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Institute
BTU
Fuzzy stochastic Petri nets for modeling biological systems with uncertain kinetic parameters
(2016)
Coloured Petri nets for multilevel, multiscale and multidimensional modelling of biological systems
(2019)
Coloured Hybrid Petri Nets: an Adaptable Modelling Approach for Multi-scale Biological Networks
(2018)
We consider coloured Petri nets, qualitative and quantitative ones alike, as supported by our PetriNuts tool family, comprising, among others, Snoopy, Marcie and Spike. Currently, most analysis and simulation techniques require to unfold the given coloured Petri net into its corresponding plain, uncoloured Petri net representation. This unfolding step is rather straightforward for finite discrete colour sets, but tends to be time-consuming due to the potentially huge number of possible transition bindings. We present an unfolding approach building on a special type of symbolic data structures, called Interval Decision Diagram, and compare its runtime performance with an unfolding engine employing an off-the-shelf library to solve constraint satisfaction problems. For this comparison we use the 22 scalable coloured models from the MCC benchmark suite, complemented by a few from our own collection.
Fuzzy Petri nets
(2021)
This document explains the procedure of modelling and simulating FPN
and FPNC in Snoopy; please compare Figure 1 . Please note that the same
steps for one net class can be equally applied to the other classes, just differentiate between uncoloured Petri nets (PN) and coloured Petri nets (PNC).
Furthermore, we give more details about Latin Hybercube Sampling strategies supported by Snoopy's FPN.
Integrated modelling of biological systems is becoming a necessity for constructing models containing the major biochemical processes of such systems in order to obtain a holistic understanding of their dynamics and to elucidate emergent behaviours. Hybrid modelling methods are crucial to achieve integrated modelling of biological systems. This paper reviews currently popular hybrid modelling methods, developed for systems biology, mainly revealing why they are proposed, how they are formed from single modelling formalisms and how to simulate them. By doing this, we identify future research requirements regarding hybrid approaches for further promoting integrated modelling of biological systems.
Whole-cell modeling aims to incorporate all main genes and processes, and their interactions of a cell in one model. Whole-cell modeling has been regarded as the central aim of systems biology but also as a grand challenge, which plays essential roles in current and future systems biology. In this paper, we analyze whole-cell modeling challenges and requirements and classify them into three aspects (or dimensions): heterogeneous biochemical networks, uncertainties in components, and representation of cell structure. We then explore how to use different Petri net classes to address different aspects of whole-cell modeling requirements. Based on these analyses, we present a Petri nets-based framework for whole-cell modeling, which not only addresses many whole-cell modeling requirements, but also offers a graphical, modular, and hierarchical modeling tool. We think this framework can offer a feasible modeling approach for whole-cell model construction.
Snoopy is a powerful modelling and simulation tool for various types of Petri nets, which have been applied to a wide range of biochemical reaction networks. We present an enhanced version of Snoopy, now supporting coloured and uncoloured stochastic, continuous and hybrid Petri Nets with fuzzy kinetic parameters. Colour helps to cope with modelling challenges imposed by larger and more complex networks. Fuzzy parameters are specifically useful when kinetic parameter values can not be precisely measured or estimated. By running fuzzy simulation we obtain output bands of the variables of interest induced by the effect of the fuzzy kinetic parameters. Simulation is always done on the uncoloured level. For this purpose, coloured fuzzy Petri nets are automatically unfolded to their corresponding uncoloured counterparts. Combining the power of fuzzy kinetic parameters with the modelling convenience of coloured Petri nets provides a new quality in user support with sophisticated modelling and analysis features.
Membrane systems are a very powerful computational modelling formalism inspired by the internal organisation of living cells. Modelling of membrane systems is challenged by composing many structurally similar components, which may result in very large models. Furthermore, some components may suffer from a lack of precise kinetic parameters. Coloured fuzzy Petri nets combine coloured Petri nets with fuzzy kinetic parameters, and thus offer an approach to address these challenges. In this paper, we use coloured fuzzy Petri nets to model and simulate membrane systems which are enriched by fuzzy kinetic parameters. We also introduce a methodology and workflow utilising coloured fuzzy Petri nets for modelling and simulating general biological systems which have to cope with incomplete knowledge of their kinetic data.
Integrated modelling of biological systems is challenged by composing components with sufficient kinetic data and components with insufficient kinetic data or components built only using experts’ experience and knowledge. Fuzzy continuous Petri nets (FCPNs) combine continuous Petri nets with fuzzy inference systems, and thus offer an hybrid uncertain/certain approach to integrated modelling of such biological systems with uncertainties. In this paper, we give a formal definition and a corresponding simulation algorithm of FCPNs, and briefly introduce the FCPN tool that we have developed for implementing FCPNs. We then present a methodology and workflow utilizing FCPNs to achieve hybrid (uncertain/certain) modelling of biological systems illustrated with a case study of the Mercaptopurine metabolic pathway. We hope this research will promote the wider application of FCPNs and address the uncertain/certain integrated modelling challenge in the systems biology area.