Modelling biological systems

Modelling biological systems is a significant task of systems biology and mathematical biology.[Notes 1] Computational systems biology[Notes 2][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.

Artificial life or virtual evolution attempts to understand evolutionary processes via the computer simulation of simple (artificial) life forms.

Overview

It is understood that an unexpected emergent property of a complex system is 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.

A monograph on this topic summarizes an extensive amount of published research in this area up to 1987,[2] including subsections in the following areas: computer modelling in biology and medicine, arterial system models, neuron models, biochemical and oscillation networks, quantum automata, quantum computers in molecular biology and genetics, cancer modelling, neural nets, genetic networks, abstract relational biology, metabolic-replication systems, category theory[3] applications in biology and medicine,[4] automata theory, cellular automata, tessellation models[5][6] and complete self-reproduction, chaotic systems in organisms, relational biology and organismic theories.[7][8] This published report also includes 390 references to peer-reviewed articles by a large number of authors.[9][10][11]

Standards

By far the most widely accepted standard format for storing and exchanging models in the field is the Systems Biology Markup Language (SBML)[12] The SBML.org website includes a guide to many important software packages used in computational systems biology. Other markup languages with different emphases include BioPAX and CellML.

Particular tasks

Cellular model

Main article: Cellular model
Part of the Cell Cycle
Summerhayes and Elton's 1923 food web of Bear Island (Arrows represent an organism being consumed by another organism).
A sample time-series of the Lotka-Volterra model. Note that the two populations exhibit cyclic behaviour.

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 and enzymes which comprise metabolism, signal transduction pathways and gene regulatory networks to both analyze and visualize the complex connections of these cellular processes.

The complex network of biochemical reaction/transport processes and 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.[13]

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.[14]

A dynamic computer model of intracellular signaling was the basis for Merrimack Pharmaceuticals to discover the target for their cancer medicine MM-111.[15]

Membrane computing is the task of modelling specifically a cell membrane.

Multi-cellular organism simulation

An open source simulation of C. elegans at the cellular level is being pursued by the OpenWorm community. So far the physics engine Gepetto has been built and models of the neural connectome and a muscle cell have been created in the NeuroML format.[16]

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 the most important goals pursued by bioinformatics and theoretical chemistry. Protein structure prediction 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 the 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.[17][18] 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.[19][20] It is one of six pilot projects in the Future Emerging Technologies Research Program of the European Commission,[21] 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.[22][23]

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.[24]

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.[25] The most widely implemented tree generating algorithms are described in the papers "Creation and Rendering of Realistic Trees", and Real-Time Tree Rendering

Ecological models

Main article: Ecosystem model

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 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

Notes

  1. ↑ some just calls it theoretical biology, dry biology, or even biomathematics
  2. ↑ Computational systems biology is a branch that strive to generate a system-level understanding by analyzing biological data using computational techniques.

