Transistor (updated)

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Assorted discrete transistors. Packages in order from top to bottom: TO-3, TO-126, TO-92, SOT-23.

A transistor is a semiconductor device used to amplify or switch electronic signals and electrical power. It is composed of semiconductor material usually with at least three terminals for connection to an external circuit. A voltage or current applied to one pair of the transistor's terminals controls the current through another pair of terminals. Because the controlled (output) power can be higher than the controlling (input) power, a transistor can amplify a signal. Today, some transistors are packaged individually, but many more are found embedded in integrated circuits.

The transistor is the fundamental building block of modern electronic devices, and is ubiquitous in modern electronic systems. Julius Edgar Lilienfeld patented a field-effect transistor in 1926 but it was not possible to actually construct a working device at that time. The first practically implemented device was a point-contact transistor invented in 1947 by American physicists John Bardeen, Walter Brattain, and William Shockley. The transistor revolutionized the field of electronics, and paved the way for smaller and cheaper radios, calculators, and computers, among other things. The transistor is on the list of IEEE milestones in electronics, and Bardeen, Brattain, and Shockley shared the 1956 Nobel Prize in Physics for their achievement.

Most transistors are made from very pure silicon or germanium, but certain other semiconductor materials can also be used. A transistor may have only one kind of charge carrier, in a field effect transistor, or may have two kinds of charge carriers in bipolar junction transistor devices. Compared with the vacuum tube, transistors are generally smaller, and require less power to operate. Certain vacuum tubes have advantages over transistors at very high operating frequencies or high operating voltages. Many types of transistors are made to standardized specifications by multiple manufacturers.

History

A replica of the first working transistor.

 

The thermionic triode, a vacuum tube invented in 1907, enabled amplified radio technology and long-distance telephony. The triode, however, was a fragile device that consumed a substantial amount of power. In 1909 physicist William Eccles discovered the crystal diode oscillator. Physicist Julius Edgar Lilienfeld filed a patent for a field-effect transistor (FET) in Canada in 1925, which was intended to be a solid-state replacement for the triode. Lilienfeld also filed identical patents in the United States in 1926 and 1928. However, Lilienfeld did not publish any research articles about his devices nor did his patents cite any specific examples of a working prototype. Because the production of high-quality semiconductor materials was still decades away, Lilienfeld's solid-state amplifier ideas would not have found practical use in the 1920s and 1930s, even if such a device had been built. In 1934, German inventor Oskar Heil patented a similar device in Europe.

John Bardeen, William Shockley and Walter Brattain at Bell Labs, 1948.

 

From November 17, 1947, to December 23, 1947, John Bardeen and Walter Brattain at AT&T's Bell Labs in Murray Hill, New Jersey of the United States performed experiments and observed that when two gold point contacts were applied to a crystal of germanium, a signal was produced with the output power greater than the input. Solid State Physics Group leader William Shockley saw the potential in this, and over the next few months worked to greatly expand the knowledge of semiconductors. The term transistor was coined by John R. Pierce as a contraction of the term transresistance. According to Lillian Hoddeson and Vicki Daitch, authors of a biography of John Bardeen, Shockley had proposed that Bell Labs' first patent for a transistor should be based on the field-effect and that he be named as the inventor. Having unearthed Lilienfeld’s patents that went into obscurity years earlier, lawyers at Bell Labs advised against Shockley's proposal because the idea of a field-effect transistor that used an electric field as a "grid" was not new. Instead, what Bardeen, Brattain, and Shockley invented in 1947 was the first point-contact transistor. In acknowledgement of this accomplishment, Shockley, Bardeen, and Brattain were jointly awarded the 1956 Nobel Prize in Physics "for their researches on semiconductors and their discovery of the transistor effect".

Herbert F. Mataré (1950)

 

In 1948, the point-contact transistor was independently invented by German physicists Herbert Mataré and Heinrich Welker while working at the Compagnie des Freins et Signaux, a Westinghouse subsidiary located in Paris. Mataré had previous experience in developing crystal rectifiers from silicon and germanium in the German radar effort during World War II. Using this knowledge, he began researching the phenomenon of "interference" in 1947. By June 1948, witnessing currents flowing through point-contacts, Mataré produced consistent results using samples of germanium produced by Welker, similar to what Bardeen and Brattain had accomplished earlier in December 1947. Realizing that Bell Labs' scientists had already invented the transistor before them, the company rushed to get its "transistron" into production for amplified use in France's telephone network.

The first bipolar junction transistors were invented by Bell Labs' William Shockley, which applied for patent (2,569,347) on June 26, 1948. On April 12, 1950, Bell Labs chemists Gordon Teal and Morgan Sparks had successfully produced a working bipolar NPN junction amplifying germanium transistor. Bell Labs had announced the discovery of this new "sandwich" transistor in a press release on July 4, 1951.

Philco surface-barrier transistor developed and produced in 1953

 

The first high-frequency transistor was the surface-barrier germanium transistor developed by Philco in 1953, capable of operating up to 60 MHz. These were made by etching depressions into an N-type germanium base from both sides with jets of Indium(III) sulfate until it was a few ten-thousandths of an inch thick. Indium electroplated into the depressions formed the collector and emitter.

The first "prototype" pocket transistor radio was shown by INTERMETALL (a company founded by Herbert Mataré in 1952) at the Internationale Funkausstellung Düsseldorf between August 29, 1953 and September 9, 1953.

The first "production" pocket transistor radio was the Regency TR-1, released in October 1954. Produced as a joint venture between the Regency Division of Industrial Development Engineering Associates, I.D.E.A. and Texas Instruments of Dallas Texas, the TR-1 was manufactured in Indianapolis, Indiana. It was a near pocket-sized radio featuring 4 transistors and one germanium diode. The industrial design was outsourced to the Chicago firm of Painter, Teague and Petertil. It was initially released in one of four different colours: black, bone white, red, and gray. Other colours were to shortly follow.

The first "production" all-transistor car radio was developed by Chrysler and Philco corporations and it was announced in the April 28th 1955 edition of the Wall Street Journal. Chrysler had made the all-transistor car radio, Mopar model 914HR, available as an option starting in fall 1955 for its new line of 1956 Chrysler and Imperial cars which first hit the dealership showroom floors on October 21, 1955.

The first working silicon transistor was developed at Bell Labs on January 26, 1954 by Morris Tanenbaum. The first commercial silicon transistor was produced by Texas Instruments in 1954. This was the work of Gordon Teal, an expert in growing crystals of high purity, who had previously worked at Bell Labs. The first MOSFET actually built was by Kahng and Atalla at Bell Labs in 1960.

