Modelling biological systems

Modelling biological systems is a significant task of systems biology and mathematical biology.[a]
Computational systems biology[b][1] aims to develop and use efficient algorithms, data structures,
visualization and communication tools with the goal of computer modelling of biological systems. It
involves the use of computer simulations of biological systems, including cellular subsystems (such as the
networks of metabolites and enzymes which comprise metabolism, signal transduction pathways and gene
regulatory networks), to both analyze and visualize the complex connections of these cellular processes.[2]

An unexpected emergent property of a complex system may be a result of the interplay of the cause-and-
effect among simpler, integrated parts (see biological organisation). Biological systems manifest many
important examples of emergent properties in the complex interplay of components. Traditional study of
biological systems requires reductive methods in which quantities of data are gathered by category, such as
concentration over time in response to a certain stimulus. Computers are critical to analysis and modelling
of these data. The goal is to create accurate real-time models of a system's response to environmental and
internal stimuli, such as a model of a cancer cell in order to find weaknesses in its signalling pathways, or
modelling of ion channel mutations to see effects on cardiomyocytes and in turn, the function of a beating
heart.

Standards
By far the most widely accepted standard format for storing and exchanging models in the field is the
Systems Biology Markup Language (SBML).[3] The SBML.org (http://sbml.org/) website includes a guide
to many important software packages used in computational systems biology. A large number of models
encoded in SBML can be retrieved from BioModels. Other markup languages with different emphases
include BioPAX and CellML.

Particular tasks

Cellular model

Creating a cellular model has been a particularly challenging task of

systems biology and mathematical biology. It involves the use of
computer simulations of the many cellular subsystems such as the
networks of metabolites, enzymes which comprise metabolism and
transcription, translation, regulation and induction of gene regulatory
networks.[4]

The complex network of biochemical reaction/transport processes and

Part of the cell cycle
their spatial organization make the development of a predictive model
of a living cell a grand challenge for the 21st century, listed as such by
the National Science Foundation (NSF) in 2006.[5]

A whole cell computational model for the bacterium Mycoplasma genitalium, including all its 525 genes,
gene products, and their interactions, was built by scientists from Stanford University and the J. Craig
Venter Institute and published on 20 July 2012 in Cell.[6]
A dynamic computer model of intracellular signaling was the basis for
Merrimack Pharmaceuticals to discover the target for their cancer
medicine MM-111.[7]

Membrane computing is the task of modelling specifically a cell

membrane.

Multi-cellular organism simulation

Summerhayes and Elton's 1923
An open source simulation of C. elegans at the cellular level is being food web of Bear Island (Arrows
pursued by the OpenWorm community. So far the physics engine represent an organism being
Gepetto (https://github.com/openworm/OpenWorm/wiki/Geppetto--Ov consumed by another organism).
erview) has been built and models of the neural connectome and a
muscle cell have been created in the NeuroML
format.[8]

Protein folding

Protein structure prediction is the prediction of the

three-dimensional structure of a protein from its amino
acid sequence—that is, the prediction of a protein's
tertiary structure from its primary structure. It is one of A sample time-series of the Lotka–Volterra model.
the most important goals pursued by bioinformatics Note that the two populations exhibit cyclic
and theoretical chemistry. Protein structure prediction behaviour.
is of high importance in medicine (for example, in
drug design) and biotechnology (for example, in the
design of novel enzymes). Every two years, the performance of current methods is assessed in the CASP
experiment.

Human biological systems

Brain model

The Blue Brain Project is an attempt to create a synthetic brain by reverse-engineering the mammalian brain
down to the molecular level. The aim of this project, founded in May 2005 by the Brain and Mind Institute
of the École Polytechnique in Lausanne, Switzerland, is to study the brain's architectural and functional
principles. The project is headed by the Institute's director, Henry Markram. Using a Blue Gene
supercomputer running Michael Hines's NEURON software, the simulation does not consist simply of an
artificial neural network, but involves a partially biologically realistic model of neurons.[9][10] It is hoped by
its proponents that it will eventually shed light on the nature of consciousness. There are a number of sub-
projects, including the Cajal Blue Brain, coordinated by the Supercomputing and Visualization Center of
Madrid (CeSViMa), and others run by universities and independent laboratories in the UK, U.S., and
Israel. The Human Brain Project builds on the work of the Blue Brain Project.[11][12] It is one of six pilot
projects in the Future Emerging Technologies Research Program of the European Commission,[13]
competing for a billion euro funding.

