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Exploring the gap between dynamic and constraint-based models of metabolism
Machado, Carlos; Costa, Rafael S.; Ferreira, E. C.; Rocha, I.; Tidor, BruceSystems biology provides new approaches for metabolic engineering through the development of models and methods for simulation and optimization of microbial metabolism. Here we explore the relationship between two modeling frameworks in common use namely, dynamic models with kinetic rate laws and constraint-based flux models. We compare and analyze dynamic and constraint-based formulations of the same model of ...
Modeling formalisms in systems biology
Machado, Daniel; Costa, Rafael S.; Rocha, Miguel; Ferreira, E. C.; Tidor, Bruce; Rocha, I.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 require...
Model transformation of metabolic networks using a Petri net based framework
Machado, Daniel; Costa, Rafael S.; Rocha, Miguel; Rocha, I.; Tidor, Bruce; Ferreira, E. C.The different modeling approaches in Systems Biology create models with different levels of detail. The transformation techniques in Petri net theory can provide a solid framework for zooming between these different levels of abstraction and refinement. This work presents a Petri net based approach to Metabolic Engineering that implements model reduction methods to reduce the complexity of large-scale metabolic...
Exploring the gap between dynamic and steady-state models of metabolism
Machado, Daniel; Costa, Rafael S.; Rocha, I.; Tidor, Bruce; Ferreira, E. C.Integration of different kinds of biological networks, is within the holistic approach of Systems Biology. However, looking at metabolic networks only, one already finds a separation between dynamic [2] and steady-state [3] models of metabolism. This work reviews the differences between both modeling approaches and explores the gap between them. Common properties of both kind of models are studied in detail, us...
A critical review on modelling formalisms and simulation tools in computational...
Machado, Daniel; Costa, Rafael S.; Rocha, Miguel; Rocha, I.; Tidor, Bruce; Ferreira, E. C.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...
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