Modelling biological systems is a significant task of

systems biology Systems biology is the computational modeling, computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological syst ...

and

mathematical biology Mathematical and theoretical biology, or biomathematics, is a branch of biology which employs theoretical analysis, mathematical models and abstractions of the living organisms to investigate the principles that govern the structure, development a ...

. Computational systems biology 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 simulation Computer simulation is the process of mathematical modelling, performed on a computer, which is designed to predict the behaviour of, or the outcome of, a real-world or physical system. The reliability of some mathematical models can be dete ...

s of biological systems, including cellular subsystems (such as the networks of metabolites and enzymes which comprise metabolism,

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

pathways and gene regulatory networks), to both analyze and visualize the complex connections of these cellular processes. An unexpected emergent property of a

complex system A complex system is a system composed of many components which may interact with each other. Examples of complex systems are Earth's global climate, organisms, the human brain, infrastructure such as power grid, transportation or communication ...

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) Th
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 BioModels is a free and open-source repository for storing, exchanging and retrieving quantitative models of biological interest created in 2006. All the models in the curated section of BioModels Database have been described in peer-reviewed scie ...

. Other markup languages with different emphases include

BioPAX BioPAX (Biological Pathway Exchange) is a RDF/OWL-based standard language to represent biological pathways at the molecular and cellular level. Its major use is to facilitate the exchange of pathway data. Pathway data captures our understanding of ...

and

CellML CellML is an XML based markup language for describing mathematical models. Although it could theoretically describe any mathematical model, it was originally created with the Physiome Project in mind, and hence used primarily to describe models re ...

Particular tasks

Cellular model

Creating a cellular model has been a particularly challenging task of

and

. It involves the use of

s 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. 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. 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. A dynamic computer model of intracellular signaling was the basis for Merrimack Pharmaceuticals to discover the target for their cancer medicine MM-111. 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 engin
Gepetto
has been built and models of the neural connectome and a muscle cell have been created in the NeuroML format.

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 Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthes ...

. It is one of the most important goals pursued by

bioinformatics Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...

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 Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

). 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 A supercomputer is a computer with a high level of performance as compared to a general-purpose computer. The performance of a supercomputer is commonly measured in floating-point operations per second ( FLOPS) instead of million instructions ...

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.Graham-Rowe, Duncan
"Mission to build a simulated brain begins"
''NewScientist'', June 2005. 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 The Blue Brain Project is a Swiss brain research initiative that aims to create a digital reconstruction of the mouse brain. The project was founded in May 2005 by the Brain and Mind Institute of ''École Polytechnique Fédérale de Lausanne'' (EP ...

, coordinated by the

Supercomputing and Visualization Center of Madrid The Supercomputing and Visualization Center of Madrid (CeSViMa), also called Madrid Supercomputing and Visualization Center (in Spanish, Centro de Supercomputación y Visualización de Madrid), depends on the computer science faculty of the Techn ...

(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.The Human Brain Project.
Video of Henry Markram presenting The Human Brain Project on 22 June 2012.
/ref> It is one of six pilot projects in the Future Emerging Technologies Research Program of the European Commission,
/ref> 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.

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.

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 Artificial life (often abbreviated ALife or A-Life) is a field of study wherein researchers examine systems related to natural life, its processes, and its evolution, through the use of simulations with computer models, robotics, and biochemistr ...

. A universally accepted system for describing changes in plant morphology at the cellular or modular level has yet to be devised. The most widely implemented tree generating algorithms are described in the paper
"Creation and Rendering of Realistic Trees"
an
Real-Time Tree Rendering

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 Biomass is plant-based material used as a fuel for heat or electricity production. It can be in the form of wood, wood residues, energy crops, agricultural residues, and waste from industry, farms, and households. Some people use the terms bi ...

or the

inventory Inventory (American English) or stock (British English) refers to the goods and materials that a business holds for the ultimate goal of resale, production or utilisation. Inventory management is a discipline primarily about specifying the shap ...

/ concentration of some pertinent chemical element (for instance, carbon or a

nutrient A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...

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.

Notes

References

Sources

* *
An Introduction to Infectious Disease Modelling
by Emilia Vynnycky and Richard G White. An introductory book on infectious disease modelling and its applications.

External links

The Center for Modeling Immunity to Enteric Pathogens (MIEP)
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