28,973 research outputs found
A Process Algebraical Approach to Modelling Compartmentalized Biological Systems
This paper introduces Protein Calculus, a special modeling language designed for encoding and calculating the behaviors of compartmentilized biological systems. The formalism combines, in a unified framework, two successful computational paradigms - process algebras and membrane systems. The goal of Protein Calculus is to provide a formal tool for transforming collected information from in vivo experiments into coded definition of the different types of proteins, complexes of proteins, and membrane-organized systems of such entities. Using this encoded information as input, our calculus computes, in silico, the possible behaviors of a living system. This is the preliminary version of a paper that was published in Proceedings of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2: 642-646, 2007 (http://scitation.aip.org/dbt/dbt.jsp?KEY=APCPCS&Volume=963&Issue=2)
Modelling Cell Cycle using Different Levels of Representation
Understanding the behaviour of biological systems requires a complex setting
of in vitro and in vivo experiments, which attracts high costs in terms of time
and resources. The use of mathematical models allows researchers to perform
computerised simulations of biological systems, which are called in silico
experiments, to attain important insights and predictions about the system
behaviour with a considerably lower cost. Computer visualisation is an
important part of this approach, since it provides a realistic representation
of the system behaviour. We define a formal methodology to model biological
systems using different levels of representation: a purely formal
representation, which we call molecular level, models the biochemical dynamics
of the system; visualisation-oriented representations, which we call visual
levels, provide views of the biological system at a higher level of
organisation and are equipped with the necessary spatial information to
generate the appropriate visualisation. We choose Spatial CLS, a formal
language belonging to the class of Calculi of Looping Sequences, as the
formalism for modelling all representation levels. We illustrate our approach
using the budding yeast cell cycle as a case study
A multiscale model for collagen alignment in wound healing
It is thought that collagen alignment plays a significant part in scar tissue formation during dermal wound healing. We present a multiscale model for collagen deposition and alignment during this process. We consider fibroblasts as discrete units moving within an extracellular matrix of collagen and fibrin modelled as continua. Our model includes flux induced alignment of collagen by fibroblasts, and contact guidance of fibroblasts by collagen fibres. We can use the model to predict the effects of certain manipulations, such as varying fibroblast speed, or placing an aligned piece of tissue in the wound. We also simulate experiments which alter the TGF-β concentrations in a healing dermal wound and use the model to offer an explanation of the observed influence of this growth factor on scarring
Cancer modelling: Getting to the heart of the problem
Paradoxically, improvements in healthcare that have enhanced the life expectancy of humans in the Western world have, indirectly, increased the prevalence of certain types of cancer such as prostate and breast. It remains unclear whether this phenomenon should be attributed to the ageing process itself or the cumulative effect of prolonged exposure to harmful environmental stimuli such as ultraviolet light, radiation and carcinogens (Franks and Teich, 1988). Equally, there is also compelling evidence that certain genetic abnormalities can predispose individuals to specific cancers (Ilyas et al., 1999). The variety of factors that have been implicated in the development of solid tumours stems, to a large extent, from the fact that ‘cancer’ is a generic term, often used to characterize a series of disorders that share common features. At this generic level of description, cancer may be viewed as a cellular disease in which controls that usually regulate growth and maintain homeostasis are disrupted. Cancer is typically initiated by genetic mutations that lead to enhanced mitosis of a cell lineage and the formation of an avascular tumour. Since it receives nutrients by diffusion from the surrounding tissue, the size of an avascular tumour is limited to several millimeters in diameter. Further growth relies on the tumour acquiring the ability to stimulate the ingrowth of a new, circulating blood supply from the host vasculature via a process termed angiogenesis (Folkman, 1974). Once vascularised, the tumour has access to a vast nutrient source and rapid growth ensues. Further, tumour fragments that break away from the primary tumour, on entering the vasculature, may be transported to other organs in which they may establish secondary tumours or metastases that further compromise the host. Invasion is another key feature of solid tumours whereby contact with the tissue stimulates the