Importance

A Darlington transistor opened up so the actual transistor chip (the small square) can be seen inside. A Darlington transistor is effectively two transistors on the same chip. One transistor is much larger than the other, but both are large in comparison to transistors in large-scale integration because this particular example is intended for power applications.

 

The transistor is the key active component in practically all modern electronics. Many consider it to be one of the greatest inventions of the 20th century. Its importance in today's society rests on its ability to be mass-produced using a highly automated process (semiconductor device fabrication) that achieves astonishingly low per-transistor costs. The invention of the first transistor at Bell Labs was named an IEEE Milestone in 2009.

Although several companies each produce over a billion individually packaged (known as discrete) transistors every year, the vast majority of transistors are now produced in integrated circuits (often shortened to IC, microchips or simply chips), along with diodes, resistors, capacitors and other electronic components, to produce complete electronic circuits. A logic gate consists of up to about twenty transistors whereas an advanced microprocessor, as of 2009, can use as many as 3 billion transistors (MOSFETs). "About 60 million transistors were built in 2002… for [each] man, woman, and child on Earth."

The transistor's low cost, flexibility, and reliability have made it a ubiquitous device. Transistorized mechatronic circuits have replaced electromechanical devices in controlling appliances and machinery. It is often easier and cheaper to use a standard microcontroller and write a computer program to carry out a control function than to design an equivalent mechanical system to control that same function.

Simplified operation

A simple circuit diagram to show the labels of a n–p–n bipolar transistor.

 

The essential usefulness of a transistor comes from its ability to use a small signal applied between one pair of its terminals to control a much larger signal at another pair of terminals. This property is called gain. It can produce a stronger output signal, a voltage or current, which is proportional to a weaker input signal; that is, it can act as an amplifier. Alternatively, the transistor can be used to turn current on or off in a circuit as an electrically controlled switch, where the amount of current is determined by other circuit elements. 

There are two types of transistors, which have slight differences in how they are used in a circuit. A bipolar transistor has terminals labeled base, collector, and emitter. A small current at the base terminal (that is, flowing between the base and the emitter) can control or switch a much larger current between the collector and emitter terminals. For a field-effect transistor, the terminals are labeled gate, source, and drain, and a voltage at the gate can control a current between source and drain. 

The image represents a typical bipolar transistor in a circuit. Charge will flow between emitter and collector terminals depending on the current in the base. Because internally the base and emitter connections behave like a semiconductor diode, a voltage drop develops between base and emitter while the base current exists. The amount of this voltage depends on the material the transistor is made from, and is referred to as V_BE.

Transistor as a switch

BJT used as an electronic switch, in grounded-emitter configuration.

 

Transistors are commonly used in digital circuits as electronic switches which can be either in an "on" or "off" state, both for high-power applications such as switched-mode power supplies and for low-power applications such as logic gates. Important parameters for this application include the current switched, the voltage handled, and the switching speed, characterized by the rise and fall times. 

In a grounded-emitter transistor circuit, such as the light-switch circuit shown, as the base voltage rises, the emitter and collector currents rise exponentially. The collector voltage drops because of reduced resistance from collector to emitter. If the voltage difference between the collector and emitter were zero (or near zero), the collector current would be limited only by the load resistance (light bulb) and the supply voltage. This is called saturation because current is flowing from collector to emitter freely. When saturated, the switch is said to be on.

Providing sufficient base drive current is a key problem in the use of bipolar transistors as switches. The transistor provides current gain, allowing a relatively large current in the collector to be switched by a much smaller current into the base terminal. The ratio of these currents varies depending on the type of transistor, and even for a particular type, varies depending on the collector current. In the example light-switch circuit shown, the resistor is chosen to provide enough base current to ensure the transistor will be saturated. 

In a switching circuit, the idea is to simulate, as near as possible, the ideal switch having the properties of open circuit when off, short circuit when on, and an instantaneous transition between the two states. Parameters are chosen such that the "off" output is limited to leakage currents too small to affect connected circuitry; the resistance of the transistor in the "on" state is too small to affect circuitry; and the transition between the two states is fast enough not to have a detrimental effect.

Transistor as an amplifier

Amplifier circuit, common-emitter configuration with a voltage-divider bias circuit.

 

The common-emitter amplifier is designed so that a small change in voltage (V_in) changes the small current through the base of the transistor; the transistor's current amplification combined with the properties of the circuit means that small swings in V_in produce large changes in V_out. 

Various configurations of single transistor amplifier are possible, with some providing current gain, some voltage gain, and some both. 

From mobile phones to televisions, vast numbers of products include amplifiers for sound reproduction, radio transmission, and signal processing. The first discrete-transistor audio amplifiers barely supplied a few hundred milliwatts, but power and audio fidelity gradually increased as better transistors became available and amplifier architecture evolved. 

Modern transistor audio amplifiers of up to a few hundred watts are common and relatively inexpensive.

Comparison with vacuum tubes

Before transistors were developed, vacuum (electron) tubes (or in the UK "thermionic valves" or just "valves") were the main active components in electronic equipment.

Advantages

The key advantages that have allowed transistors to replace vacuum tubes in most applications are

• no cathode heater (which produces the characteristic orange glow of tubes), reducing power consumption, eliminating delay as tube heaters warm up, and immune from cathode poisoning and depletion;
• very small size and weight, reducing equipment size;
• large numbers of extremely small transistors can be manufactured as a single integrated circuit;
• low operating voltages compatible with batteries of only a few cells;
• circuits with greater energy efficiency are usually possible. For low-power applications (e.g., voltage amplification) in particular, energy consumption can be very much less than for tubes;
• complementary devices available, providing design flexibility including complementary-symmetry circuits, not possible with vacuum tubes;
• very low sensitivity to mechanical shock and vibration, providing physical ruggedness and virtually eliminating shock-induced spurious signals (e.g., microphonics in audio applications);
• not susceptible to breakage of a glass envelope, leakage, outgassing, and other physical damage.

Limitations

Transistors have the following limitations:

• high-power, high-frequency operation, such as that used in over-the-air television broadcasting, is better achieved in vacuum tubes due to improved electron mobility in a vacuum;
• solid-state devices are susceptible to damage from very brief electrical and thermal events, including electrostatic discharge in handling; vacuum tubes are electrically much more rugged;
• sensitivity to radiation and cosmic rays (special radiation-hardened chips are used for spacecraft devices);
• vacuum tubes in audio applications create significant lower-harmonic distortion, the so-called tube sound, which some people prefer.

