Modelling biological systems is a significant task of systems biology and mathematical biology. Computational systems biology aims to develop and use efficient

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

data structures In computer science, a data structure is a data organization, management, 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, a ...

visualization Visualization or visualisation may refer to: * Visualization (graphics), the physical or imagining creation of images, diagrams, or animations to communicate a message * Data visualization, the graphic representation of data * Information visuali ...

and communication tools with the goal of

computer modelling 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 det ...

of biological systems. It involves the use of computer simulations of biological systems, including cellular subsystems (such as the networks of metabolites and

enzyme Enzymes () are proteins that act as biological catalysts 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 products ...

s which comprise

metabolism Metabolism (, from el, μεταβολή ''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 c ...

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

biological organisation Biological organisation is the hierarchy 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 this s ...

). 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 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,

s which comprise

and

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

translation Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

, 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 Predictive modelling uses statistics to predict outcomes. Most often the event one wants to predict is in the future, but predictive modelling can be applied to any type of unknown event, regardless of when it occurred. For example, predictive mod ...

of a living cell a grand challenge for the 21st century, listed as such by the

National Science Foundation The National Science Foundation (NSF) is an independent agency of the United States government that supports fundamental research and education in all the non-medical fields of science and engineering. Its medical counterpart is the National ...

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

Mycoplasma genitalium ''Mycoplasma genitalium'' (''MG'', commonly known as Mgen) is a sexually transmitted, small and pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in humans. Medical reports published in 2007 and 2 ...

'', 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 comput ...

is the task of modelling specifically a

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

Multi-cellular organism simulation

An open source simulation of C. elegans at the cellular level is being pursued by the

OpenWorm OpenWorm is an international open science project for the purpose of simulating the roundworm ''Caenorhabditis elegans'' at the cellular level. Although the long-term goal is to model all 959 cells of the ''C. elegans'', the first stage is to mo ...

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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

from its

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha 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 may i ...

from its primary structure. It is one of the most important goals pursued by bioinformatics 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 o ...

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 secondary and tertiary structure from primary structure. Structure prediction is different ...

is of high importance in

medicine Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pr ...

(for example, in

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

) and

biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...

(for example, in the design of novel enzymes). 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 prov ...

experiment.

Human biological systems

Brain model

The

Blue Brain Project 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 ...

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 accompli ...

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 École may refer to: * an elementary school in the French educational stages normally followed by secondary education establishments (collège and lycée) * École (river), a tributary of the Seine flowing in région Île-de-France * École, Savoi ...

'' in

Lausanne , neighboring_municipalities= Bottens, Bretigny-sur-Morrens, Chavannes-près-Renens, Cheseaux-sur-Lausanne, Crissier, Cugy, Écublens, Épalinges, Évian-les-Bains (FR-74), Froideville, Jouxtens-Mézery, Le Mont-sur-Lausanne, Lugrin (FR ...

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

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

artificial neural network Artificial neural networks (ANNs), usually simply called neural networks (NNs) or neural nets, are computing systems inspired by the biological neural networks that constitute animal brains. An ANN is based on a collection of connected unit ...

, but involves a partially biologically realistic model of

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

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 sentience and awareness of internal and external existence. However, the lack of definitions has led to millennia of analyses, explanations and debates by philosophers, theologians, linguisticians, and scien ...

. 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 (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 scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...

, 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 som ...

s 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. 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 an area of knowledge that includes the topics of numbers, formulas and related structures, shapes and the spaces in which they are contained, and quantities and their changes. These topics are represented in modern mathematics ...

representations of

ecosystem An ecosystem (or ecological system) consists of all the organisms and the physical environment with which they interact. These biotic and abiotic components are linked together through nutrient cycles and energy flows. Energy enters the syste ...

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. 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 number of steps it ...

s, and quantify these as either numbers of

organism In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and ...

s, biomass or the inventory/

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 species of atoms that have a given number of protons in their nuclei, including the pure substance consisting only of that species. Unlike chemical compounds, chemical elements cannot be broken down into simpler sub ...

(for instance,

carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon mak ...

or a nutrient

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...

such as

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

phosphorus Phosphorus is a chemical element with the symbol P and atomic number 15. Elemental phosphorus exists in two major forms, white phosphorus and red phosphorus, but because it is highly reactive, phosphorus is never found as a free element on Ear ...

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, community, ecosystem, and biosphere levels. Ecotoxicology is a multidisciplinary field, which integrates toxicology and ecology ...

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 patients among a given population within an area in a short period of time. Epidemics of infectious ...

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 tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...

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