4,134 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
A Bayesian approach for inferring neuronal connectivity from calcium fluorescent imaging data
Deducing the structure of neural circuits is one of the central problems of
modern neuroscience. Recently-introduced calcium fluorescent imaging methods
permit experimentalists to observe network activity in large populations of
neurons, but these techniques provide only indirect observations of neural
spike trains, with limited time resolution and signal quality. In this work we
present a Bayesian approach for inferring neural circuitry given this type of
imaging data. We model the network activity in terms of a collection of coupled
hidden Markov chains, with each chain corresponding to a single neuron in the
network and the coupling between the chains reflecting the network's
connectivity matrix. We derive a Monte Carlo Expectation--Maximization
algorithm for fitting the model parameters; to obtain the sufficient statistics
in a computationally-efficient manner, we introduce a specialized
blockwise-Gibbs algorithm for sampling from the joint activity of all observed
neurons given the observed fluorescence data. We perform large-scale
simulations of randomly connected neuronal networks with biophysically
realistic parameters and find that the proposed methods can accurately infer
the connectivity in these networks given reasonable experimental and
computational constraints. In addition, the estimation accuracy may be improved
significantly by incorporating prior knowledge about the sparseness of
connectivity in the network, via standard L penalization methods.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS303 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Colorectal Cancer Through Simulation and Experiment
Colorectal cancer has continued to generate a huge amount of research interest over several decades, forming a canonical example of tumourigenesis since its use in Fearon and Vogelstein’s linear model of genetic mutation. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical biology and computer-based modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the ‘Hallmarks of Cancer’ has been extended in recent times and provides an excellent basis for future research. We present a timely summary of the literature relating to colorectal cancer, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. We conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that mathematical and computational modelling can provide
Neurovascular coupling: insights from multi-modal dynamic causal modelling of fMRI and MEG
This technical note presents a framework for investigating the underlying
mechanisms of neurovascular coupling in the human brain using multi-modal
magnetoencephalography (MEG) and functional magnetic resonance (fMRI)
neuroimaging data. This amounts to estimating the evidence for several
biologically informed models of neurovascular coupling using variational
Bayesian methods and selecting the most plausible explanation using Bayesian
model comparison. First, fMRI data is used to localise active neuronal sources.
The coordinates of neuronal sources are then used as priors in the
specification of a DCM for MEG, in order to estimate the underlying generators
of the electrophysiological responses. The ensuing estimates of neuronal
parameters are used to generate neuronal drive functions, which model the pre
or post synaptic responses to each experimental condition in the fMRI paradigm.
These functions form the input to a model of neurovascular coupling, the
parameters of which are estimated from the fMRI data. This establishes a
Bayesian fusion technique that characterises the BOLD response - asking, for
example, whether instantaneous or delayed pre or post synaptic signals mediate
haemodynamic responses. Bayesian model comparison is used to identify the most
plausible hypotheses about the causes of the multimodal data. We illustrate
this procedure by comparing a set of models of a single-subject auditory fMRI
and MEG dataset. Our exemplar analysis suggests that the origin of the BOLD
signal is mediated instantaneously by intrinsic neuronal dynamics and that
neurovascular coupling mechanisms are region-specific. The code and example
dataset associated with this technical note are available through the
statistical parametric mapping (SPM) software package
Engineering simulations for cancer systems biology
Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions
Systems biology in animal sciences
Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed ‘omics’ technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A ‘system’ approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with ‘system approaches’ in animal sciences, providing exciting opportunities to predict and modulate animal traits
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