Types

Transistors are categorized by

• semiconductor material: the metalloids germanium (first used in 1947) and silicon (first used in 1954)—in amorphous, polycrystalline and monocrystalline form—, the compounds gallium arsenide (1966) and silicon carbide (1997), the alloy silicon-germanium (1989), the allotrope of carbon graphene (research ongoing since 2004), etc. (see Semiconductor material);
• structure: BJT, JFET, IGFET (MOSFET), insulated-gate bipolar transistor (IGBT), "other types";
• electrical polarity (positive and negative): n–p–n, p–n–p (BJTs), n-channel, p-channel (FETs);
• maximum power rating: low, medium, high;
• maximum operating frequency: low, medium, high, radio (RF), microwave frequency (the maximum effective frequency of a transistor in a common-emitter or common-source circuit is denoted by the term f_T, an abbreviation for transition frequency—the frequency of transition is the frequency at which the transistor yields unity voltage gain)
• application: switch, general purpose, audio, high voltage, super-beta, matched pair;
• physical packaging: through-hole metal, through-hole plastic, surface mount, ball grid array, power modules (see Packaging);
• amplification factor h_FE, β_F (transistor beta) or g_m (transconductance).

Hence, a particular transistor may be described as silicon, surface-mount, BJT, n–p–n, low-power, high-frequency switch. 

A popular way to remember which symbol represents which type of transistor is to look at the arrow and how it is arranged. Within an NPN transistor symbol, the arrow will Not Point iN. Conversely, within the PNP symbol you see that the arrow Points iN Proudly.

Bipolar junction transistor (BJT)

Bipolar transistors are so named because they conduct by using both majority and minority carriers. The bipolar junction transistor, the first type of transistor to be mass-produced, is a combination of two junction diodes, and is formed of either a thin layer of p-type semiconductor sandwiched between two n-type semiconductors (an n–p–n transistor), or a thin layer of n-type semiconductor sandwiched between two p-type semiconductors (a p–n–p transistor). This construction produces two p–n junctions: a base–emitter junction and a base–collector junction, separated by a thin region of semiconductor known as the base region (two junction diodes wired together without sharing an intervening semiconducting region will not make a transistor).

BJTs have three terminals, corresponding to the three layers of semiconductor—an emitter, a base, and a collector. They are useful in amplifiers because the currents at the emitter and collector are controllable by a relatively small base current. In an n–p–n transistor operating in the active region, the emitter–base junction is forward biased (electrons and holes recombine at the junction), and the base-collector junction is reverse biased (electrons and holes are formed at, and move away from the junction), and electrons are injected into the base region. Because the base is narrow, most of these electrons will diffuse into the reverse-biased base–collector junction and be swept into the collector; perhaps one-hundredth of the electrons will recombine in the base, which is the dominant mechanism in the base current. As well, as the base is lightly doped (in comparison to the emitter and collector regions), recombination rates are low, permitting more carriers to diffuse across the base region. By controlling the number of electrons that can leave the base, the number of electrons entering the collector can be controlled. Collector current is approximately β (common-emitter current gain) times the base current. It is typically greater than 100 for small-signal transistors but can be smaller in transistors designed for high-power applications. 

Unlike the field-effect transistor (see below), the BJT is a low-input-impedance device. Also, as the base–emitter voltage (V_BE) is increased the base–emitter current and hence the collector–emitter current (I_CE) increase exponentially according to the Shockley diode model and the Ebers-Moll model. Because of this exponential relationship, the BJT has a higher transconductance than the FET.

Bipolar transistors can be made to conduct by exposure to light, because absorption of photons in the base region generates a photocurrent that acts as a base current; the collector current is approximately β times the photocurrent. Devices designed for this purpose have a transparent window in the package and are called phototransistors.

Field-effect transistor (FET)

Operation of a FET and its Id-Vg curve. At first, when no gate voltage is applied. There is no inversion electron in the channel, the device is OFF. As gate voltage increase, inversion electron density in the channel increase, current increase, the device turns on.

 

The field-effect transistor, sometimes called a unipolar transistor, uses either electrons (in n-channel FET) or holes (in p-channel FET) for conduction. The four terminals of the FET are named source, gate, drain, and body (substrate). On most FETs, the body is connected to the source inside the package, and this will be assumed for the following description. 

In a FET, the drain-to-source current flows via a conducting channel that connects the source region to the drain region. The conductivity is varied by the electric field that is produced when a voltage is applied between the gate and source terminals; hence the current flowing between the drain and source is controlled by the voltage applied between the gate and source. As the gate–source voltage (V_GS) is increased, the drain–source current (I_DS) increases exponentially for V_GS below threshold, and then at a roughly quadratic rate (I_DS ∝ (V_GS − V_T)²) (where V_T is the threshold voltage at which drain current begins) in the "space-charge-limited" region above threshold. A quadratic behavior is not observed in modern devices, for example, at the 65 nm technology node.

For low noise at narrow bandwidth the higher input resistance of the FET is advantageous. 

FETs are divided into two families: junction FET (JFET) and insulated gate FET (IGFET). The IGFET is more commonly known as a metal–oxide–semiconductor FET (MOSFET), reflecting its original construction from layers of metal (the gate), oxide (the insulation), and semiconductor. Unlike IGFETs, the JFET gate forms a p–n diode with the channel which lies between the source and drain. Functionally, this makes the n-channel JFET the solid-state equivalent of the vacuum tube triode which, similarly, forms a diode between its grid and cathode. Also, both devices operate in the depletion mode, they both have a high input impedance, and they both conduct current under the control of an input voltage. 

Metal–semiconductor FETs (MESFETs) are JFETs in which the reverse biased p–n junction is replaced by a metal–semiconductor junction. These, and the HEMTs (high-electron-mobility transistors, or HFETs), in which a two-dimensional electron gas with very high carrier mobility is used for charge transport, are especially suitable for use at very high frequencies (microwave frequencies; several GHz). 

FETs are further divided into depletion-mode and enhancement-mode types, depending on whether the channel is turned on or off with zero gate-to-source voltage. For enhancement mode, the channel is off at zero bias, and a gate potential can "enhance" the conduction. For the depletion mode, the channel is on at zero bias, and a gate potential (of the opposite polarity) can "deplete" the channel, reducing conduction. For either mode, a more positive gate voltage corresponds to a higher current for n-channel devices and a lower current for p-channel devices. Nearly all JFETs are depletion-mode because the diode junctions would forward bias and conduct if they were enhancement-mode devices; most IGFETs are enhancement-mode types.

