministic differential equation, (b) diffusion enhanced by a cytoplasmic flow term; and (c) diffusion modelled by stochastic simulation of the corresponding chemical reactions. Parameter estimation on these models by matching to publicly available data on spatio-temporal Bicoid profiles suggests strong support for regulated stability over either a constant supply rate or one where the maternal mRNA is permitted to degrade in a passive manner
Intrinsic noise profoundly alters the dynamics and steady state of morphogen-controlled bistable genetic switches
During tissue development, patterns of gene expression determine the spatial
arrangement of cell types. In many cases, gradients of secreted signaling
molecules - morphogens - guide this process. The continuous positional
information provided by the gradient is converted into discrete cell types by
the downstream transcriptional network that responds to the morphogen. A
mechanism commonly used to implement a sharp transition between two adjacent
cell fates is the genetic toggle switch, composed of cross-repressing
transcriptional determinants. Previous analyses emphasize the steady state
output of these mechanisms. Here, we explore the dynamics of the toggle switch
and use exact numerical simulations of the kinetic reactions, the Chemical
Langevin Equation, and Minimum Action Path theory to establish a framework for
studying the effect of gene expression noise on patterning time and boundary
position. This provides insight into the time scale, gene expression
trajectories and directionality of stochastic switching events between cell
states. Taking gene expression noise into account predicts that the final
boundary position of a morphogen-induced toggle switch, although robust to
changes in the details of the noise, is distinct from that of the deterministic
system. Moreover, stochastic switching introduces differences in patterning
time along the morphogen gradient that result in a patterning wave propagating
away from the morphogen source. The velocity of this wave is influenced by
noise; the wave sharpens and slows as it advances and may never reach steady
state in a biologically relevant time. This could explain experimentally
observed dynamics of pattern formation. Together the analysis reveals the
importance of dynamical transients for understanding morphogen-driven
transcriptional networks and indicates that gene expression noise can
qualitatively alter developmental patterning
Mesoscopic and continuum modelling of angiogenesis
Angiogenesis is the formation of new blood vessels from pre-existing ones in
response to chemical signals secreted by, for example, a wound or a tumour. In
this paper, we propose a mesoscopic lattice-based model of angiogenesis, in
which processes that include proliferation and cell movement are considered as
stochastic events. By studying the dependence of the model on the lattice
spacing and the number of cells involved, we are able to derive the
deterministic continuum limit of our equations and compare it to similar
existing models of angiogenesis. We further identify conditions under which the
use of continuum models is justified, and others for which stochastic or
discrete effects dominate. We also compare different stochastic models for the
movement of endothelial tip cells which have the same macroscopic,
deterministic behaviour, but lead to markedly different behaviour in terms of
production of new vessel cells.Comment: 48 pages, 13 figure
Modelling biological invasions: individual to population scales at interfaces
Extracting the population level behaviour of biological systems from that of the individual is critical in understanding dynamics across multiple scales and thus has been the subject of numerous investigations. Here, the influence of spatial heterogeneity in such contexts is explored for interfaces with a separation of the length scales characterising the individual and the interface, a situation that can arise in applications involving cellular modelling. As an illustrative example, we consider cell movement between white and grey matter in the brain which may be relevant in considering the invasive dynamics of glioma. We show that while one can safely neglect intrinsic noise, at least when considering glioma cell invasion, profound differences in population behaviours emerge in the presence of interfaces with only subtle alterations in the dynamics at the individual level. Transport driven by local cell sensing generates predictions of cell accumulations along interfaces where cell motility changes. This behaviour is not predicted with the commonly used Fickian diffusion transport model, but can be extracted from preliminary observations of specific cell lines in recent, novel, cryo-imaging. Consequently, these findings suggest a need to consider the impact of individual behaviour, spatial heterogeneity and especially interfaces in experimental and modelling frameworks of cellular dynamics, for instance in the characterisation of glioma cell motility
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