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Systems biology is the
computational
Computation is any type of arithmetic or non-arithmetic calculation that follows a well-defined model (e.g., an algorithm).
Mechanical or electronic devices (or, historically, people) that perform computations are known as ''computers''. An espe ...
and
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 ...
analysis and modeling of complex
biological system
A biological system is a complex network which connects several biologically relevant entities. Biological organization spans several scales and are determined based different structures depending on what the system is. Examples of biological syst ...
s. It is a
biology
Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...
-based interdisciplinary field of study that focuses on complex interactions within biological systems, using a holistic approach (
holism
Holism () is the idea that various systems (e.g. physical, biological, social) should be viewed as wholes, not merely as a collection of parts. The term "holism" was coined by Jan Smuts in his 1926 book ''Holism and Evolution''."holism, n." OED Onl ...
instead of the more traditional
reductionism
Reductionism is any of several related philosophical ideas regarding the associations between phenomena which can be described in terms of other simpler or more fundamental phenomena. It is also described as an intellectual and philosophical pos ...
) to biological research.
Particularly from the year 2000 onwards, the concept has been used widely in biology in a variety of contexts. The
Human Genome Project
The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both a ...
is an example of applied
systems thinking
Systems thinking is a way of making sense of the complexity of the world by looking at it in terms of wholes and relationships rather than by splitting it down into its parts. It has been used as a way of exploring and developing effective actio ...
in biology which has led to new, collaborative ways of working on problems in the biological field of genetics. One of the aims of systems biology is to model and discover
emergent properties
In philosophy, systems theory, science, and art, emergence occurs when an entity is observed to have properties its parts do not have on their own, properties or behaviors that emerge only when the parts interact in a wider whole.
Emergence ...
, properties of
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s,
tissues and
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 functioning as a
system
A system is a group of Interaction, interacting or interrelated elements that act according to a set of rules to form a unified whole. A system, surrounded and influenced by its environment (systems), environment, is described by its boundaries, ...
whose theoretical description is only possible using techniques of systems biology.
These typically involve
metabolic networks or
cell signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
networks.
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
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 ...
and
metabolites
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
in a
metabolic pathway
In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reac ...
or the heart beats).
As a
paradigm
In science and philosophy, a paradigm () is a distinct set of concepts or thought patterns, including theories, research methods, postulates, and standards for what constitute legitimate contributions to a field.
Etymology
''Paradigm'' comes f ...
, systems biology is usually defined in antithesis to the so-called
reductionist paradigm (
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 ...
), although it is consistent with the
scientific method
The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...
. 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 Noble
Denis Noble (born 16 November 1936) is a British biologist who held the Burdon Sanderson Chair of Cardiovascular Physiology at the University of Oxford from 1984 to 2004 and was appointed Professor Emeritus and co-Director of Computational Phy ...
)
As a series of operational
protocol
Protocol may refer to:
Sociology and politics
* Protocol (politics), a formal agreement between nation states
* Protocol (diplomacy), the etiquette of diplomacy and affairs of state
* Etiquette, a code of personal behavior
Science and technolog ...
s used for performing research, namely a cycle composed of theory,
analytic or
computational model
A computational model uses computer programs to simulate and study complex systems using an algorithmic or mechanistic approach and is widely used in a diverse range of fields spanning from physics, chemistry and biology to economics, psychology, ...
ling 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
Transcriptomics technologies are the techniques used to study an organism's transcriptome, the sum of all of its RNA transcripts. The information content of an organism is recorded in the DNA of its genome and expressed through transcription. He ...
,
metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "systematic study of the unique chemical fingerprin ...
,
proteomics
Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In ...
and
high-throughput techniques are used to collect quantitative data for the construction and validation of models.
As the application of
dynamical systems theory
Dynamical systems theory is an area of 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 ' ...
to
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
. Indeed, the focus on the dynamics of the studied systems is the main conceptual difference between systems biology and
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 ...
.
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.
History
Systems biology was begun as a new field of science around 2000, when the Institute for Systems Biology was established in Seattle in an effort to lure "computational" type people who it was felt were not attracted to the academic settings of the university. The institute did not have a clear definition of what the field actually was: roughly bringing together people from diverse fields to use computers to holistically study biology in new ways.
A Department of Systems Biology at Harvard Medical School was launched in 2003. In 2006 it was predicted that the buzz generated by the "very fashionable" new concept would cause all the major universities to need a systems biology department, thus that there would be careers available for graduates with a modicum of ability in computer programming and biology.