Usage of bipolar and field-effect transistors

The bipolar junction transistor (BJT) was the most commonly used transistor in the 1960s and 70s. Even after MOSFETs became widely available, the BJT remained the transistor of choice for many analog circuits such as amplifiers because of their greater linearity and ease of manufacture. In integrated circuits, the desirable properties of MOSFETs allowed them to capture nearly all market share for digital circuits. Discrete MOSFETs can be applied in transistor applications, including analog circuits, voltage regulators, amplifiers, power transmitters and motor drivers.

Other transistor types

Transistor symbol created on Portuguese pavement in the University of Aveiro.

• Bipolar junction transistor (BJT):
  • heterojunction bipolar transistor, up to several hundred GHz, common in modern ultrafast and RF circuits;
  • Schottky transistor;
  • avalanche transistor:
  • Darlington transistors are two BJTs connected together to provide a high current gain equal to the product of the current gains of the two transistors;
  • insulated-gate bipolar transistors (IGBTs) use a medium-power IGFET, similarly connected to a power BJT, to give a high input impedance. Power diodes are often connected between certain terminals depending on specific use. IGBTs are particularly suitable for heavy-duty industrial applications. The ASEA Brown Boveri (ABB) 5SNA2400E170100, intended for three-phase power supplies, houses three n–p–n IGBTs in a case measuring 38 by 140 by 190 mm and weighing 1.5 kg. Each IGBT is rated at 1,700 volts and can handle 2,400 amperes;
  • Phototransistor.
  • emitter-switched-bipolar-transistor (ESBT) is a monolithic configuration of a high voltage bipolar transistor and a low voltage power MOSFET in cascode topology. It was introduced by STMicroelectronics in the 2000s, and abandoned a few years later around 2012.
  • multiple-emitter transistor, used in transistor–transistor logic and integrated current mirrors;
  • multiple-base transistor, used to amplify very-low-level signals in noisy environments such as the pickup of a record player or radio front ends. Effectively, it is a very large number of transistors in parallel where, at the output, the signal is added constructively, but random noise is added only stochastically.
• Field-effect transistor (FET):
  • carbon nanotube field-effect transistor (CNFET), where the channel material is replaced by a carbon nanotube;
  • junction gate field-effect transistor (JFET), where the gate is insulated by a reverse-biased p–n junction;
  • metal–semiconductor field-effect transistor (MESFET), similar to JFET with a Schottky junction instead of a p–n junction;
    • high-electron-mobility transistor (HEMT);
  • metal–oxide–semiconductor field-effect transistor (MOSFET), where the gate is insulated by a shallow layer of insulator;
  • inverted-T field-effect transistor (ITFET);
  • fin field-effect transistor (FinFET), source/drain region shapes fins on the silicon surface;
  • fast-reverse epitaxial diode field-effect transistor (FREDFET);
  • thin-film transistor, in LCDs;
  • organic field-effect transistor (OFET), in which the semiconductor is an organic compound;
  • ballistic transistor (disambiguation);
  • floating-gate transistor, for non-volatile storage;
  • FETs used to sense environment;
    • ion-sensitive field-effect transistor (IFSET), to measure ion concentrations in solution,
    • electrolyte–oxide–semiconductor field-effect transistor (EOSFET), neurochip,
    • deoxyribonucleic acid field-effect transistor (DNAFET).
• Tunnel field-effect transistor, where it switches by modulating quantum tunnelling through a barrier.
• Diffusion transistor, formed by diffusing dopants into semiconductor substrate; can be both BJT and FET.
• Unijunction transistor, can be used as simple pulse generators. It comprise a main body of either P-type or N-type semiconductor with ohmic contacts at each end (terminals Base1 and Base2). A junction with the opposite semiconductor type is formed at a point along the length of the body for the third terminal (Emitter).
• Single-electron transistors (SET), consist of a gate island between two tunneling junctions. The tunneling current is controlled by a voltage applied to the gate through a capacitor.
• Nanofluidic transistor, controls the movement of ions through sub-microscopic, water-filled channels.
• Multigate devices:
  • tetrode transistor;
  • pentode transistor;
  • trigate transistor (prototype by Intel);
  • dual-gate field-effect transistors have a single channel with two gates in cascode; a configuration optimized for high-frequency amplifiers, mixers, and oscillators.
• Junctionless nanowire transistor (JNT), uses a simple nanowire of silicon surrounded by an electrically isolated "wedding ring" that acts to gate the flow of electrons through the wire.
• Vacuum-channel transistor, when in 2012, NASA and the National Nanofab Center in South Korea were reported to have built a prototype vacuum-channel transistor in only 150 nanometers in size, can be manufactured cheaply using standard silicon semiconductor processing, can operate at high speeds even in hostile environments, and could consume just as much power as a standard transistor.
• Organic electrochemical transistor.
• A Solaristor (from solar cell transistor) is a two-terminal gate-less self-powered phototransistor.

Part numbering standards/specifications

The types of some transistors can be parsed from the part number. There are three major semiconductor naming standards; in each the alphanumeric prefix provides clues to type of the device.

Japanese Industrial Standard (JIS)

The JIS-C-7012 specification for transistor part numbers starts with "2S", e.g. 2SD965, but sometimes the "2S" prefix is not marked on the package – a 2SD965 might only be marked "D965"; a 2SC1815 might be listed by a supplier as simply "C1815". This series sometimes has suffixes (such as "R", "O", "BL", standing for "red", "orange", "blue", etc.) to denote variants, such as tighter h_FE (gain) groupings.

European Electronic Component Manufacturers Association (EECA)

The Pro Electron standard, the European Electronic Component Manufacturers Association part numbering scheme, begins with two letters: the first gives the semiconductor type (A for germanium, B for silicon, and C for materials like GaAs); the second letter denotes the intended use (A for diode, C for general-purpose transistor, etc.). A 3-digit sequence number (or one letter then two digits, for industrial types) follows. With early devices this indicated the case type. Suffixes may be used, with a letter (e.g. "C" often means high h_FE, such as in: BC549C) or other codes may follow to show gain (e.g. BC327-25) or voltage rating (e.g. BUK854-800A). The more common prefixes are: 

