In silico
Encyclopedia
In silico is an expression used to mean "performed on computer
or via computer simulation
." The phrase was coined in 1989 as an analogy to the Latin phrases in vivo
and in vitro
which are commonly used in biology
(see also systems biology
) and refer to experiments done in living organisms and outside of living organisms, respectively.
), researchers found potential inhibitors to an enzyme associated with cancer activity in silico. Fifty percent of the molecules were later shown to be active inhibitors in vitro. This approach differs from use of expensive high-throughput screening
(HTS) robotic labs to physically test thousands of diverse compounds a day often with an expected hit rate on the order of 1% or less with still fewer expected to be real leads following further testing (see drug discovery
).
to aid in drug discovery with a prime benefit cited as being faster than real time simulated growth rates allowing phenomena of interest to be observed in minutes rather than months. More work can be found that focus on modeling a particular cellular process like, for example, the growth cycle of Caulobacter crescentus
.
These efforts fall far short of an exact, fully predictive, computer model of a cell's entire behavior. Limitations in the understanding of molecular dynamics
and cell biology
as well as the absence of available computer processing power force large simplifying assumptions that constrain the usefulness of present in silico models.
may be stored in sequence database
s, be analyzed (see Sequence analysis
), be digitally altered and/or be used as templates for creating new actual DNA using artificial gene synthesis.
(UNAM) presented the report "DNA
and RNA
Physicochemical Constraints, Cellular Automata and Molecular Evolution". In his talk, Miramontes used the term "in silico" to characterize biological experiments carried out entirely in a computer. The work was later presented by Miramontes as his PhD
dissertation.
In silico has been used in white paper
s written to support the creation of bacterial genome programs by the Commission of the European Community. The first referenced paper where "in silico" appears was written by a French
team in 1991. The first referenced book chapter where "in silico" appears was written by Hans B. Sieburg in 1990 and presented during a Summer School on Complex Systems at the Santa Fe Institute.
The phrase "in silico" originally applied only to computer simulations that modeled natural or laboratory processes (in all the natural sciences), and did not refer to calculations done by computer generically.
. Silex
, meaning flint, is a third declension
Latin word in the nominative case, thus with the root silic- for the other cases, from which words like silica are derived in English. The phrase "in silice" means "in flint". However, the adjective in Latin meaning flint-like is silicius,a,um. Many names of elements with the ending -ium come from this adjectival form, e.g. calx (limestone), calcis (of limestone), calcium (limestone-like). In the end, "in silico" was most likely perceived as catchier, possibly through similarity to the words "vivo" and "vitro", and would not have sounded odd given the general disappearance of classical languages in the present curricula. "In silico" is now almost universal; it even occurs in a journal title (In Silico Biology: http://www.bioinfo.de/isb/).
Although the preposition in is Latin and en Greek, in silico is reasonable from the viewpoint of (ancient) Greek case endings; the "-on" ending for certain elements is from Greek. In Greek, "silicon" would take the form "silico" in such a phrase. Latin typically uses the correct Greek forms for Greek words when they are used with Latin prepositions.
Computer
A computer is a programmable machine designed to sequentially and automatically carry out a sequence of arithmetic or logical operations. The particular sequence of operations can be changed readily, allowing the computer to solve more than one kind of problem...
or via computer simulation
Computer simulation
A computer simulation, a computer model, or a computational model is a computer program, or network of computers, that attempts to simulate an abstract model of a particular system...
." The phrase was coined in 1989 as an analogy to the Latin phrases in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
and in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
which are commonly used in biology
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...
(see also systems biology
Systems biology
Systems biology is a term used to describe a number of trends in bioscience research, and a movement which draws on those trends. Proponents describe systems biology as a biology-based inter-disciplinary study field that focuses on complex interactions in biological systems, claiming that it uses...
) and refer to experiments done in living organisms and outside of living organisms, respectively.
Drug discovery with virtual screening
In silico research in medicine is thought to have the potential to speed the rate of discovery while reducing the need for expensive lab work and clinical trials. One way to achieve this is by producing and screening drug candidates more effectively. In 2010, for example, using the protein docking algorithm EADock (see Protein-ligand dockingProtein-ligand docking
Protein–ligand docking is a molecular modelling technique. The goal of protein-ligand docking is to predict the position and orientation of a ligand when it is bound to a protein receptor or enzyme...
