Systems biology
Encyclopedia
Biological system
In biology, a biological system is a group of organs that work together to perform a certain task. Common systems, such as those present in mammals and other animals, seen in human anatomy, are those such as the circulatory system, the respiratory system, the nervous system, etc.A group of systems...
s, claiming that it uses a new perspective (holism
Holism
Holism is the idea that all the properties of a given system cannot be determined or explained by its component parts alone...
instead of reduction). Particularly from year 2000 onwards, the term is used widely in the biosciences, and in a variety of contexts. An often stated ambition of systems biology is the modeling and discovery of emergent properties, properties of a system whose theoretical description is only possible using techniques which fall under the remit of systems biology. These typically involve cell signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
networks, via long-range allostery.
Overview
Systems biology can be considered from a number of different aspects:- As a field of study, particularly, the study of the interactions between the components of biological systems, and how these interactions give rise to the function and behavior of that system (for example, the enzymes and metabolites in a metabolic pathwayMetabolic pathwayIn biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
).
- As a paradigmParadigmThe word paradigm has been used in science to describe distinct concepts. It comes from Greek "παράδειγμα" , "pattern, example, sample" from the verb "παραδείκνυμι" , "exhibit, represent, expose" and that from "παρά" , "beside, beyond" + "δείκνυμι" , "to show, to point out".The original Greek...
, usually defined in antithesis to the so-called reductionist paradigm (biological organisation), although fully consistent with the scientific methodScientific methodScientific method refers to a body of techniques for investigating phenomena, acquiring new knowledge, or correcting and integrating previous knowledge. To be termed scientific, a method of inquiry must be based on gathering empirical and measurable evidence subject to specific principles of...
. The distinction between the two paradigms is referred to in these quotations:
- "The reductionist approach has successfully identified most of the components and many of the interactions but, unfortunately, offers no convincing concepts or methods to understand how system properties emerge...the pluralism of causes and effects in biological networks is better addressed by observing, through quantitative measures, multiple components simultaneously and by rigorous data integration with mathematical models" Sauer et al
- "Systems biology...is about putting together rather than taking apart, integration rather than reduction. It requires that we develop ways of thinking about integration that are as rigorous as our reductionist programmes, but different....It means changing our philosophy, in the full sense of the term" Denis NobleDenis NobleDenis Noble CBE FRS FRCP is a British biologist who held the Burdon Sanderson Chair of Cardiovascular Physiology at Oxford University from 1984 to 2004 and was appointed Professor Emeritus and co-Director of Computational Physiology. He is one of the pioneers of Systems Biology and developed the...
- As a series of operational protocols used for performing research, namely a cycle composed of theory, analytic or computational modelling to propose specific testable hypotheses about a biological system, experimental validation, and then using the newly acquired quantitative description of cells or cell processes to refine the computational model or theory. Since the objective is a model of the interactions in a system, the experimental techniques that most suit systems biology are those that are system-wide and attempt to be as complete as possible. Therefore, transcriptomics, metabolomicsMetabolomicsMetabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles...
, proteomicsProteomicsProteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
and high-throughput techniques are used to collect quantitative data for the construction and validation of models.
- As the application of dynamical systems theoryDynamical systems theoryDynamical systems theory is an area of applied mathematics used to describe the behavior of complex dynamical systems, usually by employing differential equations or difference equations. When differential equations are employed, the theory is called continuous dynamical systems. When difference...
to molecular biologyMolecular biologyMolecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
.
- As a socioscientific phenomenon defined by the strategy of pursuing integration of complex data about the interactions in biological systems from diverse experimental sources using interdisciplinary tools and personnel.
This variety of viewpoints is illustrative of the fact that systems biology refers to a cluster of peripherally overlapping concepts rather than a single well-delineated field. However the term has widespread currency and popularity as of 2007, with chairs and institutes of systems biology proliferating worldwide.
History
Systems biology finds its roots in:- the quantitative modeling of enzyme kineticsEnzyme kineticsEnzyme kinetics is the study of the chemical reactions that are catalysed by enzymes. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction investigated...