Pro Electron / EECA transistor prefix table

Prefix class	Type and usage	Example	Equivalent	Reference
AC	Germanium small-signal AF transistor	AC126	NTE102A	Datasheet
AD	Germanium AF power transistor	AD133	NTE179	Datasheet
AF	Germanium small-signal RF transistor	AF117	NTE160	Datasheet
AL	Germanium RF power transistor	ALZ10	NTE100	Datasheet
AS	Germanium switching transistor	ASY28	NTE101	Datasheet
AU	Germanium power switching transistor	AU103	NTE127	Datasheet
BC	Silicon, small-signal transistor ("general purpose")	BC548	2N3904	Datasheet
BD	Silicon, power transistor	BD139	NTE375	Datasheet
BF	Silicon, RF (high frequency) BJT or FET	BF245	NTE133	Datasheet
BS	Silicon, switching transistor (BJT or MOSFET)	BS170	2N7000	Datasheet
BL	Silicon, high frequency, high power (for transmitters)	BLW60	NTE325	Datasheet
BU	Silicon, high voltage (for CRT horizontal deflection circuits)	BU2520A	NTE2354	Datasheet
CF	Gallium arsenide small-signal microwave transistor (MESFET)	CF739	—	Datasheet
CL	Gallium arsenide microwave power transistor (FET)	CLY10	—	Datasheet

Joint Electron Device Engineering Council (JEDEC)

The JEDEC EIA370 transistor device numbers usually start with "2N", indicating a three-terminal device (dual-gate field-effect transistors are four-terminal devices, so begin with 3N), then a 2, 3 or 4-digit sequential number with no significance as to device properties (although early devices with low numbers tend to be germanium). For example, 2N3055 is a silicon n–p–n power transistor, 2N1301 is a p–n–p germanium switching transistor. A letter suffix (such as "A") is sometimes used to indicate a newer variant, but rarely gain groupings.

Proprietary

Manufacturers of devices may have their own proprietary numbering system, for example CK722. Since devices are second-sourced, a manufacturer's prefix (like "MPF" in MPF102, which originally would denote a Motorola FET) now is an unreliable indicator of who made the device. Some proprietary naming schemes adopt parts of other naming schemes, for example a PN2222A is a (possibly Fairchild Semiconductor) 2N2222A in a plastic case (but a PN108 is a plastic version of a BC108, not a 2N108, while the PN100 is unrelated to other xx100 devices). 

Military part numbers sometimes are assigned their own codes, such as the British Military CV Naming System.

Manufacturers buying large numbers of similar parts may have them supplied with "house numbers", identifying a particular purchasing specification and not necessarily a device with a standardized registered number. For example, an HP part 1854,0053 is a (JEDEC) 2N2218 transistor which is also assigned the CV number: CV7763

Naming problems

With so many independent naming schemes, and the abbreviation of part numbers when printed on the devices, ambiguity sometimes occurs. For example, two different devices may be marked "J176" (one the J176 low-power JFET, the other the higher-powered MOSFET 2SJ176). 

As older "through-hole" transistors are given surface-mount packaged counterparts, they tend to be assigned many different part numbers because manufacturers have their own systems to cope with the variety in pinout arrangements and options for dual or matched n–p–n + p–n–p devices in one pack. So even when the original device (such as a 2N3904) may have been assigned by a standards authority, and well known by engineers over the years, the new versions are far from standardized in their naming.

Construction

Semiconductor material

Semiconductor material characteristics

Semiconductor material	Junction forward voltage V @ 25 °C	Electron mobility m2/(V·s) @ 25 °C	Hole mobility m2/(V·s) @ 25 °C	Max. junction temp. °C
Ge	0.27	0.39	0.19	70 to 100
Si	0.71	0.14	0.05	150 to 200
GaAs	1.03	0.85	0.05	150 to 200
Al-Si junction	0.3	—	—	150 to 200

The first BJTs were made from germanium (Ge). Silicon (Si) types currently predominate but certain advanced microwave and high-performance versions now employ the compound semiconductor material gallium arsenide (GaAs) and the semiconductor alloy silicon germanium (SiGe). Single element semiconductor material (Ge and Si) is described as elemental. 

Rough parameters for the most common semiconductor materials used to make transistors are given in the adjacent table; these parameters will vary with increase in temperature, electric field, impurity level, strain, and sundry other factors. 

The junction forward voltage is the voltage applied to the emitter–base junction of a BJT in order to make the base conduct a specified current. The current increases exponentially as the junction forward voltage is increased. The values given in the table are typical for a current of 1 mA (the same values apply to semiconductor diodes). The lower the junction forward voltage the better, as this means that less power is required to "drive" the transistor. The junction forward voltage for a given current decreases with increase in temperature. For a typical silicon junction the change is −2.1 mV/°C. In some circuits special compensating elements (sensistors) must be used to compensate for such changes. 

The density of mobile carriers in the channel of a MOSFET is a function of the electric field forming the channel and of various other phenomena such as the impurity level in the channel. Some impurities, called dopants, are introduced deliberately in making a MOSFET, to control the MOSFET electrical behavior. 

The electron mobility and hole mobility columns show the average speed that electrons and holes diffuse through the semiconductor material with an electric field of 1 volt per meter applied across the material. In general, the higher the electron mobility the faster the transistor can operate. The table indicates that Ge is a better material than Si in this respect. However, Ge has four major shortcomings compared to silicon and gallium arsenide:

• its maximum temperature is limited;
• it has relatively high leakage current;
• it cannot withstand high voltages;
• it is less suitable for fabricating integrated circuits.

Because the electron mobility is higher than the hole mobility for all semiconductor materials, a given bipolar n–p–n transistor tends to be swifter than an equivalent p–n–p transistor. GaAs has the highest electron mobility of the three semiconductors. It is for this reason that GaAs is used in high-frequency applications. A relatively recent FET development, the high-electron-mobility transistor (HEMT), has a heterostructure (junction between different semiconductor materials) of aluminium gallium arsenide (AlGaAs)-gallium arsenide (GaAs) which has twice the electron mobility of a GaAs-metal barrier junction. Because of their high speed and low noise, HEMTs are used in satellite receivers working at frequencies around 12 GHz. HEMTs based on gallium nitride and aluminium gallium nitride (AlGaN/GaN HEMTs) provide a still higher electron mobility and are being developed for various applications. 

Max. junction temperature values represent a cross section taken from various manufacturers' data sheets. This temperature should not be exceeded or the transistor may be damaged. 

Al–Si junction refers to the high-speed (aluminum–silicon) metal–semiconductor barrier diode, commonly known as a Schottky diode. This is included in the table because some silicon power IGFETs have a parasitic reverse Schottky diode formed between the source and drain as part of the fabrication process. This diode can be a nuisance, but sometimes it is used in the circuit.

Packaging

Assorted discrete transistors

 

Soviet KT315b transistors

Discrete transistors can be individually packaged transistors or unpackaged transistor chips (dice). 