In 2006 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 I ...
put forward a challenge to build a mathematical model of the whole cell. In 2012 the first whole-cell model of ''
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 ...
'' was achieved by the Karr Laboratory at the Mount Sinai School of Medicine in New York. The whole-cell model is able to predict viability of ''M. genitalium'' cells in response to genetic mutations.
An earlier precursor of systems biology, as a distinct discipline, may have been by systems theorist
Mihajlo Mesarovic
Mihajlo D. Mesarovic (Gaj's Latin alphabet, Serbian Latin: ''Mihajlo D. Mesarović'', Serbian Cyrillic: Михајло Д. Месаровић; born 2 July 1928) is a Serbian scientist, who is a professor of Systems Engineering and Mathematics at ...
in 1966 with an international symposium at the
Case Institute of Technology
Case Western Reserve University (CWRU) is a private research university in Cleveland, Ohio. Case Western Reserve was established in 1967, when Western Reserve University, founded in 1826 and named for its location in the Connecticut Western Res ...
in
Cleveland
Cleveland ( ), officially the City of Cleveland, is a city in the U.S. state of Ohio and the county seat of Cuyahoga County. Located in the northeastern part of the state, it is situated along the southern shore of Lake Erie, across the U.S. ...
, Ohio, titled ''Systems Theory and Biology''. Mesarovic predicted that perhaps in the future there would be such as thing as "systems biology".
Other early precursors that focused on the view that biology should be analyzed as a system, rather than a simple collection of parts, were
Metabolic Control Analysis Metabolic control analysis (MCA) is a mathematical framework for describing
metabolic, signaling, and genetic pathways. MCA quantifies how variables,elastsuch as fluxes and species concentrations, depend on network parameters.
In particular, it is a ...
, developed by
Henrik Kacser
Henrik Kacser FRSE (22 September 1918 – 13 March 1995) was a Romanian-born biochemist and geneticist who worked in Britain in the 20th century. Kacser's achievements have been recognised by his election to the Royal Society of Edinburgh i ...
and Jim Burns later thoroughly revised, and
Reinhart Heinrich and
Tom Rapoport
Tom Abraham Rapoport (born June 17, 1947) is a German-American cell biologist who studies protein transport in cells. Currently, he is a professor at Harvard Medical School and a Howard Hughes Medical Institute investigator. Born in Cincinnati, OH ...
, and
Biochemical Systems Theory
Biochemical systems theory is a mathematical modelling framework for biochemical systems, based on ordinary differential equations (ODE), in which biochemical processes are represented using power-law expansions in the variables of the system.
Th ...
developed by
Michael Savageau
According to
Robert Rosen in the 1960s, holistic biology had become passé by the early 20th century, as more empirical science dominated by molecular chemistry had become popular.
Echoing him forty years later in 2006 Kling writes that the success of
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
throughout the 20th century had suppressed holistic computational methods.
By 2011 the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
had made grant money available to support over ten systems biology centers in the United States, but by 2012 Hunter writes that systems biology had not lived up to the hype, having promised more than it achieved, which had caused it to become a somewhat minor field with few practical applications. Nonetheless, proponents hoped that it might once prove more useful in the future.
An important milestone in the development of systems biology has become the international project
Physiome The physiome of an individual's or species' physiological state is the description of its functional behavior. The physiome describes the physiological dynamics of the normal intact organism and is built upon information and
structure (genome, prote ...
.
Associated disciplines
According to the interpretation of systems biology as using large data sets using interdisciplinary tools, a typical application is
metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "systematic study of the unique chemical fingerprin ...
, which is the complete set of all the metabolic products,
metabolites
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
, in the system at the organism, cell, or tissue level.
Items that may be a computer database include:
phenomics Phenomics is the systematic study of traits that make up a phenotype, and was coined by UC Berkeley and LBNL scientist Steven A. Garan. As such, it is a transdisciplinary area of research that involves biology, data sciences, engineering and othe ...
, organismal variation in
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
as it changes during its life span;
genomics
Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...
, organismal
deoxyribonucleic acid (DNA) sequence, including intra-organismal cell specific variation. (i.e.,
telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
length variation);
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. Epigen ...
