SmartCell

Category Cross-Omics>Agent-Based Modeling/Simulation/Tools

Abstract SmartCell is a general framework for modeling and simulation of diffusion-reaction networks in a whole-cell context.

It supports localization and diffusion by using a mesoscopic stochastic reaction model.

The SmartCell package can handle any cell geometry, considers different cell compartments, allows localization of species, supports DNA transcription and translation, membrane diffusion and multi-step reactions, as well as cell growth.

Moreover, different temporal and spatial constraints can be applied to the model. A GUI interface that facilitates model making is also available.

1) SmartCell - Model handling --

SmartCell is an object-oriented platform written in C++. As a model description language, it uses XML and complies with systems biology markup language (SBML) specifications.

The modeler can avoid the tedious task of creating the input file by using the Graphical User Interface (GUI). SmartCell parses this high-level description format into an internal format - the core model - that is subsequently used by the simulation engine.

2) SmartCell - Describing the molecular entities participating in the stochastic processes --

Molecular species in the model are referred to as entities, each with a unique name.

Entities take part in chemical processes, either as reactants (consumed in the process), products (produced) or effectors (affecting the process without being consumed - like enzymes and transcription factors).

Each entity can be declared either as species, complex or DNA.

Species are the basic type and can be assembled into complexes, while DNA entities are localized, have features like interaction sites and enable particular processes such as transcription.

3) SmartCell - Describing processes --

Processes, described in the process element, make things happen in the cell.

A process element always involves at least one entity, whose multiplicity (number of particles of that entity taking part in the process) must be specified. Multi-step processes can be declared by the Multi-step-process element.

SmartCell can handle reactions with an arbitrary number of reactants and stoichiometry. Reactions with three or more reactants, however, are more conveniently processed if they are decomposed into a set of bimolecular reactions.

A special feature of SmartCell is that the processes can occur at specific locations, as declared in the process-site element. A number of predefined regions are available, such as cytoplasm, membrane, and extra-cellular media.

4) SmartCell - Output --

The output of SmartCell is a tabulated text file containing snapshots of the cell at selected time intervals.

Each snapshot contains the (X, Y, Z) coordinates of the volumes making up the cell, with their respective distribution of species. These tables can then be loaded and displayed as animation movies or graphs.

5) SmartCell - Cell geometry, diffusion and crowding effects --

SmartCell implements a mesoscopic kinetics model in which entities are represented by their copy number and location.

Taking the spatial distribution of entities into account seems to contradict the very nature of Gillespie’s type of approach, where stochastic events operate only at the level of number of entities, without knowing where these latter are.

This obstacle is overcome by dividing the reaction volume into smaller volume elements, where stochastic events take place.

The use of a mesh allows one to consider diffusion as translocation across adjacent volume sites, as well as to handle inhomogeneities of species and processes.

The ‘geometry graph’ enables the user to describe complex features, such as the intricate transport system of the cell and membrane diffusion. Paths are used to define objects that span several sites (for example, DNA), and may have an orientation.

Vertices of dimension 2 can be used to model processes in or across membranes, while vertices of dimension 1 can be exploited to construct directed pathways between sites of any dimension, including dimension 0, which represents a single point.

The latter capability can be used, for example, to assign binding sites to the DNA entity.

The manufacturers have constructed a number of predefined regions and geometries. Solid sites for all geometries are cubic and of identical user-specified size.

A module that directly creates the cell geometry from an imported table containing coordinates, locations, regions, and species data, is also available.

SmartCell does Not handle excluded volume effects, as molecules are considered to have zero dimensions.

However, in ‘crowded environments’ such as the cell, these may be non-negligible, especially when using reaction constants that were determined for dilute solutions.

For more complex shapes and very high concentrations, where several molecules may come into close proximity, higher-order viral coefficients should be used to approximate the excluded volume effect.

At present, those corrections have to be introduced by the user.

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G6G Abstract Number 20624

G6G Manufacturer Number 104224