Transistors come in many different semiconductor packages (see image). The two main categories are through-hole (or leaded), and surface-mount, also known as surface-mount device (SMD). The ball grid array (BGA) is the latest surface-mount package (currently only for large integrated circuits). It has solder "balls" on the underside in place of leads. Because they are smaller and have shorter interconnections, SMDs have better high-frequency characteristics but lower power rating. 

Transistor packages are made of glass, metal, ceramic, or plastic. The package often dictates the power rating and frequency characteristics. Power transistors have larger packages that can be clamped to heat sinks for enhanced cooling. Additionally, most power transistors have the collector or drain physically connected to the metal enclosure. At the other extreme, some surface-mount microwave transistors are as small as grains of sand. 

Often a given transistor type is available in several packages. Transistor packages are mainly standardized, but the assignment of a transistor's functions to the terminals is not: other transistor types can assign other functions to the package's terminals. Even for the same transistor type the terminal assignment can vary (normally indicated by a suffix letter to the part number, q.e. BC212L and BC212K). 

Nowadays most transistors come in a wide range of SMT packages, in comparison the list of available through-hole packages is relatively small, here is a short list of the most common through-hole transistors packages in alphabetical order: ATV, E-line, MRT, HRT, SC-43, SC-72, TO-3, TO-18, TO-39, TO-92, TO-126, TO220, TO247, TO251, TO262, ZTX851. 

Unpackaged transistor chips (die) may be assembled into hybrid devices. The IBM SLT module of the 1960s is one example of such a hybrid circuit module using glass passivated transistor (and diode) die. Other packaging techniques for discrete transistors as chips include Direct Chip Attach (DCA) and Chip On Board (COB).

Flexible transistors

Researchers have made several kinds of flexible transistors, including organic field-effect transistors. Flexible transistors are useful in some kinds of flexible displays and other flexible electronics.

Gene regulatory network

From Wikipedia, the free encyclopedia

Structure of a gene regulatory network

 

Control process of a gene regulatory network

A gene (or genetic) regulatory network (GRN) is a collection of molecular regulators that interact with each other and with other substances in the cell to govern the gene expression levels of mRNA and proteins. These play a central role in morphogenesis, the creation of body structures, which in turn is central to evolutionary developmental biology (evo-devo). 

The regulator can be DNA, RNA, protein and complexes of these. The interaction can be direct or indirect (through transcribed RNA or translated protein). In general, each mRNA molecule goes on to make a specific protein (or set of proteins). In some cases this protein will be structural, and will accumulate at the cell membrane or within the cell to give it particular structural properties. In other cases the protein will be an enzyme, i.e., a micro-machine that catalyses a certain reaction, such as the breakdown of a food source or toxin. Some proteins though serve only to activate other genes, and these are the transcription factors that are the main players in regulatory networks or cascades. By binding to the promoter region at the start of other genes they turn them on, initiating the production of another protein, and so on. Some transcription factors are inhibitory.

In single-celled organisms, regulatory networks respond to the external environment, optimizing the cell at a given time for survival in this environment. Thus a yeast cell, finding itself in a sugar solution, will turn on genes to make enzymes that process the sugar to alcohol. This process, which we associate with wine-making, is how the yeast cell makes its living, gaining energy to multiply, which under normal circumstances would enhance its survival prospects.

In multicellular animals the same principle has been put in the service of gene cascades that control body-shape. Each time a cell divides, two cells result which, although they contain the same genome in full, can differ in which genes are turned on and making proteins. Sometimes a 'self-sustaining feedback loop' ensures that a cell maintains its identity and passes it on. Less understood is the mechanism of epigenetics by which chromatin modification may provide cellular memory by blocking or allowing transcription. A major feature of multicellular animals is the use of morphogen gradients, which in effect provide a positioning system that tells a cell where in the body it is, and hence what sort of cell to become. A gene that is turned on in one cell may make a product that leaves the cell and diffuses through adjacent cells, entering them and turning on genes only when it is present above a certain threshold level. These cells are thus induced into a new fate, and may even generate other morphogens that signal back to the original cell. Over longer distances morphogens may use the active process of signal transduction. Such signalling controls embryogenesis, the building of a body plan from scratch through a series of sequential steps. They also control and maintain adult bodies through feedback processes, and the loss of such feedback because of a mutation can be responsible for the cell proliferation that is seen in cancer. In parallel with this process of building structure, the gene cascade turns on genes that make structural proteins that give each cell the physical properties it needs.

Overview

At one level, biological cells can be thought of as "partially mixed bags" of biological chemicals – in the discussion of gene regulatory networks, these chemicals are mostly the messenger RNAs (mRNAs) and proteins that arise from gene expression. These mRNA and proteins interact with each other with various degrees of specificity. Some diffuse around the cell. Others are bound to cell membranes, interacting with molecules in the environment. Still others pass through cell membranes and mediate long range signals to other cells in a multi-cellular organism. These molecules and their interactions comprise a gene regulatory network. A typical gene regulatory network looks something like this: 

Example of a regulatory network

 

The nodes of this network can represent genes, proteins, mRNAs, protein/protein complexes or cellular processes. Nodes that are depicted as lying along vertical lines are associated with the cell/environment interfaces, while the others are free-floating and can diffuse. Edges between nodes represent interactions between the nodes, that can correspond to individual molecular reactions between DNA, mRNA, miRNA, proteins or molecular processes through which the products of one gene affect those of another, though the lack of experimentally obtained information often implies that some reactions are not modeled at such a fine level of detail. These interactions can be inductive (usually represented by arrowheads or the + sign), with an increase in the concentration of one leading to an increase in the other, inhibitory (represented with filled circles, blunt arrows or the minus sign), with an increase in one leading to a decrease in the other, or dual, when depending of the circumstances the regulator can activate or inhibit the target node. The nodes can regulate themselves directly or indirectly, creating feedback loops, which form cyclic chains of dependencies in the topological network. The network structure is an abstraction of the system's molecular or chemical dynamics, describing the manifold ways in which one substance affects all the others to which it is connected. In practice, such GRNs are inferred from the biological literature on a given system and represent a distillation of the collective knowledge about a set of related biochemical reactions. To speed up the manual curation of GRNs, some recent efforts try to use text mining, curated databases, network inference from massive data, model checking and other information extraction technologies for this purpose.

