Multi-level dynamic modeling in biological systems : application of hybrid Petri nets to network simulation

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.This work was partially supported by post-doctoral grant by Fundacao para a Ciencia e a Tecnologia (FCT) (SFRH/BPD/80784/2011), project PneumoSyS - A Systems Biology approach to the role of pneumococcal carbon metabolism in colonization and invasive disease (FCT contract: PTDC/SAU-MII/100964/2008) and by FCT (INESC-ID multiannual funding) through the PIDDAC program funds

Petri nets for systems and synthetic biology

We give a description of a Petri net-based framework for modelling and analysing biochemical pathways, which uni¯es the qualita- tive, stochastic and continuous paradigms. Each perspective adds its con- tribution to the understanding of the system, thus the three approaches do not compete, but complement each other. We illustrate our approach by applying it to an extended model of the three stage cascade, which forms the core of the ERK signal transduction pathway. Consequently our focus is on transient behaviour analysis. We demonstrate how quali- tative descriptions are abstractions over stochastic or continuous descrip- tions, and show that the stochastic and continuous models approximate each other. Although our framework is based on Petri nets, it can be applied more widely to other formalisms which are used to model and analyse biochemical networks

Modeling formalisms in systems biology

Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future.Research supported by grants SFRH/BD/35215/2007 and SFRH/BD/25506/2005 from the Fundacao para a Ciencia e a Tecnologia (FCT) and the MIT-Portugal Program through the project "Bridging Systems and Synthetic Biology for the development of improved microbial cell factories" (MIT-Pt/BS-BB/0082/2008)

A review of modelling and verification approaches for computational biology

This paper reviews most frequently used computational modelling approaches and formal verification techniques in computational biology. The paper also compares a number of model checking tools and software suits used in analysing biological systems and biochemical networks and verifiying a wide range of biological properties

A diversity-aware computational framework for systems biology

L'abstract è presente nell'allegato / the abstract is in the attachmen

A critical review on modelling formalisms and simulation tools in computational biosystems

Integration of different kinds of biological processes is an ultimate goal for whole-cell modelling. We briefly review modelling formalisms that have been used in Systems Biology and identify the criteria that must be addressed by an integrating framework capable of modelling, analysing and simulating different biological networks. Aware that no formalism can fit all purposes we realize Petri nets as a suitable model for Metabolic Engineering and take a deeper perspective on the role of this formalism as an integrating framework for regulatory and metabolic networks.Research supported by PhD grant SFRH/BD/35215/2007 from the Fundacao para a Ciencia e a Tecnologia (FCT) and the MIT-Portugal program