Visual Programming for Modeling and Simulation of Biomolecular Regulatory Networks

In this paper we introduce our new tool BIOSKETCHPAD that allows visual programming and modeling of biological regulatory networks. The tool allows biologists to create dynamic models of networks using a menu of icons, arrows, and pop-up menus, and translates the input model into CHARON, a modeling language for modular design of interacting multi-agent hybrid systems. Hybrid systems are systems that are characterized by continuous as well as discrete dynamics. Once a CHARON model of the underlying system is generated, we are able to exploit the various analysis capabilities of the CHARON toolkit, including simulation and reachability analysis. We illustrate the advantages of this approach using a case study concerning the regulation of bioluminescence in a marine bacterium

Process Calculi Abstractions for Biology

Several approaches have been proposed to model biological systems by means of the formal techniques and tools available in computer science. To mention just a few of them, some representations are inspired by Petri Nets theory, and some other by stochastic processes. A most recent approach consists in interpreting the living entities as terms of process calculi where the behavior of the represented systems can be inferred by applying syntax-driven rules. A comprehensive picture of the state of the art of the process calculi approach to biological modeling is still missing. This paper goes in the direction of providing such a picture by presenting a comparative survey of the process calculi that have been used and proposed to describe the behavior of living entities. This is the preliminary version of a paper that was published in Algorithmic Bioprocesses. The original publication is available at http://www.springer.com/computer/foundations/book/978-3-540-88868-

Modeling and Analyzing Biomolecular Networks

The authors argue for the need to model and analyze biological networks at molecular and cellular levels. They propose a computational toolbox for biologists. Central to their approach is the paradigm of hybrid models in which discrete events are combined with continuous differential equations to capture switching behavior

Proto-Plasm: parallel language for adaptive and scalable modelling of biosystems

This paper discusses the design goals and the first developments of Proto-Plasm, a novel computational environment to produce libraries of executable, combinable and customizable computer models of natural and synthetic biosystems, aiming to provide a supporting framework for predictive understanding of structure and behaviour through multiscale geometric modelling and multiphysics simulations. Admittedly, the Proto-Plasm platform is still in its infancy. Its computational framework—language, model library, integrated development environment and parallel engine—intends to provide patient-specific computational modelling and simulation of organs and biosystem, exploiting novel functionalities resulting from the symbolic combination of parametrized models of parts at various scales. Proto-Plasm may define the model equations, but it is currently focused on the symbolic description of model geometry and on the parallel support of simulations. Conversely, CellML and SBML could be viewed as defining the behavioural functions (the model equations) to be used within a Proto-Plasm program. Here we exemplify the basic functionalities of Proto-Plasm, by constructing a schematic heart model. We also discuss multiscale issues with reference to the geometric and physical modelling of neuromuscular junctions

Deterministic Intracellular Modeling

The United States Air Force is interested in the potential side effects at the cellular level from exposure to mission-essential chemicals. Presently, Air Force toxicology studies are conducted to help shed light in identifying potential hazards to workers. However, it takes a considerable amount of money, resources, and time to obtain and analyze experimental results from toxicology studies. The necessity for innovative methods that enable researchers to more effectively generate and analyze data is apparent

Engineering simulations for cancer systems biology

Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions

RULEBENDER: INTEGRATED MODELING, SIMULATION, AND VISUALIZATION FOR RULE-BASED INTRACELLULAR BIOCHEMISTRY

Rule-based modeling (RBM) is a powerful and increasingly popular approach to modeling cell signaling networks. However, novel visual tools are needed in order to make RBM accessible to a broad range of users, to make specification of models less error prone, and to improve workflows. We introduce RuleBender, a novel visualization system for the integrated visualization, modeling and simulation of rule-based intracellular biochemistry. We present the user requirements, visual paradigms, algorithms and design decisions behind RuleBender, with emphasis on visual global/local model exploration and integrated execution of simulations. The support of RBM creation, debugging, and interactive visualization expedites the RBM learning process and reduces model construction time; while built-in model simulation and results with multiple linked views streamline the execution and analysis of newly created models and generated networks. RuleBender has been adopted as both an educational and a research tool and is available as a free open source tool at http://www.rulebender.org. A development cycle that includes close interaction with expert users allows RuleBender to better serve the needs of the systems biology community