Genes can be viewed as nodes in the network, with input being proteins such as transcription factors, and outputs being the level of gene expression. The value of the node depends of a function which depends in the value of its regulators in previous time steps (in the Boolean network described below these are Boolean functions, typically AND, OR, and NOT). These functions have been interpreted as performing a kind of information processing within the cell, which determines cellular behavior. The basic drivers within cells are concentrations of some proteins, which determine both spatial (location within the cell or tissue) and temporal (cell cycle or developmental stage) coordinates of the cell, as a kind of "cellular memory". The gene networks are only beginning to be understood, and it is a next step for biology to attempt to deduce the functions for each gene "node", to help understand the behavior of the system in increasing levels of complexity, from gene to signaling pathway, cell or tissue level.

Mathematical models of GRNs have been developed to capture the behavior of the system being modeled, and in some cases generate predictions corresponding with experimental observations. In some other cases, models have proven to make accurate novel predictions, which can be tested experimentally, thus suggesting new approaches to explore in an experiment that sometimes wouldn't be considered in the design of the protocol of an experimental laboratory. Modeling techniques include differential equations (ODEs), Boolean networks, Petri nets, Bayesian networks, graphical Gaussian models, Stochastic, and Process Calculi. Conversely, techniques have been proposed for generating models of GRNs that best explain a set of time series observations. Recently it has been shown that ChIP-seq signal of Histone modification are more correlated with transcription factor motifs at promoters in comparison to RNA level. Hence it is proposed that time-series histone modification ChIP-seq could provide more reliable inference of gene-regulatory networks in comparison to methods based on expression levels.

Structure and evolution

Global feature

Gene regulatory networks are generally thought to be made up of a few highly connected nodes (hubs) and many poorly connected nodes nested within a hierarchical regulatory regime. Thus gene regulatory networks approximate a hierarchical scale free network topology. This is consistent with the view that most genes have limited pleiotropy and operate within regulatory modules. This structure is thought to evolve due to the preferential attachment of duplicated genes to more highly connected genes. Recent work has also shown that natural selection tends to favor networks with sparse connectivity.

There are primarily two ways that networks can evolve, both of which can occur simultaneously. The first is that network topology can be changed by the addition or subtraction of nodes (genes) or parts of the network (modules) may be expressed in different contexts. The Drosophila Hippo signaling pathway provides a good example. The Hippo signaling pathway controls both mitotic growth and post-mitotic cellular differentiation. Recently it was found that the network the Hippo signaling pathway operates in differs between these two functions which in turn changes the behavior of the Hippo signaling pathway. This suggests that the Hippo signaling pathway operates as a conserved regulatory module that can be used for multiple functions depending on context. Thus, changing network topology can allow a conserved module to serve multiple functions and alter the final output of the network. The second way networks can evolve is by changing the strength of interactions between nodes, such as how strongly a transcription factor may bind to a cis-regulatory element. Such variation in strength of network edges has been shown to underlie between species variation in vulva cell fate patterning of Caenorhabditis worms.

Local feature

Feed-forward loop

 

Another widely cited characteristic of gene regulatory network is their abundance of certain repetitive sub-networks known as network motifs. Network motifs can be regarded as repetitive topological patterns when dividing a big network into small blocks. Previous analysis found several types of motifs that appeared more often in gene regulatory networks than in randomly generated networks. As an example, one such motif is called feed-forward loops, which consist three nodes. This motif is the most abundant among all possible motifs made up of three nodes, as is shown in the gene regulatory networks of fly, nematode, and human.

The enriched motifs have been proposed to follow convergent evolution, suggesting they are "optimal designs" for certain regulatory purposes. For example, modeling shows that feed-forward loops are able to coordinate the change in node A (in terms of concentration and activity) and the expression dynamics of node C, creating different input-output behaviors. The galactose utilization system of E. coli contains a feed-forward loop which accelerates the activation of galactose utilization operon galETK, potentially facilitating the metabolic transition to galactose when glucose is depleted. The feed-forward loop in the arabinose utilization systems of E.coli delays the activation of arabinose catabolism operon and transporters, potentially avoiding unnecessary metabolic transition due to temporary fluctuations in upstream signaling pathways. Similarly in the Wnt signaling pathway of Xenopus, the feed-forward loop acts as a fold-change detector that responses to the fold change, rather than the absolute change, in the level of β-catenin, potentially increasing the resistance to fluctuations in β-catenin levels. Following the convergent evolution hypothesis, the enrichment of feed-forward loops would be an adaptation for fast response and noise resistance. A recent research found that yeast grown in an environment of constant glucose developed mutations in glucose signaling pathways and growth regulation pathway, suggesting regulatory components responding to environmental changes are dispensable under constant environment.

On the other hand, some researchers hypothesize that the enrichment of network motifs is non-adaptive. In other words, gene regulatory networks can evolve to a similar structure without the specific selection on the proposed input-output behavior. Support for this hypothesis often comes from computational simulations. For example, fluctuations in the abundance of feed-forward loops in a model that simulates the evolution of gene regulatory networks by randomly rewiring nodes may suggest that the enrichment of feed-forward loops is a side-effect of evolution. In another model of gene regulator networks evolution, the ratio of the frequencies of gene duplication and gene deletion show great influence on network topology: certain ratios lead to the enrichment of feed-forward loops and create networks that show features of hierarchical scale free networks.

Bacterial regulatory networks

Regulatory networks allow bacteria to adapt to almost every environmental niche on earth. A network of interactions among diverse types of molecules including DNA, RNA, proteins and metabolites, is utilised by the bacteria to achieve regulation of gene expression. In bacteria, the principal function of regulatory networks is to control the response to environmental changes, for example nutritional status and environmental stress. A complex organization of networks permits the microorganism to coordinate and integrate multiple environmental signals.

Modeling

Coupled ordinary differential equations

For an example of modelling of the cell cycle with ODEs, see cellular model.

 

It is common to model such a network with a set of coupled ordinary differential equations (ODEs) or SDEs, describing the reaction kinetics of the constituent parts. Suppose that our regulatory network has ${\displaystyle N}$ nodes, and let ${\displaystyle S_{1}(t),S_{2}(t),\ldots ,S_{N}(t)}$ represent the concentrations of the ${\displaystyle N}$ corresponding substances at time ${\displaystyle t}$. Then the temporal evolution of the system can be described approximately by

${\displaystyle {\frac {dS_{j}}{dt}}=f_{j}\left(S_{1},S_{2},\ldots ,S_{N}\right)}$

where the functions ${\displaystyle f_{j}}$ express the dependence of ${\displaystyle S_{j}}$ on the concentrations of other substances present in the cell. The functions ${\displaystyle f_{j}}$ are ultimately derived from basic principles of chemical kinetics or simple expressions derived from these e.g. Michaelis-Menten enzymatic kinetics. Hence, the functional forms of the ${\displaystyle f_{j}}$ are usually chosen as low-order polynomials or Hill functions that serve as an ansatz for the real molecular dynamics. Such models are then studied using the mathematics of nonlinear dynamics. System-specific information, like reaction rate constants and sensitivities, are encoded as constant parameters.