/
epigenetics
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
, organismal and corresponding cell specific transcriptomic regulating factors not empirically coded in the genomic sequence. (i.e.,
DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
,
Histone acetylation and deacetylation, etc.);
transcriptomics
Transcriptomics technologies are the techniques used to study an organism's transcriptome, the sum of all of its RNA transcripts. The information content of an organism is recorded in the DNA of its genome and expressed through transcription. He ...
, organismal, tissue or whole cell
gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
measurements by
DNA microarray
A DNA microarray (also commonly known as DNA chip or biochip) 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 ...
s or
serial analysis of gene expression
Serial Analysis of Gene Expression (SAGE) is a transcriptomic 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 tra ...
;
interferomics, organismal, tissue, or cell-level transcript correcting factors (i.e.,
RNA interference
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by o ...
),
proteomics
Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In ...
, organismal, tissue, or cell level measurements of proteins and peptides via
two-dimensional gel electrophoresis
Two-dimensional gel electrophoresis, abbreviated as 2-DE or 2-D electrophoresis, is a form of gel electrophoresis commonly used to analyze proteins. Mixtures of proteins are separated by two properties in two dimensions on 2D gels. 2-DE was first ...
,
mass spectrometry
Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is use ...
or multi-dimensional protein identification techniques (advanced
HPLC
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...
systems coupled with
mass spectrometry
Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is use ...
). Sub disciplines include
phosphoproteomics,
glycoproteomics and other methods to detect chemically modified proteins;
glycomics Glycomics is the comprehensive study of glycomes (the entire complement of sugars, whether free or present in more complex molecules of an organism), including genetic, physiologic, pathologic, and other aspects. Glycomics "is the systematic study ...
, organismal, tissue, or cell-level measurements of
carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
s;
lipidomics
Lipidomics is 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, organism, or ecosystem and is a subset of the "metabol ...
, organismal, tissue, or cell level measurements of
lipids
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
.
The molecular interactions within the cell are also studied, this is called
interactomics In molecular biology, an interactome is the whole set of molecular interactions in a particular cell. The term specifically refers to physical interactions among molecules (such as those among proteins, also known as protein–protein interactions ...
. A discipline in this field of study is
protein-protein interactions, although interactomics includes the interactions of other molecules.
Neuroelectrodynamics
Neural coding (or Neural representation) is a neuroscience field concerned with characterising the hypothetical relationship between the stimulus and the individual or ensemble neuronal responses and the relationship among the electrical activity ...
, where the computer's or a brain's computing function as a dynamic system is studied along with its (bio)physical mechanisms; and
fluxomics
Fluxomics describes the various approaches that seek to determine the rates of metabolic reactions within a biological entity. While metabolomics can provide instantaneous information on the metabolites in a biological sample, metabolism is a dyna ...
, measurements of the rates of metabolic reactions in a biological system (cell, tissue, or organism).
In approaching a systems biology problem there are two main approaches. These are the top down and bottom up approach. The top down approach takes as much of the system into account as possible and relies largely on experimental results. The
RNA-Seq
RNA-Seq (named as an abbreviation of RNA sequencing) is a sequencing technique which uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample at a given moment, analyzing the continuously changing c ...
technique is an example of an experimental top down approach. Conversely, the bottom up approach is used to create detailed models while also incorporating experimental data. An example of the bottom up approach is the use of circuit models to describe a simple gene network.
Various technologies utilized to capture dynamic changes in mRNA, proteins, and post-translational modifications.
Mechanobiology, forces and physical properties at all scales, their interplay with other regulatory mechanisms;
biosemiotics, analysis of the system of
sign relation
A sign relation is the basic construct in the theory of signs, also known as semiotics, as developed by Charles Sanders Peirce.
Anthesis
Thus, if a sunflower, in turning towards the sun, becomes by that very act fully capable, without further ...
s of an organism or other biosystems;
Physiomics Physiomics is a systematic study of physiome in biology. Physiomics employs bioinformatics to construct networks of physiological features that are associated with genes, proteins and their networks. A few of the methods for determining individual r ...
, a systematic study of
physiome The physiome of an individual's or species' physiological state is the description of its functional behavior. The physiome describes the physiological dynamics of the normal intact organism and is built upon information and
structure (genome, prote ...
in biology.
Cancer systems biology is an example of the systems biology approach, which can be distinguished by the specific object of study (
tumorigenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...
and
treatment of cancer
Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. ...
