Modelling and simulation of signal transductions in an apoptosis pathway by using timed Petri nets

Li, Chen; Ge, Qi-Wei; Nakata, Masao; Matsuo, Hiroshi; Miyano, Satoru

doi:10.1007/s12038-007-0011-6

Cited by 48 publications

(7 citation statements)

References 25 publications

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“…The parameter identification for ODE models is in the very most cases dependent on quantitative measurements which still are a systems biology bottle neck. Another approach is the use of Petri nets [9],[10], however, the required input for parameterization is still relatively high due to the need of defining transition rules.…”

Section: Introductionmentioning

confidence: 99%

ON/OFF and Beyond - A Boolean Model of Apoptosis

et al. 2009

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Apoptosis is regulated by several signaling pathways which are extensively linked by crosstalks. Boolean or logical modeling has become a promising approach to capture the qualitative behavior of such complex networks. Here we built a large-scale literature-based Boolean model of the central intrinsic and extrinsic apoptosis pathways as well as pathways connected with them. The model responds to several external stimuli such as Fas ligand, TNF-α, UV-B irradiation, interleukin-1β and insulin. Timescales and multi-value node logic were used and turned out to be indispensable to reproduce the behavior of the apoptotic network. The coherence of the model was experimentally validated. Thereby an UV-B dose-effect is shown for the first time in mouse hepatocytes. Analysis of the model revealed a tight regulation emerging from high connectivity and spanning crosstalks and a particular importance of feedback loops. An unexpected feedback from Smac release to RIP could further increase complex II formation. The introduced Boolean model provides a comprehensive and coherent description of the apoptosis network behavior. It gives new insights into the complex interplay of pro- and antiapoptotic factors and can be easily expanded to other signaling pathways.

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Section: Introductionmentioning

confidence: 99%

ON/OFF and Beyond - A Boolean Model of Apoptosis

et al. 2009

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“…A variety of formalisms have been used to develop symbolic models of biological systems, including Petri nets [16, 17], statecharts [18], live sequence charts [19], ambient/membrane calculi [20], and rule-based systems [21, 22]. …”

Section: Symbolic Systems Biologymentioning

confidence: 99%

Epidermal Growth Factor Signaling towards Proliferation: Modeling and Logic Inference Using Forward and Backward Search

Riesco

Santos-Buitrago

Rivas

et al. 2017

BioMed Research International

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In biological systems, pathways define complex interaction networks where multiple molecular elements are involved in a series of controlled reactions producing responses to specific biomolecular signals. These biosystems are dynamic and there is a need for mathematical and computational methods able to analyze the symbolic elements and the interactions between them and produce adequate readouts of such systems. In this work, we use rewriting logic to analyze the cellular signaling of epidermal growth factor (EGF) and its cell surface receptor (EGFR) in order to induce cellular proliferation. Signaling is initiated by binding the ligand protein EGF to the membrane-bound receptor EGFR so as to trigger a reactions path which have several linked elements through the cell from the membrane till the nucleus. We present two different types of search for analyzing the EGF/proliferation system with the help of Pathway Logic tool, which provides a knowledge-based development environment to carry out the modeling of the signaling. The first one is a standard (forward) search. The second one is a novel approach based on narrowing, which allows us to trace backwards the causes of a given final state. The analysis allows the identification of critical elements that have to be activated to provoke proliferation.

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“…Petri nets are a mathematical formalism that have been applied in the modeling of several biological pathway systems (Chaouiya et al, 2004;Chen et al, 2007;Zevedei-Oancea et al, 2003). Hybrid Petri nets are a particular type of Petri net extension devel-oped to accomodate discrete and continuous elements within the same formalism.…”

Section: Introductionmentioning

confidence: 99%

MULTI-LEVEL DYNAMIC MODELING IN BIOLOGICAL SYSTEMS - Application of Hybrid Petri Nets to Network Simulation

Costa

Machado

Neves

et al. 2012

Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms

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The recent progress in the high-throughput experimental technologies allows the reconstruction of many biological networks and to evaluate changes in proteins, genes and metabolites levels in different conditions. On the other hand, computational models, when complemented with regulatory information, can be used to predict the phenotype of an organism under different genetic and environmental conditions. These computational methods can be used for example to identify molecular targets capable of inactivating a bacterium and to understand its virulence factors. This work proposes a hybrid metabolic-regulatory Petri net approach that is based on the combination of approximate enzyme-kinetic rate laws and Petri nets. A prototypic network model is used as a test-case to illustrate the application of these concepts in Systems Biology.

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Modelling and simulation of signal transductions in an apoptosis pathway by using timed Petri nets

Cited by 48 publications

References 25 publications

ON/OFF and Beyond - A Boolean Model of Apoptosis

ON/OFF and Beyond - A Boolean Model of Apoptosis

Epidermal Growth Factor Signaling towards Proliferation: Modeling and Logic Inference Using Forward and Backward Search

MULTI-LEVEL DYNAMIC MODELING IN BIOLOGICAL SYSTEMS - Application of Hybrid Petri Nets to Network Simulation

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