Cellular model
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A cellular model is a
Developing such models has been a task of
Overview
The eukaryotic cell cycle is very complex and is one of the most studied topics, since its misregulation leads to cancers. It is possibly a good example of a mathematical model as it deals with simple calculus but gives valid results. Two research groups[1][2] have produced several models of the cell cycle simulating several organisms. They have recently produced a generic eukaryotic cell cycle model which can represent a particular eukaryote depending on the values of the parameters, demonstrating that the idiosyncrasies of the individual cell cycles are due to different protein concentrations and affinities, while the underlying mechanisms are conserved (Csikasz-Nagy et al., 2006).
By means of a system of ordinary differential equations these models show the change in time (dynamical system) of the protein inside a single typical cell; this type of model is called a deterministic process (whereas a model describing a statistical distribution of protein concentrations in a population of cells is called a stochastic process).
To obtain these equations an iterative series of steps must be done: first the several models and observations are combined to form a consensus diagram and the appropriate kinetic laws are chosen to write the differential equations, such as
In order to fit the parameters the differential equations need to be studied. This can be done either by simulation or by analysis.
In a simulation, given a starting
In analysis, the properties of the equations are used to investigate the behavior of the system depending on the values of the parameters and variables. A system of differential equations can be represented as a vector field, where each vector described the change (in concentration of two or more protein) determining where and how fast the trajectory (simulation) is heading. Vector fields can have several special points: a stable point, called a sink, that attracts in all directions (forcing the concentrations to be at a certain value), an unstable point, either a source or a saddle point which repels (forcing the concentrations to change away from a certain value), and a limit cycle, a closed trajectory towards which several trajectories spiral towards (making the concentrations oscillate).
A better representation which can handle the large number of variables and parameters is called a
Molecular level simulations
Cell Collective[3] is a modeling software that enables one to house dynamical biological data, build computational models, stimulate, break and recreate models. The development is led by Tomas Helikar,[4] a researcher within the field of computational biology. It is designed for biologists, students learning about computational biology, teachers focused on teaching life sciences, and researchers within the field of life science. The complexities of math and computer science are built into the backend and one can learn about the methods used for modeling biological species, but complex math equations, algorithms, programming are not required and hence won't impede model building.
The mathematical framework behind Cell Collective is based on a common qualitative (discrete) modeling technique where the regulatory mechanism of each node is described with a logical function [for more comprehensive information on logical modeling, see [5][6]].
In the July 2012 issue of Cell, a team led by Markus Covert at Stanford published the most complete computational model of a cell to date. The model of the roughly 500-gene Mycoplasma genitalium contains 28 algorithmically-independent components incorporating work from over 900 sources. It accounts for interactions of the complete genome, transcriptome, proteome, and metabolome of the organism, marking a significant advancement for the field.[7][8]
Most attempts at modeling cell cycle processes have focused on the broad, complicated molecular interactions of many different chemicals, including several
Projects
Multiple projects are in progress.[10]
- CytoSolve - Commercial platform, possibly using MATLAB
- Synthecell - Experimental group
- Karyote - Indiana University - No longer active
- E-Cell Project - Last updated 2020
- Virtual Cell - University of Connecticut Health Center- Simulation platform rather than a build a cell project
- Silicon Cell - No longer active
- WholeCell - Stanford University - No longer active
- MCell - National Center for Multiscale Modeling of Biological Systems (MMBioS) - Active as of 2023
See also
- Biological data visualization
- Biological Applications of Bifurcation Theory
- Molecular modeling software
- Membrane computing is the task of modeling specifically a cell membrane.
- Biochemical Switches in the Cell Cycle
- Masaru Tomita
References
- ^ "The JJ Tyson Lab". Virginia Tech. Retrieved 2011-07-20.
- ^ "The Molecular Network Dynamics Research Group". Budapest University of Technology and Economics. Archived from the original on 2019-10-30. Retrieved 2011-07-20.
- ^ "Interactive Modeling of Biological Networks".
- ^ "Helikar Lab - Members". Archived from the original on 2019-10-19. Retrieved 2016-02-15.
- ^ Morris MK, Saez-Rodriguez J, Sorger PK, Lauffenburger DA.. Logic-based models for the analysis of cell signaling networks. Biochemistry (2010) 49(15):3216–24.10.1021/bi902202q
- ^ Helikar T, Kowal B, Madrahimov A, Shrestha M, Pedersen J, Limbu K, et al. Bio-Logic Builder: a nontechnical tool for building dynamical, qualitative models. PLoS One (2012) 7(10):e46417.10.1371/journal.pone.0046417
- ^ http://covertlab.stanford.edu/publicationpdfs/mgenitalium_whole_cell_2012_07_20.pdf[permanent dead link]
- ^ "Stanford researchers produce first complete computer model of an organism". 2012-07-19.
- PMID 25658582.
- S2CID 10737442.