References

  1. ↑ Andres Kriete, Roland Eils, Computational Systems Biology, Elsevier Academic Press, 2006.
  2. ↑ http://en.scientificcommons.org/1857371
  3. ↑ http://planetphysics.org/encyclopedia/BibliographyForCategoryTheoryAndAlgebraicTopologyApplicationsInTheoreticalPhysics.html
  4. ↑ http://planetphysics.org/encyclopedia/BibliographyForMathematicalBiophysicsAndMathematicalMedicine.html
  5. ↑ Modern Cellular Automata by Kendall Preston and M. J. B. Duff http://books.google.co.uk/books?id=l0_0q_e-u_UC&dq=cellular+automata+and+tessalation&pg=PP1&ots=ciXYCF3AYm&source=citation&sig=CtaUDhisM7MalS7rZfXvp689y-8&hl=en&sa=X&oi=book_result&resnum=12&ct=result
  6. ↑ http://mathworld.wolfram.com/DualTessellation.html
  7. ↑ Baianu, I. C. 1987, Computer Models and Automata Theory in Biology and Medicine., in M. Witten (ed.),Mathematical Models in Medicine, vol. 7., Ch.11 Pergamon Press, New York, 1513-1577. http://cogprints.org/3687/
  8. ↑ http://www.kli.ac.at/theorylab/EditedVol/W/WittenM1987a.html
  9. ↑ http://www.springerlink.com/content/w2733h7280521632/
  10. ↑ Currently available for download as an updated PDF: http://cogprints.ecs.soton.ac.uk/archive/00003718/01/COMPUTER_SIMULATIONCOMPUTABILITYBIOSYSTEMSrefnew.pdf
  11. ↑ http://planetphysics.org/encyclopedia/BibliographyForMathematicalBiophysics.html
  12. ↑ Klipp, Liebermeister, Helbig, Kowald and Schaber. (2007). "Systems biology standards—the community speaks" (2007), Nature Biotechnology 25(4):390–391.
  13. ↑ American Association for the Advancement of Science
  14. ↑ Karr, J. (2012) A Whole-Cell Computational Model Predicts Phenotype from Genotype Cell
  15. ↑ McDonagh, CF (2012) Antitumor Activity of a Novel Bispecific Antibody That Targets the ErbB2/ErbB3 Oncogenic Unit and Inhibits Heregulin-Induced Activation of ErbB3. Molecular Cancer Therapeutics
  16. ↑ http://www.openworm.org/downloads.html
  17. ↑ Graham-Rowe, Duncan. "Mission to build a simulated brain begins", NewScientist, June 2005.
  18. ↑ Palmer, Jason. Simulated brain closer to thought, BBC News.
  19. ↑ The Human Brain Project.
  20. ↑ Video of Henry Markram presenting The Human Brain Project on 22 June 2012.
  21. ↑ FET Flagships Initiative homepage.
  22. ↑
  23. ↑ "Computer Simulation Captures Immune Response To Flu". Retrieved 2009-08-19.
  24. ↑ Virtual Liver Network.
  25. ↑ "Simulating plant growth". Retrieved 2009-10-18.

Sources

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. PMID 14735121.
Covert; Schilling, C.; Palsson, B. (2001). "Regulation of gene expression in flux balance models of metabolism". Journal of Theoretical Biology 213 (1): 73–88. doi:10.1006/jtbi.2001.2405. PMID 11708855.
Covert, M. W.; Palsson, B. . (2002). "Transcriptional regulation in constraints-based metabolic models of Escherichia coli". The Journal of Biological Chemistry 277 (31): 28058–28064. doi:10.1074/jbc.M201691200. PMID 12006566.
Edwards; Palsson, B. (2000). "The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities". Proceedings of the National Academy of Sciences of the United States of America 97 (10): 5528–5533. Bibcode:2000PNAS...97.5528E. doi:10.1073/pnas.97.10.5528. PMC 25862. PMID 10805808.
Bonneau, R. (2008). "Learning biological networks: from modules to dynamics". Nature chemical biology 4 (11): 658–664. doi:10.1038/nchembio.122. PMID 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. PMID 11175725.
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. PMID 10191380.
Hartwell, L. H.; Hopfield, J. J.; Leibler, S.; Murray, A. W. (1999). "From molecular to modular cell biology". Nature 402 (6761 Suppl): C47–C52. doi:10.1038/35011540. PMID 10591225.
Ideker; Galitski, T.; Hood, L. (2001). "A new approach to decoding life: systems biology". Annual review of genomics and human genetics 2 (1): 343–372. doi:10.1146/annurev.genom.2.1.343. PMID 11701654.
Kitano, H. (2002). "Computational systems biology". Nature 420 (6912): 206–210. Bibcode:2002Natur.420..206K. doi:10.1038/nature01254. PMID 12432404.
Kitano, H. (2002). "Systems biology: a brief overview". Science 295 (5560): 1662–1664. Bibcode:2002Sci...295.1662K. doi:10.1126/science.1069492. PMID 11872829.
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/s00294-002-0285-z. PMID 12073094.
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.; Lefkowitz, R. J.; Pawson, A. J. (2002). "Overview of the Alliance for Cellular Signaling". Nature 420 (6916): 703–706. doi:10.1038/nature01304. PMID 12478301.
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. PMID 14580578.
Segrè, D.; Vitkup, D.; Church, G. M. (2002). "Analysis of optimality in natural and perturbed metabolic networks". Proceedings of the National Academy of Sciences of the United States of America 99 (23): 15112–15117. Bibcode:2002PNAS...9915112S. doi:10.1073/pnas.232349399. PMC 137552. PMID 12415116.
Wildermuth, MC (2000). "Metabolic control analysis: biological applications and insights.". Genome Biology 1 (6): REVIEWS1031. doi:10.1186/gb-2000-1-6-reviews1031. PMC 138895. PMID 11178271.

External links