By solving for the fixed point of the system:

${\displaystyle {\frac {dS_{j}}{dt}}=0}$

for all ${\displaystyle j}$, one obtains (possibly several) concentration profiles of proteins and mRNAs that are theoretically sustainable (though not necessarily stable). Steady states of kinetic equations thus correspond to potential cell types, and oscillatory solutions to the above equation to naturally cyclic cell types. Mathematical stability of these attractors can usually be characterized by the sign of higher derivatives at critical points, and then correspond to biochemical stability of the concentration profile. Critical points and bifurcations in the equations correspond to critical cell states in which small state or parameter perturbations could switch the system between one of several stable differentiation fates. Trajectories correspond to the unfolding of biological pathways and transients of the equations to short-term biological events. For a more mathematical discussion, see the articles on non-linearity, dynamical systems, bifurcation theory, and chaos theory.

Boolean network

The following example illustrates how a Boolean network can model a GRN together with its gene products (the outputs) and the substances from the environment that affect it (the inputs). Stuart Kauffman was among the first biologists to use the metaphor of Boolean networks to model genetic regulatory networks.

• Each gene, each input, and each output is represented by a node in a directed graph in which there is an arrow from one node to another if and only if there is a causal link between the two nodes.
• Each node in the graph can be in one of two states: on or off.
• For a gene, "on" corresponds to the gene being expressed; for inputs and outputs, "off" corresponds to the substance being present.
• Time is viewed as proceeding in discrete steps. At each step, the new state of a node is a Boolean function of the prior states of the nodes with arrows pointing towards it.

The validity of the model can be tested by comparing simulation results with time series observations. A partial validation of a Boolean network model can also come from testing the predicted existence of a yet unknown regulatory connection between two particular transcription factors that each are nodes of the model.

Continuous networks

Continuous network models of GRNs are an extension of the boolean networks described above. Nodes still represent genes and connections between them regulatory influences on gene expression. Genes in biological systems display a continuous range of activity levels and it has been argued that using a continuous representation captures several properties of gene regulatory networks not present in the Boolean model. Formally most of these approaches are similar to an artificial neural network, as inputs to a node are summed up and the result serves as input to a sigmoid function, e.g., but proteins do often control gene expression in a synergistic, i.e. non-linear, way. However, there is now a continuous network model that allows grouping of inputs to a node thus realizing another level of regulation. This model is formally closer to a higher order recurrent neural network. The same model has also been used to mimic the evolution of cellular differentiation and even multicellular morphogenesis.

Stochastic gene networks

Recent (as of 2007) experimental results have demonstrated that gene expression is a stochastic process. Thus, many authors are now using the stochastic formalism, after the work by Arkin et al. Works on single gene expression and small synthetic genetic networks, such as the genetic toggle switch of Tim Gardner and Jim Collins, provided additional experimental data on the phenotypic variability and the stochastic nature of gene expression. The first versions of stochastic models of gene expression involved only instantaneous reactions and were driven by the Gillespie algorithm.

Since some processes, such as gene transcription, involve many reactions and could not be correctly modeled as an instantaneous reaction in a single step, it was proposed to model these reactions as single step multiple delayed reactions in order to account for the time it takes for the entire process to be complete.

From here, a set of reactions were proposed that allow generating GRNs. These are then simulated using a modified version of the Gillespie algorithm, that can simulate multiple time delayed reactions (chemical reactions where each of the products is provided a time delay that determines when will it be released in the system as a "finished product"). 

For example, basic transcription of a gene can be represented by the following single-step reaction (RNAP is the RNA polymerase, RBS is the RNA ribosome binding site, and Pro _i is the promoter region of gene i):

${\displaystyle {\text{RNAP}}+{\text{Pro}}_{i}{\overset {k_{i,bas}}{\longrightarrow }}{\text{Pro}}_{i}(\tau _{i}^{1})+{\text{RBS}}_{i}(\tau _{i}^{1})+{\text{RNAP}}(\tau _{i}^{2})}$

Furthermore, there seems to be a trade-off between the noise in gene expression, the speed with which genes can switch, and the metabolic cost associated their functioning. More specifically, for any given level of metabolic cost, there is an optimal trade-off between noise and processing speed and increasing the metabolic cost leads to better speed-noise trade-offs.

A recent work proposed a simulator (SGNSim, Stochastic Gene Networks Simulator), that can model GRNs where transcription and translation are modeled as multiple time delayed events and its dynamics is driven by a stochastic simulation algorithm (SSA) able to deal with multiple time delayed events. The time delays can be drawn from several distributions and the reaction rates from complex functions or from physical parameters. SGNSim can generate ensembles of GRNs within a set of user-defined parameters, such as topology. It can also be used to model specific GRNs and systems of chemical reactions. Genetic perturbations such as gene deletions, gene over-expression, insertions, frame shift mutations can also be modeled as well. 

The GRN is created from a graph with the desired topology, imposing in-degree and out-degree distributions. Gene promoter activities are affected by other genes expression products that act as inputs, in the form of monomers or combined into multimers and set as direct or indirect. Next, each direct input is assigned to an operator site and different transcription factors can be allowed, or not, to compete for the same operator site, while indirect inputs are given a target. Finally, a function is assigned to each gene, defining the gene's response to a combination of transcription factors (promoter state). The transfer functions (that is, how genes respond to a combination of inputs) can be assigned to each combination of promoter states as desired.

In other recent work, multiscale models of gene regulatory networks have been developed that focus on synthetic biology applications. Simulations have been used that model all biomolecular interactions in transcription, translation, regulation, and induction of gene regulatory networks, guiding the design of synthetic systems.

Prediction

Other work has focused on predicting the gene expression levels in a gene regulatory network. The approaches used to model gene regulatory networks have been constrained to be interpretable and, as a result, are generally simplified versions of the network. For example, Boolean networks have been used due to their simplicity and ability to handle noisy data but lose data information by having a binary representation of the genes. Also, artificial neural networks omit using a hidden layer so that they can be interpreted, losing the ability to model higher order correlations in the data. Using a model that is not constrained to be interpretable, a more accurate model can be produced. Being able to predict gene expressions more accurately provides a way to explore how drugs affect a system of genes as well as for finding which genes are interrelated in a process. This has been encouraged by the DREAM competition which promotes a competition for the best prediction algorithms. Some other recent work has used artificial neural networks with a hidden layer.