). It works with the specific data (patient samples, high-throughput data with particular attention to characterizing
cancer genome in patient tumour samples) and tools (immortalized cancer
cell lines
An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
,
mouse models of tumorigenesis,
xenograft
Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenograft ...
models,
high-throughput sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. The ...
methods, siRNA-based gene knocking down
high-throughput screening
High-throughput screening (HTS) is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handlin ...
s, computational modeling of the consequences of somatic
mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
and
genome instability
Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneu ...
).
The long-term objective of the systems biology of cancer is ability to better diagnose cancer, classify it and better predict the outcome of a suggested treatment, which is a basis for
personalized cancer medicine and
virtual cancer patient in more distant prospective. Significant efforts in computational systems biology of cancer have been made in creating realistic multi-scale ''
in silico
In biology and other experimental sciences, an ''in silico'' experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon' (correct la, in silicio), referring to silicon in computer chips. It ...
'' models of various tumours.
[
]
The systems biology approach often involves the development of
mechanistic
The mechanical philosophy is a form of natural philosophy which compares the universe to a large-scale mechanism (i.e. a machine). The mechanical philosophy is associated with the scientific revolution of early modern Europe. One of the first expo ...
models, such as the reconstruction of
dynamic system
In mathematics, a dynamical system is a system in which a function describes the time dependence of a point in an ambient space. Examples include the mathematical models that describe the swinging of a clock pendulum, the flow of water in a ...
s from the quantitative properties of their elementary building blocks.
For instance, a cellular network can be modelled mathematically using methods coming from
chemical kinetics
Chemical kinetics, also known as reaction kinetics, is the branch of physical chemistry that is concerned with understanding the rates of chemical reactions. It is to be contrasted with chemical thermodynamics, which deals with the direction in wh ...
and
control theory
Control theory is a field of mathematics that deals with the control of dynamical systems in engineered processes and machines. The objective is to develop a model or algorithm governing the application of system inputs to drive the system to a ...
. Due to the large number of parameters, variables and constraints in cellular networks, numerical and computational techniques are often used (e.g.,
flux balance analysis
Flux balance analysis (FBA) is a mathematical method for simulating metabolism in genome-scale reconstructions of metabolic networks. In comparison to traditional methods of modeling, FBA is less intensive in terms of the input data required for c ...
).
Bioinformatics and data analysis
Other aspects of computer science,
informatics
Informatics is the study of computational systems, especially those for data storage and retrieval. According to ACM ''Europe and'' ''Informatics Europe'', informatics is synonymous with computer science and computing as a profession, in which ...
, and statistics are also used in systems biology. These include new forms of computational models, such as the use of
process calculi
In computer science, the process calculi (or process algebras) are a diverse family of related approaches for formally modelling concurrent systems. Process calculi provide a tool for the high-level description of interactions, communications, and ...
to model biological processes (notable approaches include stochastic
π-calculus
In theoretical computer science, the -calculus (or pi-calculus) is a process calculus. The -calculus allows channel names to be communicated along the channels themselves, and in this way it is able to describe concurrent computations whose netw ...
, BioAmbients, Beta Binders, BioPEPA, and Brane calculus) and
constraint-based modeling; integration of information from the literature, using techniques of
information extraction
Information extraction (IE) is the task of automatically extracting structured information from unstructured and/or semi-structured machine-readable documents and other electronically represented sources. In most of the cases this activity concer ...
and
text mining
Text mining, also referred to as ''text data mining'', similar to text analytics, is the process of deriving high-quality information from text. It involves "the discovery by computer of new, previously unknown information, by automatically extract ...
; development of online databases and repositories for sharing data and models, approaches to database integration and software interoperability via
loose coupling
In computing and systems design, a loosely coupled system is one
# in which components are weakly associated (have breakable relationships) with each other, and thus changes in one component least affect existence or performance of another comp ...
of software, websites and databases, or commercial suits; network-based approaches for analyzing high dimensional genomic data sets. For example,
weighted correlation network analysis Weighted correlation network analysis, also known as weighted gene co-expression network analysis (WGCNA), is a widely used data mining method especially for studying biological networks based on pairwise correlations between variables. While it ...
is often used for identifying clusters (referred to as modules), modeling the relationship between clusters, calculating fuzzy measures of cluster (module) membership, identifying intramodular hubs, and for studying cluster preservation in other data sets; pathway-based methods for omics data analysis, e.g. approaches to identify and score pathways with differential activity of their gene, protein, or metabolite members.
Much of the analysis of genomic data sets also include identifying correlations. Additionally, as much of the information comes from different fields, the development of syntactically and semantically sound ways of representing biological models is needed.