Model of the immune system

The last decade has seen the emergence of a growing number of simulations of the immune system.[14][15]

Virtual liver

The Virtual Liver project is a 43 million euro research program funded by the German Government, made
up of seventy research group distributed across Germany. The goal is to produce a virtual liver, a dynamic
mathematical model that represents human liver physiology, morphology and function.[16]

Tree model

Electronic trees (e-trees) usually use L-systems to simulate growth. L-systems are very important in the field
of complexity science and A-life. A universally accepted system for describing changes in plant
morphology at the cellular or modular level has yet to be devised.[17] The most widely implemented tree
generating algorithms are described in the papers "Creation and Rendering of Realistic Trees" (http://portal.
acm.org/citation.cfm?id=218427) and Real-Time Tree Rendering (https://doi.org/10.1007%2F978-3-540-2
5944-2_22).

Ecological models

Ecosystem models are mathematical representations of ecosystems. Typically they simplify complex
foodwebs down to their major components or trophic levels, and quantify these as either numbers of
organisms, biomass or the inventory/concentration of some pertinent chemical element (for instance, carbon
or a nutrient species such as nitrogen or phosphorus).

Models in ecotoxicology

The purpose of models in ecotoxicology is the understanding, simulation and prediction of effects caused
by toxicants in the environment. Most current models describe effects on one of many different levels of
biological organization (e.g. organisms or populations). A challenge is the development of models that
predict effects across biological scales. Ecotoxicology and models (http://www.ecotoxmodels.org/)
discusses some types of ecotoxicological models and provides links to many others.

Modelling of infectious disease

It is possible to model the progress of most infectious diseases mathematically to discover the likely
outcome of an epidemic or to help manage them by vaccination. This field tries to find parameters for
various infectious diseases and to use those parameters to make useful calculations about the effects of a
mass vaccination programme.

See also
Biological data visualization
Biosimulation
Gillespie algorithm
Molecular modelling software
 Stochastic simulation

Notes
a. Sometimes called theoretical biology, dry biology, or even biomathematics.
b. Computational systems biology is a branch that strives to generate a system-level
understanding by analyzing biological data using computational techniques.