), researchers found potential inhibitors to an enzyme associated with cancer activity in silico. Fifty percent of the molecules were later shown to be active inhibitors in vitro. This approach differs from use of expensive high-throughput screening
High-throughput screening
High-throughput screening is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology and chemistry. Using robotics, data processing and control software, liquid handling devices, and sensitive detectors, High-Throughput Screening allows a...
(HTS) robotic labs to physically test thousands of diverse compounds a day often with an expected hit rate on the order of 1% or less with still fewer expected to be real leads following further testing (see drug discovery
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...
).
Cell models
Efforts have been made to establish computer models of cellular behavior. For example, in 2007 researchers developed an in silico model of tuberculosisTuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
to aid in drug discovery with a prime benefit cited as being faster than real time simulated growth rates allowing phenomena of interest to be observed in minutes rather than months. More work can be found that focus on modeling a particular cellular process like, for example, the growth cycle of Caulobacter crescentus
Caulobacter crescentus
Caulobacter crescentus is a Gram-negative, oligotrophic bacterium widely distributed in fresh water lakes and streams.Caulobacter is an important model organism for studying the regulation of the cell cycle, asymmetric cell division, and cellular differentiation. Caulobacter daughter cells have...
.
These efforts fall far short of an exact, fully predictive, computer model of a cell's entire behavior. Limitations in the understanding of molecular dynamics
Molecular dynamics
Molecular dynamics is a computer simulation of physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a period of time, giving a view of the motion of the atoms...
and cell biology
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...
as well as the absence of available computer processing power force large simplifying assumptions that constrain the usefulness of present in silico models.
Genetics
Digital genetic sequences obtained from DNA sequencingDNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
may be stored in sequence database
Sequence database
In the field of bioinformatics, a sequence database is a large collection of computerized nucleic acid sequences, protein sequences, or other sequences stored on a computer...
s, be analyzed (see Sequence analysis
Sequence analysis
In bioinformatics, the term sequence analysis refers to the process of subjecting a DNA, RNA or peptide sequence to any of a wide range of analytical methods to understand its features, function, structure, or evolution. Methodologies used include sequence alignment, searches against biological...
), be digitally altered and/or be used as templates for creating new actual DNA using artificial gene synthesis.
Other examples
In silico computer-based modeling technologies have also been applied in:- Whole cell analysis of prokaryotic and eukaryotic hosts e.g. E. coli, B. subtilis, yeastYeastYeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
, CHO- or human cell lines - BioprocessBioprocessA bioprocess is any process that uses complete living cells or their components to obtain desired productsTransport of energy and mass is fundamental to many biological and environmental processes...
development and optimization e.g. optimization of product yields - Analysis, interpretation and visualization of heterologousHeterologousIn medicine a heterologous transplant means 'between species' or 'from one species to another'.In cell biology and protein biochemistry, heterologous expression means that a protein is experimentally put into a cell that does not normally make that protein...
data sets from various sources e.g. genomeGenomeIn modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
, transcriptomeTranscriptomeThe transcriptome is the set of all RNA molecules, including mRNA, rRNA, tRNA, and other non-coding RNA produced in one or a population of cells.-Scope:...
or proteomeProteomeThe proteome is the entire set of proteins expressed by a genome, cell, tissue or organism. More specifically, it is the set of expressed proteins in a given type of cells or an organism at a given time under defined conditions. The term is a portmanteau of proteins and genome.The term has been...
data
History
The expression in silico was first used in public in 1989 in the workshop "Cellular Automata: Theory and Applications" in Los Alamos, New Mexico. Pedro Miramontes, a mathematician from National Autonomous University of MexicoNational Autonomous University of Mexico
The Universidad Nacional Autónoma de México is a university in Mexico. UNAM was founded on 22 September 1910 by Justo Sierra as a liberal alternative to the Roman Catholic-sponsored Royal and Pontifical University of Mexico The Universidad Nacional Autónoma de México (UNAM) (National Autonomous...
(UNAM) presented the report "DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
and RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
Physicochemical Constraints, Cellular Automata and Molecular Evolution". In his talk, Miramontes used the term "in silico" to characterize biological experiments carried out entirely in a computer. The work was later presented by Miramontes as his PhD
Doctor of Philosophy
Doctor of Philosophy, abbreviated as Ph.D., PhD, D.Phil., or DPhil , in English-speaking countries, is a postgraduate academic degree awarded by universities...
dissertation.
