14,578 research outputs found
Multi-level agent-based modeling - A literature survey
During last decade, multi-level agent-based modeling has received significant
and dramatically increasing interest. In this article we present a
comprehensive and structured review of literature on the subject. We present
the main theoretical contributions and application domains of this concept,
with an emphasis on social, flow, biological and biomedical models.Comment: v2. Ref 102 added. v3-4 Many refs and text added v5-6 bibliographic
statistics updated. v7 Change of the name of the paper to reflect what it
became, many refs and text added, bibliographic statistics update
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
An integrative computational model for intestinal tissue renewal
Objectives\ud
\ud
The luminal surface of the gut is lined with a monolayer of epithelial cells that acts as a nutrient absorptive engine and protective barrier. To maintain its integrity and functionality, the epithelium is renewed every few days. Theoretical models are powerful tools that can be used to test hypotheses concerning the regulation of this renewal process, to investigate how its dysfunction can lead to loss of homeostasis and neoplasia, and to identify potential therapeutic interventions. Here we propose a new multiscale model for crypt dynamics that links phenomena occurring at the subcellular, cellular and tissue levels of organisation.\ud
\ud
Methods\ud
\ud
At the subcellular level, deterministic models characterise molecular networks, such as cell-cycle control and Wnt signalling. The output of these models determines the behaviour of each epithelial cell in response to intra-, inter- and extracellular cues. The modular nature of the model enables us to easily modify individual assumptions and analyse their effects on the system as a whole.\ud
\ud
Results\ud
\ud
We perform virtual microdissection and labelling-index experiments, evaluate the impact of various model extensions, obtain new insight into clonal expansion in the crypt, and compare our predictions with recent mitochondrial DNA mutation data. \ud
\ud
Conclusions\ud
\ud
We demonstrate that relaxing the assumption that stem-cell positions are fixed enables clonal expansion and niche succession to occur. We also predict that the presence of extracellular factors near the base of the crypt alone suffices to explain the observed spatial variation in nuclear beta-catenin levels along the crypt axis
Multiple verification in computational modeling of bone pathologies
We introduce a model checking approach to diagnose the emerging of bone
pathologies. The implementation of a new model of bone remodeling in PRISM has
led to an interesting characterization of osteoporosis as a defective bone
remodeling dynamics with respect to other bone pathologies. Our approach allows
to derive three types of model checking-based diagnostic estimators. The first
diagnostic measure focuses on the level of bone mineral density, which is
currently used in medical practice. In addition, we have introduced a novel
diagnostic estimator which uses the full patient clinical record, here
simulated using the modeling framework. This estimator detects rapid (months)
negative changes in bone mineral density. Independently of the actual bone
mineral density, when the decrease occurs rapidly it is important to alarm the
patient and monitor him/her more closely to detect insurgence of other bone
co-morbidities. A third estimator takes into account the variance of the bone
density, which could address the investigation of metabolic syndromes, diabetes
and cancer. Our implementation could make use of different logical combinations
of these statistical estimators and could incorporate other biomarkers for
other systemic co-morbidities (for example diabetes and thalassemia). We are
delighted to report that the combination of stochastic modeling with formal
methods motivate new diagnostic framework for complex pathologies. In
particular our approach takes into consideration important properties of
biosystems such as multiscale and self-adaptiveness. The multi-diagnosis could
be further expanded, inching towards the complexity of human diseases. Finally,
we briefly introduce self-adaptiveness in formal methods which is a key
property in the regulative mechanisms of biological systems and well known in
other mathematical and engineering areas.Comment: In Proceedings CompMod 2011, arXiv:1109.104
Multiscale Bone Remodelling with Spatial P Systems
Many biological phenomena are inherently multiscale, i.e. they are
characterized by interactions involving different spatial and temporal scales
simultaneously. Though several approaches have been proposed to provide
"multilayer" models, only Complex Automata, derived from Cellular Automata,
naturally embed spatial information and realize multiscaling with
well-established inter-scale integration schemas. Spatial P systems, a variant
of P systems in which a more geometric concept of space has been added, have
several characteristics in common with Cellular Automata. We propose such a
formalism as a basis to rephrase the Complex Automata multiscaling approach
and, in this perspective, provide a 2-scale Spatial P system describing bone
remodelling. The proposed model not only results to be highly faithful and
expressive in a multiscale scenario, but also highlights the need of a deep and
formal expressiveness study involving Complex Automata, Spatial P systems and
other promising multiscale approaches, such as our shape-based one already
resulted to be highly faithful.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
- …