References
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Further reading
Barab, A. -L.; Oltvai, Z. (2004). "Network biology* understanding the cell's functional
organization". Nature Reviews Genetics. 5 (2): 101–113. doi:10.1038/nrg1272 (https://doi.or
g/10.1038%2Fnrg1272). PMID 14735121 (https://pubmed.ncbi.nlm.nih.gov/14735121).
S2CID 10950726 (https://api.semanticscholar.org/CorpusID:10950726).
Covert; Schilling, C.; Palsson, B. (2001). "Regulation of gene expression in flux balance
models of metabolism". Journal of Theoretical Biology. 213 (1): 73–88.
CiteSeerX 10.1.1.110.1647 (https://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.110.
1647). doi:10.1006/jtbi.2001.2405 (https://doi.org/10.1006%2Fjtbi.2001.2405).
PMID 11708855 (https://pubmed.ncbi.nlm.nih.gov/11708855).
Covert, M. W.; Palsson, B. . (2002). "Transcriptional regulation in constraints-based
metabolic models of Escherichia coli" (https://doi.org/10.1074%2Fjbc.M201691200). The
Journal of Biological Chemistry. 277 (31): 28058–28064. doi:10.1074/jbc.M201691200 (http
s://doi.org/10.1074%2Fjbc.M201691200). PMID 12006566 (https://pubmed.ncbi.nlm.nih.gov/
12006566).
Edwards; Palsson, B. (2000). "The Escherichia coli MG1655 in silico metabolic genotype*
its definition, characteristics, and capabilities" (https://www.ncbi.nlm.nih.gov/pmc/articles/PM
C25862). Proceedings of the National Academy of Sciences of the United States of America.
97 (10): 5528–5533. Bibcode:2000PNAS...97.5528E (https://ui.adsabs.harvard.edu/abs/200
0PNAS...97.5528E). doi:10.1073/pnas.97.10.5528 (https://doi.org/10.1073%2Fpnas.97.10.5
528). PMC 25862 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC25862). PMID 10805808
(https://pubmed.ncbi.nlm.nih.gov/10805808).
Bonneau, R. (2008). "Learning biological networks* from modules to dynamics". Nature
Chemical Biology. 4 (11): 658–664. doi:10.1038/nchembio.122 (https://doi.org/10.1038%2Fn
chembio.122). PMID 18936750 (https://pubmed.ncbi.nlm.nih.gov/18936750).
Edwards, J. S.; Ibarra, R. U.; Palsson, B. O. (2001). "In silico predictions of Escherichia coli
metabolic capabilities are consistent with experimental data". Nature Biotechnology. 19 (2):
125–130. doi:10.1038/84379 (https://doi.org/10.1038%2F84379). PMID 11175725 (https://pu
bmed.ncbi.nlm.nih.gov/11175725). S2CID 1619105 (https://api.semanticscholar.org/CorpusI
D:1619105).
Fell, D. A. (1998). "Increasing the flux in metabolic pathways* A metabolic control analysis
perspective". Biotechnology and Bioengineering. 58 (2–3): 121–124.
doi:10.1002/(SICI)1097-0290(19980420)58:2/3<121::AID-BIT2>3.0.CO;2-N (https://doi.org/1
0.1002%2F%28SICI%291097-0290%2819980420%2958%3A2%2F3%3C121%3A%3AAID
-BIT2%3E3.0.CO%3B2-N). PMID 10191380 (https://pubmed.ncbi.nlm.nih.gov/10191380).
Hartwell, L. H.; Hopfield, J. J.; Leibler, S.; Murray, A. W. (1999). "From molecular to modular
cell biology" (https://doi.org/10.1038%2F35011540). Nature. 402 (6761 Suppl): C47–C52.
doi:10.1038/35011540 (https://doi.org/10.1038%2F35011540). PMID 10591225 (https://pub
med.ncbi.nlm.nih.gov/10591225). S2CID 34290973 (https://api.semanticscholar.org/CorpusI
D:34290973).
Ideker; Galitski, T.; Hood, L. (2001). "A new approach to decoding life* systems biology" (http
s://semanticscholar.org/paper/0d497f0eb4316b95686230f6c04a75cb520d6290). Annual
Review of Genomics and Human Genetics. 2 (1): 343–372.
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PMID 11701654 (https://pubmed.ncbi.nlm.nih.gov/11701654). S2CID 922378 (https://api.se
manticscholar.org/CorpusID:922378).
Kitano, H. (2002). "Computational systems biology". Nature. 420 (6912): 206–210.
Bibcode:2002Natur.420..206K (https://ui.adsabs.harvard.edu/abs/2002Natur.420..206K).
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pubmed.ncbi.nlm.nih.gov/12432404). S2CID 4401115 (https://api.semanticscholar.org/Corp
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Kitano (2002). "Looking beyond the details* a rise in system-oriented approaches in
genetics and molecular biology". Current Genetics. 41 (1): 1–10. doi:10.1007/s00294-002-
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bi.nlm.nih.gov/12073094). S2CID 18976498 (https://api.semanticscholar.org/CorpusID:1897
6498).
Gilman, A. G.; Simon, M. I.; Bourne, H. R.; Harris, B. A.; Long, R.; Ross, E. M.; Stull, J. T.;
Taussig, R.; Bourne, H. R.; Arkin, A. P.; Cobb, M. H.; Cyster, J. G.; Devreotes, P. N.; Ferrell, J.
E.; Fruman, D.; Gold, M.; Weiss, A.; Stull, J. T.; Berridge, M. J.; Cantley, L. C.; Catterall, W. A.;
Coughlin, S. R.; Olson, E. N.; Smith, T. F.; Brugge, J. S.; Botstein, D.; Dixon, J. E.; Hunter, T.;
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s://deepblue.lib.umich.edu/bitstream/2027.42/62977/1/nature01304.pdf) (PDF). Nature. 420
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Palsson, Bernhard (2006). Systems biology* properties of reconstructed networks.
Cambridge: Cambridge University Press. ISBN 978-0-521-85903-5.
Kauffman; Prakash, P.; Edwards, J. S. (2003). "Advances in flux balance analysis". Current
Opinion in Biotechnology. 14 (5): 491–496. doi:10.1016/j.copbio.2003.08.001 (https://doi.or
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Segrè, D.; Vitkup, D.; Church, G. M. (2002). "Analysis of optimality in natural and perturbed
metabolic networks" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC137552). Proceedings
of the National Academy of Sciences of the United States of America. 99 (23): 15112–15117.
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S). doi:10.1073/pnas.232349399 (https://doi.org/10.1073%2Fpnas.232349399).
PMC 137552 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC137552). PMID 12415116 (http
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Wildermuth, MC (2000). "Metabolic control analysis* biological applications and insights" (ht
tps://www.ncbi.nlm.nih.gov/pmc/articles/PMC138895). Genome Biology. 1 (6):
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PMID 11178271 (https://pubmed.ncbi.nlm.nih.gov/11178271).

External links
The Center for Modeling Immunity to Enteric Pathogens (MIEP) (http://www.modelingimmuni
ty.org/)

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