In silico has been used in white paper
White paper
A white paper is an authoritative report or guide that helps solve a problem. White papers are used to educate readers and help people make decisions, and are often requested and used in politics, policy, business, and technical fields. In commercial use, the term has also come to refer to...
s written to support the creation of bacterial genome programs by the Commission of the European Community. The first referenced paper where "in silico" appears was written by a French
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
team in 1991. The first referenced book chapter where "in silico" appears was written by Hans B. Sieburg in 1990 and presented during a Summer School on Complex Systems at the Santa Fe Institute.
The phrase "in silico" originally applied only to computer simulations that modeled natural or laboratory processes (in all the natural sciences), and did not refer to calculations done by computer generically.
In silico versus in silicio
"In silico" was briefly challenged by "in silicio," which is correct Latin for "in silicon". The Latin term for silicon, silicium, was created at the beginning of the 19th century by BerzeliusJöns Jakob Berzelius
Jöns Jacob Berzelius was a Swedish chemist. He worked out the modern technique of chemical formula notation, and is together with John Dalton, Antoine Lavoisier, and Robert Boyle considered a father of modern chemistry...
. Silex
Silex
Silex is any of various forms of ground stone. In modern contexts the word refers to a finely ground, nearly pure form of silica or silicate....
, meaning flint, is a third declension
Declension
In linguistics, declension is the inflection of nouns, pronouns, adjectives, and articles to indicate number , case , and gender...
Latin word in the nominative case, thus with the root silic- for the other cases, from which words like silica are derived in English. The phrase "in silice" means "in flint". However, the adjective in Latin meaning flint-like is silicius,a,um. Many names of elements with the ending -ium come from this adjectival form, e.g. calx (limestone), calcis (of limestone), calcium (limestone-like). In the end, "in silico" was most likely perceived as catchier, possibly through similarity to the words "vivo" and "vitro", and would not have sounded odd given the general disappearance of classical languages in the present curricula. "In silico" is now almost universal; it even occurs in a journal title (In Silico Biology: http://www.bioinfo.de/isb/).
Although the preposition in is Latin and en Greek, in silico is reasonable from the viewpoint of (ancient) Greek case endings; the "-on" ending for certain elements is from Greek. In Greek, "silicon" would take the form "silico" in such a phrase. Latin typically uses the correct Greek forms for Greek words when they are used with Latin prepositions.
See also
- Virtual screeningVirtual screeningVirtual screening is a computational technique used in drug discovery research. By using computers, it deals with the quick search of large libraries of chemical structures in order to identify those structures which are most likely to bind to a drug target, typically a protein receptor or...
- 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...
- Computational biomodeling
- Folding@homeFolding@homeFolding@home is a distributed computing project designed to use spare processing power on personal computers to perform simulations of disease-relevant protein folding and other molecular dynamics, and to improve on the methods of doing so...
- Cellular modelCellular modelCreating a cellular model has been a particularly challenging task of systems biology and mathematical biology.It involves developing efficient algorithms, data structures, visualization and communication tools to orchestrate the integration of large quantities of biological data with the goal of...
- Nonclinical studiesNonclinical studiesNonclinical or Preclinical studies are research studies that are conducted, typically on animals, before a permit for a clinical trial on humans can be obtained. Preclinical studies serve a vital role in the drug discovery and development processes...
- In silico molecular design programs
- List of Latin phrases
- ex vivoEx vivoEx vivo means that which takes place outside an organism. In science, ex vivo refers to experimentation or measurements done in or on tissue in an artificial environment outside the organism with the minimum alteration of natural conditions...
- in situIn situIn situ is a Latin phrase which translated literally as 'In position'. It is used in many different contexts.-Aerospace:In the aerospace industry, equipment on board aircraft must be tested in situ, or in place, to confirm everything functions properly as a system. Individually, each piece may...
- in uteroIn uteroIn utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...
- in vitroIn vitroIn vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
- in vivoIn vivoIn vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
- in papyroIn papyroin papyro: referring to experiments or studies carried out only on paper. For example, the term may be applied to epidemiological studies that do not involve clinical subjects, such as meta-analysis. The term is similar to phrases such as in vivo, in vitro, or in silico...
- In naturaIn naturaIn natura is a phrase to describe conditions present in a non-laboratory environment, to differentiate it from in vivo and ex vivo conditions., -See also:*in vitro*in silico*ex vivo*in situ*in utero*in papyro*in planta...
External links
- World Wide Words: In silico
- CADASTER Seventh Framework Programme project aimed to develop in silico computational methods to minimize experimental tests for REACH Registration, Evaluation, Authorisation and Restriction of Chemicals
- Journal of In Silico Biology