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 system ...

and

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

. Computational systems biology aims to develop and use efficient

algorithms In mathematics and computer science, an algorithm () is a finite sequence of mathematically rigorous instructions, typically used to solve a class of specific problems or to perform a computation. Algorithms are used as specifications for per ...

data structures In computer science, a data structure is a data organization and storage format that is usually chosen for efficient access to data. More precisely, a data structure is a collection of data values, the relationships among them, and the functi ...

, visualization and communication tools with the goal of

computer modelling Computer simulation is the running of a mathematical model on a computer, the model being designed to represent the behaviour of, or the outcome of, a real-world or physical system. The reliability of some mathematical models can be determin ...

of biological systems. It involves the use of

computer simulation Computer simulation is the running of a mathematical model on a computer, the model being designed to represent the behaviour of, or the outcome of, a real-world or physical system. The reliability of some mathematical models can be determin ...

s of biological systems, including cellular subsystems (such as the networks of metabolites and

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s which comprise

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

pathways and

gene regulatory network A gene (or genetic) regulatory network (GRN) is a collection of molecular regulators that interact with each other and with other substances in the cell to govern the gene expression levels of mRNA and proteins which, in turn, determine the fu ...

s), 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 that may interact with one another. Examples of complex systems are Earth's global climate, organisms, the human brain, infrastructure such as power grid, transportation or communication sy ...

may be a result of the interplay of the cause-and-effect among simpler, integrated parts (see

biological organisation Biological organization is the organization of complex biological structures and systems that define life using a reductionistic approach. The traditional hierarchy, as detailed below, extends from atoms to biospheres. The higher levels of t ...

). 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. Other markup languages with different emphases include BioPAX, CellML an
MorpheusML

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,

s which comprise

and transcription,

translation Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...

, 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 The U.S. National Science Foundation (NSF) is an Independent agencies of the United States government#Examples of independent agencies, independent agency of the Federal government of the United States, United States federal government that su ...

(NSF) in 2006. A whole cell computational model for the bacterium ''

Mycoplasma genitalium ''Mycoplasma genitalium'' (also known as ''MG','' Mgen, or since 2018, ''Mycoplasmoides genitalium'') is a sexually transmitted, small and pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in ...

'', 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 Membrane computing (or MC) is an area within computer science that seeks to discover new computational models from the study of biological cells, particularly of the cellular membranes. It is a sub-task of creating a cellular model. Membrane comp ...

is the task of modelling specifically a

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

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 Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

from its

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

sequence—that is, the prediction of a protein's

tertiary structure Protein tertiary structure is the three-dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains and the ...

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 biosynthe ...

. It is one of the most important goals pursued by

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

and

theoretical chemistry Theoretical chemistry is the branch of chemistry which develops theoretical generalizations that are part of the theoretical arsenal of modern chemistry: for example, the concepts of chemical bonding, chemical reaction, valence, the surface ...

Protein structure prediction Protein structure prediction is the inference of the three-dimensional structure of a protein from its amino acid sequence—that is, the prediction of its Protein secondary structure, secondary and Protein tertiary structure, tertiary structure ...

is of high importance in

medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...

(for example, in

drug design Drug design, often referred to as rational drug design or simply rational design, is the invention, inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic compound, organi ...

) and

biotechnology Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...

(for example, in the design of novel

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

). Every two years, the performance of current methods is assessed in the

CASP Critical Assessment of Structure Prediction (CASP), sometimes called Critical Assessment of Protein Structure Prediction, is a community-wide, worldwide experiment for protein structure prediction taking place every two years since 1994. CASP pro ...

experiment.

Human biological systems

Brain model

The Blue Brain Project is an attempt to create a synthetic brain by

reverse-engineering Reverse engineering (also known as backwards engineering or back engineering) is a process or method through which one attempts to understand through deductive reasoning how a previously made device, process, system, or piece of software accompl ...

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 (, ; also known as Polytechnique or l'X ) is a ''grande école'' located in Palaiseau, France. It specializes in science and engineering and is a founding member of the Polytechnic Institute of Paris. The school was founded in 1794 by mat ...