, a discipline that flourished between 1900 and 1970, - the mathematical modeling of population growth,
- the simulations developed to study neurophysiology, and
- control theoryControl theoryControl theory is an interdisciplinary branch of engineering and mathematics that deals with the behavior of dynamical systems. The desired output of a system is called the reference...
and cyberneticsCyberneticsCybernetics is the interdisciplinary study of the structure of regulatory systems. Cybernetics is closely related to information theory, control theory and systems theory, at least in its first-order form...
.
One of the theorists who can be seen as one of the precursors of systems biology is Ludwig von Bertalanffy
Ludwig von Bertalanffy
Karl Ludwig von Bertalanffy was an Austrian-born biologist known as one of the founders of general systems theory . GST is an interdisciplinary practice that describes systems with interacting components, applicable to biology, cybernetics, and other fields...
with his general systems theory. One of the first numerical simulations in biology was published in 1952 by the British neurophysiologists and Nobel prize winners Alan Lloyd Hodgkin
Alan Lloyd Hodgkin
Sir Alan Lloyd Hodgkin, OM, KBE, PRS was a British physiologist and biophysicist, who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles....
and Andrew Fielding Huxley, who constructed a mathematical model that explained the action potential propagating along the axon of a neuronal cell. Their model described a cellular function emerging from the interaction between two different molecular components, a potassium and a sodium channel, and can therefore be seen as the beginning of computational systems biology. In 1960, Denis Noble
Denis Noble
Denis Noble CBE FRS FRCP is a British biologist who held the Burdon Sanderson Chair of Cardiovascular Physiology at Oxford University from 1984 to 2004 and was appointed Professor Emeritus and co-Director of Computational Physiology. He is one of the pioneers of Systems Biology and developed the...
developed the first computer model of the heart pacemaker.
The formal study of systems biology, as a distinct discipline, was launched by systems theorist Mihajlo Mesarovic in 1966 with an international symposium at the Case Institute of Technology
Case Western Reserve University
Case Western Reserve University is a private research university located in Cleveland, Ohio, USA...
in Cleveland, Ohio entitled "Systems Theory and Biology".
The 1960s and 1970s saw the development of several approaches to study complex molecular systems, such as the Metabolic Control Analysis
Metabolic control analysis
Metabolic control analysis is a mathematical framework for describingmetabolic, signaling and genetic pathways. MCA quantifies how variables,such as fluxes and species concentrations, depend on network parameters....
and the biochemical systems theory
Biochemical systems theory
Biochemical systems theory is a mathematical modelling framework for biochemical systems, based on ordinary differential equations , in which biochemical processes are represented using power-law expansions in the variables of the system....
. The successes of molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
throughout the 1980s, coupled with a skepticism toward theoretical biology, that then promised more than it achieved, caused the quantitative modelling of biological processes to become a somewhat minor field.
However the birth of functional genomics
Functional genomics
Functional genomics is a field of molecular biology that attempts to make use of the vast wealth of data produced by genomic projects to describe gene functions and interactions...
in the 1990s meant that large quantities of high quality data became available, while the computing power exploded, making more realistic models possible. In 1997, the group of Masaru Tomita
Masaru Tomita
is a Japanese molecular biologist and computer scientist, best known as the director of the and/or the inventor of GLR parser algorithm. He is a professor of Keio University, president of the , and the founder and board member of . He is also the co-founder and on the board of directors of .From...
published the first quantitative model of the metabolism of a whole (hypothetical) cell.
Around the year 2000, after Institutes of Systems Biology were established in Seattle and Tokyo, systems biology emerged as a movement in its own right, spurred on by the completion of various genome projects, the large increase in data from the omics (e.g. genomics
Genomics
Genomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
and proteomics
Proteomics
Proteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
) and the accompanying advances in high-throughput experiments and bioinformatics
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
. Since then, various research institutes dedicated to systems biology have been developed. For example, the NIGMS of NIH established a project grant that is currently supporting over ten Systems Biology Centers http://www.systemscenters.org/ in the United States. As of summer 2006, due to a shortage of people in systems biology several doctoral training programs in systems biology have been established in many parts of the world. In that same year, the National Science Foundation
National Science Foundation
The National Science Foundation is a United States government agency that supports fundamental research and education in all the non-medical fields of science and engineering. Its medical counterpart is the National Institutes of Health...
