15,918 research outputs found
An Intuitive Automated Modelling Interface for Systems Biology
We introduce a natural language interface for building stochastic pi calculus
models of biological systems. In this language, complex constructs describing
biochemical events are built from basic primitives of association, dissociation
and transformation. This language thus allows us to model biochemical systems
modularly by describing their dynamics in a narrative-style language, while
making amendments, refinements and extensions on the models easy. We
demonstrate the language on a model of Fc-gamma receptor phosphorylation during
phagocytosis. We provide a tool implementation of the translation into a
stochastic pi calculus language, Microsoft Research's SPiM
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
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
Agents in Bioinformatics
The scope of the Technical Forum Group (TFG) on Agents in Bioinformatics (BIOAGENTS) was to inspire collaboration between the agent and bioinformatics communities with the aim of creating an opportunity to propose a different (agent-based) approach to the development of computational frameworks both for data analysis in bioinformatics and for system modelling in computational biology. During the day, the participants examined the future of research on agents in bioinformatics primarily through 12 invited talks selected to cover the most relevant topics. From the discussions, it became clear that there are many perspectives to the field, ranging from bio-conceptual languages for agent-based simulation, to the definition of bio-ontology-based declarative languages for use by information agents, and to the use of Grid agents, each of which requires further exploration. The interactions between participants encouraged the development of applications that describe a way of creating agent-based simulation models of biological systems, starting from an hypothesis and inferring new knowledge (or relations) by mining and analysing the huge amount of public biological data. In this report we summarise and reflect on the presentations and discussions
Computational Modeling for the Activation Cycle of G-proteins by G-protein-coupled Receptors
In this paper, we survey five different computational modeling methods. For
comparison, we use the activation cycle of G-proteins that regulate cellular
signaling events downstream of G-protein-coupled receptors (GPCRs) as a driving
example. Starting from an existing Ordinary Differential Equations (ODEs)
model, we implement the G-protein cycle in the stochastic Pi-calculus using
SPiM, as Petri-nets using Cell Illustrator, in the Kappa Language using
Cellucidate, and in Bio-PEPA using the Bio-PEPA eclipse plug in. We also
provide a high-level notation to abstract away from communication primitives
that may be unfamiliar to the average biologist, and we show how to translate
high-level programs into stochastic Pi-calculus processes and chemical
reactions.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
- …