Creating biological models
![Toy_Biological_Model](https://upload.wikimedia.org/wikipedia/commons/e/eb/Toy_Biological_Model.jpg)
Researchers begin by choosing a biological pathway and diagramming all of the protein interactions. After determining all of the interactions of the proteins,
mass action kinetics is utilized to describe the speed of the reactions in the system. Mass action kinetics will provide differential equations to model the biological system as a mathematical model in which experiments can determine the parameter values to use in the
differential equation
In mathematics, a differential equation is an equation that relates one or more unknown functions and their derivatives. In applications, the functions generally represent physical quantities, the derivatives represent their rates of change, an ...
s. These parameter values will be the reaction rates of each proteins interaction in the system. This model determines the behavior of certain proteins in biological systems and bring new insight to the specific activities of individual proteins. Sometimes it is not possible to gather all reaction rates of a system. Unknown reaction rates are determined by simulating the model of known parameters and target behavior which provides possible parameter values.
The use of constraint-based reconstruction and analysis (COBRA) methods has become popular among systems biologists to simulate and predict the metabolic phenotypes, using genome-scale models. One of the methods is the flux balance analysis (FBA) approach, by which one can study the biochemical networks and analyze the flow of metabolites through a particular metabolic network, by maximizing the object of interest.
See also
*
Biological computation
The concept of biological computation proposes that living organisms perform computations, and that as such, abstract ideas of information and computation may be key to understanding biology. As a field, biological computation can include the stud ...
*
BioSystems (journal)
*
Computational biology
Computational biology refers to the use of data analysis, mathematical modeling and computational simulations to understand biological systems and relationships. An intersection of computer science, biology, and big data, the field also has fo ...
*
Exposome
An environmental factor, ecological factor or eco factor is any factor, abiotic or biotic, that influences living organisms. Abiotic factors include ambient temperature, amount of sunlight, and pH of the water soil in which an organism lives. Bi ...
*
Interactome In molecular biology, an interactome is the whole set of molecular interactions in a particular cell. The term specifically refers to physical interactions among molecules (such as those among proteins, also known as protein–protein interactions, ...
*
List of omics topics in biology
Inspired by the terms genome and genomics, other words to describe complete biological datasets, mostly sets of biomolecules originating from one organism, have been coined with the suffix '' -ome'' and ''-omics''. Some of these terms are related ...
*
living systems
Living systems are open self-organizing life forms that interact with their environment. These systems are maintained by flows of information, energy and matter.
In the last few decades, some scientists have proposed that a general living systems ...
*
Metabolic network modelling
Metabolic network modelling, also known as metabolic network reconstruction or metabolic pathway analysis, allows for an in-depth insight into the molecular mechanisms of a particular organism. In particular, these models correlate the genome wi ...
*
Modelling biological systems Modelling biological systems is a significant task of systems biology and mathematical biology. Computational systems biology aims to develop and use efficient algorithms, data structures, visualization and communication tools with the goal of comp ...
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Molecular pathological epidemiology Molecular pathological epidemiology (MPE, also molecular pathologic epidemiology) is a discipline combining epidemiology and pathology. It is defined as "epidemiology of molecular pathology and heterogeneity of disease". Pathology and epidemiology s ...
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Network biology
A biological network is a method of representing systems as complex sets of binary interactions or relations between various biological entities. In general, networks or graphs are used to capture relationships between entities or objects. A typi ...
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Network medicine
Network medicine is the application of network science towards identifying, preventing, and treating diseases. This field focuses on using network topology and network dynamics towards identifying diseases and developing medical drugs. Biologica ...
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Synthetic biology
Synthetic biology (SynBio) is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature.
It is a branch of science that encompasses a broad ran ...
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Systems biomedicine
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Systems immunology
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Systems medicine Systems medicine is an interdisciplinary field of study that looks at the systems of the human body as part of an integrated whole, incorporating biochemical, physiological, and environment interactions. Systems medicine draws on systems science an ...
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TIARA (database)
The Integrated Archive of Short-Read and Array (TIARA) database contains Personal genomics, personal genomic information obtained from next generation sequencing techniques and ultra-high-resolution comparative genomic hybridization.
See also
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References
Further reading
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* provides a comparative review of three books:
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External links
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Biological Systems in bio-physics-wiki
{{DEFAULTSORT:Systems Biology
Bioinformatics
Computational fields of study