(NSF) put forward a grand challenge for systems biology in the 21st century to build a mathematical model of the whole cell. In 2011, V. A. Shiva Ayyadurai
Shiva Ayyadurai
V. A. Shiva Ayyadurai is an American inventor, scientist, and Faculty Lecturer in Department of Biological Engineering at the Massachusetts Institute of Technology.-Early Years & Education:...
and C. Forbes Dewey, Jr. of Department of Biological Engineering at the Massachusetts Institute of Technology
Massachusetts Institute of Technology
The Massachusetts Institute of Technology is a private research university located in Cambridge, Massachusetts. MIT has five schools and one college, containing a total of 32 academic departments, with a strong emphasis on scientific and technological education and research.Founded in 1861 in...
created CytoSolve, a method to model the whole cell by dynamically integrating multiple molecular pathway models.
Associated disciplines
- PhenomicsPhenomicsPhenomics is an area of biology concerned with the measurement of phenomes — the physical and biochemical traits of organisms — as they change in response to genetic mutation and environmental influences...
: Organismal variation in phenotype as it changes during its life span. - GenomicsGenomicsGenomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
: Organismal deoxyribonucleic acid (DNA) sequence, including intra-organisamal cell specific variation. (i.e. Telomere length variation etc.). - EpigenomicsEpigenomics-Epigenomics:Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell...
/ EpigeneticsEpigeneticsIn biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
: Organismal and corresponding cell specific transcriptomic regulating factors not empirically coded in the genomic sequence. (i.e. DNA methylation, Histone Acetelation etc.). - Transcriptomics: Organismal, tissue or whole cell gene expression measurements by DNA microarrayDNA microarrayA DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
s or serial analysis of gene expressionSerial Analysis of Gene ExpressionSerial analysis of gene expression is a technique used by molecular biologists to produce a snapshot of the messenger RNA population in a sample of interest in the form of small tags that correspond to fragments of those transcripts. The original technique was developed by Dr. Victor Velculescu... - InterferomicsInterferomicsInterferomics is a the study of biological events that take place post-transcriptomic pre-translatomically. It defines one of many levels in an emerging field of Life sciences known as Systems Biology....
: Organismal, tissue, or cell level transcript correcting factors (i.e. RNA interferenceRNA interferenceRNA interference is a process within living cells that moderates the activity of their genes. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing , and quelling. Only after these apparently unrelated processes were fully understood did it become...
) - Translatomics / ProteomicsProteomicsProteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
: Organismal, tissue, or cell level measurements of proteins and peptides via two-dimensional gel electrophoresisTwo-dimensional gel electrophoresisTwo-dimensional gel electrophoresis, abbreviated as 2-DE or 2-D electrophoresis, is a form of gel electrophoresis commonly used to analyze proteins...
, mass spectrometryMass spectrometryMass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
or multi-dimensional protein identification techniques (advanced HPLCHigh-performance liquid chromatographyHigh-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
systems coupled with mass spectrometryMass spectrometryMass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
). Sub disciplines include phosphoproteomicsPhosphoproteomicsPhosphoproteomics is a branch of proteomics that identifies, catalogs, and characterizes proteins containing a phosphate group as a post-translational modification. Phosphorylation is a key reversible modification that regulates protein function, subcellular localization, complex formation,...
, glycoproteomicsGlycoproteomicsGlycoproteomics is a branch of proteomics that identifies, catalogs, and characterizes proteins containing carbohydrates as a post-translational modification....
and other methods to detect chemically modified proteins. - MetabolomicsMetabolomicsMetabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles...
: Organismal, tissue, or cell level measurements of all small-molecules known as metabolites. - GlycomicsGlycomicsGlycomics is the comprehensive study of glycomes , including genetic, physiologic, pathologic, and other aspects. Glycomics "is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology...
: Organismal, tissue, or cell level measurements of carbohydrates. - LipidomicsLipidomicsLipidomics may be defined as the large-scale study of pathways and networks of cellular lipids in biological systems The word "lipidome" is used to describe the complete lipid profile within a cell, tissue or organism and is a subset of the "metabolome" which also includes the three other major...
: Organismal, tissue, or cell level measurements of lipids.
