211 research outputs found
Automatic Parameterization of the Purine Metabolism Pathway through Discrete Event-based Simulation
Model development and analysis of metabolic networks is recognized as a key requirement for integrating in-vitro and in-vivo experimental data. In-silico simulation of a biochemical model allows one to test different experimental conditions, helping in the discovery of the dynamics that regulate the system. Although qualitative characterizations of such complex mechanisms are, at least partially, available, a fully-parametrized quantitative description is often miss- ing. On the other hand, several characteristics and issues to model biological systems are common to the electronics system modelling, such as concurrency, reactivity, abstraction levels, automatic reverse engineering, as well as design space explosion during validation. This work presents a methodology that applies languages, techniques, and tools well established in the context of electronic design automation (EDA) for modelling and simulation of metabolic networks through Petri nets. The paper presents the results obtained by applying the proposed methodology to model the purine metabolism starting from the metabolomics data obtained from naive lymphocytes and autoreactive T cells implicated in the induction of experimental autoimmune disorders
Efficient Simulation and Parametrization of Stochastic Petri Nets in SystemC: A Case study from Systems Biology
Stochastic Petri nets (SPN) are a form of Petri net where the transitions fire after a probabilistic and randomly determined delay. They are adopted in a wide range of appli- cations thanks to their capability of incorporating randomness in the models and taking into account possible fluctuations and environmental noise. In Systems Biology, they are becoming a reference formalism to model metabolic networks, in which the noise due to molecule interactions in the environment plays a crucial role. Some frameworks have been proposed to implement and dynamically simulate SPN. Nevertheless, they do not allow for automatic model parametrization, which is a crucial task to identify the network configurations that lead the model to satisfy temporal properties of the model. This paper presents a framework that synthesizes the SPN models into SystemC code. The framework allows the user to formally define the network properties to be observed and to automatically extrapolate, thorough Assertion-based Verification (ABV), the parameter configurations that lead the network to satisfy such properties. We applied the framework to implement and simulate a complex biological network, i.e., the purine metabolism, with the aim of reproducing the metabolomics data obtained in-vitro from naive lymphocytes and autoreactive T cells implicated in the induction of experimental autoimmune disorders
Computational Modeling, Formal Analysis, and Tools for Systems Biology.
As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science
A Study of the PDGF Signaling Pathway with PRISM
In this paper, we apply the probabilistic model checker PRISM to the analysis
of a biological system -- the Platelet-Derived Growth Factor (PDGF) signaling
pathway, demonstrating in detail how this pathway can be analyzed in PRISM. We
show that quantitative verification can yield a better understanding of the
PDGF signaling pathway.Comment: In Proceedings CompMod 2011, arXiv:1109.104
Petri Net modelling approach for analysing the behaviour of Wnt/[inline-formula removed] -catenin and Wnt/Ca 2+ signalling pathways in arrhythmogenic right ventricular cardiomyopathy.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure and sudden death. The hallmark pathological findings are progressive myocyte loss and fibro fatty replacement, with a predilection for the right ventricle. This study focuses on the adipose tissue formation in cardiomyocyte by considering the signal transduction pathways including Wnt/[inline-formula removed]-catenin and Wnt/Ca2+ regulation system. These pathways are modelled and analysed using stochastic petri nets (SPN) in order to increase our comprehension of ARVC and in turn its treatment regimen. The Wnt/[inline-formula removed]-catenin model predicts that the dysregulation or absence of Wnt signalling, inhibition of dishevelled and elevation of glycogen synthase kinase 3 along with casein kinase I are key cytotoxic events resulting in apoptosis. Moreover, the Wnt/Ca2+ SPN model demonstrates that the Bcl2 gene inhibited by c-Jun N-terminal kinase protein in the event of endoplasmic reticulum stress due to action potential and increased amount of intracellular Ca2+ which recovers the Ca2+homeostasis by phospholipase C, this event positively regulates the Bcl2 to suppress the mitochondrial apoptosis which causes ARVC
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 Integrated Qualitative and Quantitative Biochemical Model Learning Framework Using Evolutionary Strategy and Simulated Annealing
The authors would like to thank the support on this research by the CRISP Project (Combinatorial Responses In Stress Pathways) funded by the BBSRC (BB/F00513X/1) under the Systems Approaches to Biological Research (SABR) Initiative.Peer reviewedPublisher PD
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