'' in

Lausanne Lausanne ( , ; ; ) is the capital and largest List of towns in Switzerland, city of the Swiss French-speaking Cantons of Switzerland, canton of Vaud, in Switzerland. It is a hilly city situated on the shores of Lake Geneva, about halfway bet ...

, 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 Blue Gene was an IBM project aimed at designing supercomputers that can reach operating speeds in the petaFLOPS (PFLOPS) range, with relatively low power consumption. The project created three generations of supercomputers, Blue Gene/L, Blue ...

supercomputer A supercomputer is a type of 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 instruc ...

running Michael Hines's NEURON software, the simulation does not consist simply of an

artificial neural network In machine learning, a neural network (also artificial neural network or neural net, abbreviated ANN or NN) is a computational model inspired by the structure and functions of biological neural networks. A neural network consists of connected ...

, but involves a partially biologically realistic model of

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s.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 Consciousness, at its simplest, is awareness of a state or object, either internal to oneself or in one's external environment. However, its nature has led to millennia of analyses, explanations, and debate among philosophers, scientists, an ...

. 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.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 Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...

, morphology and function.

Tree model

Electronic trees (e-trees) usually use

L-system An L-system or Lindenmayer system is a parallel rewriting system and a type of formal grammar. An L-system consists of an alphabet of symbols that can be used to make strings, a collection of production rules that expand each symbol into some ...

s to simulate growth. L-systems are very important in the field of

complexity science A complex system is a system composed of many components that may interact with one another. Examples of complex systems are Earth's global climate, organisms, the human brain, infrastructure such as power grid, transportation or communication sy ...

and A-life. 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 Mathematics is a field of study that discovers and organizes methods, Mathematical theory, theories and theorems that are developed and Mathematical proof, proved for the needs of empirical sciences and mathematics itself. There are many ar ...

representations of

ecosystem An ecosystem (or ecological system) is a system formed by Organism, organisms in interaction with their Biophysical environment, environment. The Biotic material, biotic and abiotic components are linked together through nutrient cycles and en ...

s. Typically they simplify complex foodwebs down to their major components or

trophic level The trophic level of an organism is the position it occupies in a food web. Within a food web, a food chain is a succession of organisms that eat other organisms and may, in turn, be eaten themselves. The trophic level of an organism is the ...

s, and quantify these as either numbers of

organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...

biomass Biomass is a term used in several contexts: in the context of ecology it means living organisms, and in the context of bioenergy it means matter from recently living (but now dead) organisms. In the latter context, there are variations in how ...

or the

inventory Inventory (British English) or stock (American English) is a quantity of 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 ...

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

of some pertinent

chemical element A chemical element is a chemical substance whose atoms all have the same number of protons. The number of protons is called the atomic number of that element. For example, oxygen has an atomic number of 8: each oxygen atom has 8 protons in its ...

(for instance,

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

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 A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...

such as

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

phosphorus Phosphorus is a chemical element; it has Chemical symbol, symbol P and atomic number 15. All elemental forms of phosphorus are highly Reactivity (chemistry), reactive and are therefore never found in nature. They can nevertheless be prepared ar ...

Models in ecotoxicology

The purpose of models in

ecotoxicology Ecotoxicology is the study of the effects of toxic chemicals on biological organisms, especially at the population biology, population, biological community, community, ecosystem, and biosphere levels. Ecotoxicology is a multidisciplinary field, ...

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 An epidemic (from Greek ἐπί ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of hosts in a given population within a short period of time. For example, in meningococcal infection ...

or to help manage them by

vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...

. This field tries to find

parameter A parameter (), generally, is any characteristic that can help in defining or classifying a particular system (meaning an event, project, object, situation, etc.). That is, a parameter is an element of a system that is useful, or critical, when ...

s for various

infectious disease An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

s and to use those parameters to make useful calculations about the effects of a mass

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)
{{Computational science Bioinformatics Biosimulation Computational science Mathematical and theoretical biology Mathematical modeling Systems biology Systems theory