In addition to the identification and quantification of the above given molecules further techniques analyze the dynamics and interactions within a cell. This includes:
- InteractomicsInteractomicsInteractomics is a discipline at the intersection of bioinformatics and biology that deals with studying both the interactions and the consequences of those interactions between and among proteins, and other molecules within a cell. The network of all such interactions is called the Interactome...
: Organismal, tissue, or cell level study of interactions between molecules. Currently the authoritative molecular discipline in this field of study is protein-protein interactions (PPI), although the working definition does not pre-clude inclusion of other molecular disciplines such as those defined here. - NeuroElectroDynamicsNeuroElectroDynamicsNeuroElectroDynamics or NED is the study of the dynamics and interaction of electrical charges in the brain [1]. The word neuroelectrodynamics is derived from neuro- meaning neurons, electro- electric field and -dynamics meaning movement....
: Organismal, brain computing function as a dynamic system, underlying biophysical mechanisms and emerging computation by electrical interactions. - Fluxomics: Organismal, tissue, or cell level measurements of molecular dynamic changes over time.
- BiomicsBiomicsBiomics is the biological study of Biomes, and the processing that data, such as ecological communities of plants, animals, and soil organisms.-Uses:...
: systems analysis of the biomeBiomeBiomes are climatically and geographically defined as similar climatic conditions on the Earth, such as communities of plants, animals, and soil organisms, and are often referred to as ecosystems. Some parts of the earth have more or less the same kind of abiotic and biotic factors spread over a...
.
The investigations are frequently combined with large-scale perturbation methods, including gene-based (RNAi
RNAI
RNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...
, mis-expression of wild type and mutant genes) and chemical approaches using small molecule libraries. Robots and automated sensors enable such large-scale experimentation and data acquisition. These technologies are still emerging and many face problems that the larger the quantity of data produced, the lower the quality. A wide variety of quantitative scientists (computational biologists, statisticians, mathematicians, computer scientists, engineers, and physicists) are working to improve the quality of these approaches and to create, refine, and retest the models to accurately reflect observations.
The systems biology approach often involves the development of mechanistic models, such as the reconstruction of dynamic systems from the quantitative properties of their elementary building blocks. For instance, a cellular network can be modelled mathematically using methods coming from chemical kinetics and control theory. Due to the large number of parameters, variables and constraints in cellular networks, numerical and computational techniques are often used.
Other aspects of computer science and informatics are also used in systems biology. These include:
- New forms of computational model, such as the use of process calculi to model biological processes (notable approaches include stochastic
-calculus, BioAmbients, Beta Binders, BioPEPA and Brane calculus) and constraintConstraint programmingConstraint programming is a programming paradigm wherein relations between variables are stated in the form of constraints. Constraints differ from the common primitives of imperative programming languages in that they do not specify a step or sequence of steps to execute, but rather the properties...
-based modeling. - Integration of information from the literature, using techniques of information extractionInformation extractionInformation extraction is a type of information retrieval whose goal is to automatically extract structured information from unstructured and/or semi-structured machine-readable documents. In most of the cases this activity concerns processing human language texts by means of natural language...
and text miningText miningText mining, sometimes alternately referred to as text data mining, roughly equivalent to text analytics, refers to the process of deriving high-quality information from text. High-quality information is typically derived through the devising of patterns and trends through means such as...
. - Development of online databases and repositories for sharing data and models, approaches to database integration and software interoperability via loose couplingLoose couplingIn computing and systems design a loosely coupled system is one where each of its components has, or makes use of, little or no knowledge of the definitions of other separate components. The notion was introduced into organizational studies by Karl Weick...
of software, websites and databases, or commercial suits. - Development of syntactically and semantically sound ways of representing biological models.
See also
- BioinformaticsBioinformaticsBioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
- Computational biologyComputational biologyComputational biology involves the development and application of data-analytical and theoretical methods, mathematical modeling and computational simulation techniques to the study of biological, behavioral, and social systems...
- List of omics topics in biology
:Category:Systems biologists
- List of systems biology research groups
- Network BiologyNetwork biologyBiological network is any network that applies to biological systems. A network is any system with sub-units that are linked into a whole, such as species units linked into a whole food web...