production of enzymes that digest the tissue, liberating space into which the tumour cells migrate. Thus, cancer is a complex, multiscale process. The spatial scales of interest range from the subcellular level, to the cellular and macroscopic (or tissue) levels while the timescales may vary from seconds (or less) for signal transduction pathways to months for tumour doubling times The variety of phenomena involved, the range of spatial and temporal scales over which they act and the complex way in which they are inter-related mean that the development of realistic theoretical models of solid tumour growth is extremely challenging. While there is now a large literature focused on modelling solid tumour growth (for a review, see, for example, Preziosi, 2003), existing models typically focus on a single spatial scale and, as a result, are unable to address the fundamental problem of how phenomena at different scales are coupled or to combine, in a systematic manner, data from the various scales. In this article, a theoretical framework will be presented that is capable of integrating a hierarchy of processes occurring at different scales into a detailed model of solid tumour growth (Alarcon et al., 2004). The model is formulated as a hybrid cellular automaton and contains interlinked elements that describe processes at each spatial scale: progress through the cell cycle and the production of proteins that stimulate angiogenesis are accounted for at the subcellular level; cell-cell interactions are treated at the cellular level; and, at the tissue scale, attention focuses on the vascular network whose structure adapts in response to blood flow and angiogenic factors produced at the subcellular level. Further coupling between the different spatial scales arises from the transport of blood-borne oxygen into the tissue and its uptake at the cellular level. Model simulations will be presented to illustrate the effect that spatial heterogeneity induced by blood flow through the vascular network has on the tumour’s growth dynamics and explain how the model may be used to compare the efficacy of different anti-cancer treatment protocols
Modelling of Multi-Agent Systems: Experiences with Membrane Computing and Future Challenges
Formal modelling of Multi-Agent Systems (MAS) is a challenging task due to
high complexity, interaction, parallelism and continuous change of roles and
organisation between agents. In this paper we record our research experience on
formal modelling of MAS. We review our research throughout the last decade, by
describing the problems we have encountered and the decisions we have made
towards resolving them and providing solutions. Much of this work involved
membrane computing and classes of P Systems, such as Tissue and Population P
Systems, targeted to the modelling of MAS whose dynamic structure is a
prominent characteristic. More particularly, social insects (such as colonies
of ants, bees, etc.), biology inspired swarms and systems with emergent
behaviour are indicative examples for which we developed formal MAS models.
Here, we aim to review our work and disseminate our findings to fellow
researchers who might face similar challenges and, furthermore, to discuss
important issues for advancing research on the application of membrane
computing in MAS modelling.Comment: In Proceedings AMCA-POP 2010, arXiv:1008.314
Stochastic Calculus of Wrapped Compartments
The Calculus of Wrapped Compartments (CWC) is a variant of the Calculus of
Looping Sequences (CLS). While keeping the same expressiveness, CWC strongly
simplifies the development of automatic tools for the analysis of biological
systems. The main simplification consists in the removal of the sequencing
operator, thus lightening the formal treatment of the patterns to be matched in
a term (whose complexity in CLS is strongly affected by the variables matching
in the sequences).
We define a stochastic semantics for this new calculus. As an application we
model the interaction between macrophages and apoptotic neutrophils and a
mechanism of gene regulation in E.Coli
Qualitative modelling and analysis of regulations in multi-cellular systems using Petri nets and topological collections
In this paper, we aim at modelling and analyzing the regulation processes in
multi-cellular biological systems, in particular tissues.
The modelling framework is based on interconnected logical regulatory
networks a la Rene Thomas equipped with information about their spatial
relationships. The semantics of such models is expressed through colored Petri
nets to implement regulation rules, combined with topological collections to
implement the spatial information.
Some constraints are put on the the representation of spatial information in
order to preserve the possibility of an enumerative and exhaustive state space
exploration.
This paper presents the modelling framework, its semantics, as well as a
prototype implementation that allowed preliminary experimentation on some
applications.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
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