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Seeing the complete
repertoire of genes in a genome confronts us with the fact that we know the
biochemical activities and the biological functions of only a tiny fraction of
the genes and proteins that make up a living organism. The discovery of this
genetic "terra incognita" has reminded us how much of the living world
is beyond the frontier, and challenged us to explore this new world. The torrent of DNA
sequences has not only made a new era of exploration imperative, but also made
it possible: Nucleic acid hybridization provides a simple, direct, way to use
the DNA sequence of a gene as a specific assay reagent to detect and monitor
that gene and its activity. We have therefore developed a convenient tool, a
"DNA microarray", that uses nucleic acid hybridization to monitor
thousands of genes at once. Patrick O. Brown, Research, Dept. of
Biochemistry, Stanford Univ.
There is still a great deal of volatility in the area of microarray
terminology. See FAQ question #
3 for a methodology for investigating and quantitating use of various terms.
Note that names and definitions for arrays - chips- and/or microarrays vary widely in the
literature and are far from standard yet.
Technologies
term index
Sub-categories are Microarrays
categories
Other related glossaries include
Applications Molecular Medicine
Drug discovery &
development Pharmacogenomics
Informatics Algorithms,
Bioinformatics Genomic
Informatics
Technologies Labels, Signaling &
Detection,
Gene
Amplification & PCR; Nanoscience
& Miniaturization
Protein
arrays/microarrays are in the Protein
technologies Cell and tissue arrays are in Cell
& Tissue Technologies
Biology
Expression, SNPs
& genetic
variations
applications - microarrays: See Expression
gene expression analysis
disease classification;
Sequencing genotyping, diagnosis,
drug efficacy and toxicity, sequencing
- mutation detection.
array technology: See microarray.
“Array technology”
in a broader context may refer to computer science, engineering and/ or
telecommunications.
Array technologies include 2D gel electrophoresis,
CCDs Charged Coupled Devices, CCD cameras, detection technologies, fiber optics. imaging,
ink jetting, mass spectrometry,
photolithography, phosphorimagers, piezoelectric, semiconductors, spotting
robots.
arrayed library:
Individual primary recombinant clones (hosted
in phage, cosmid, YAC, or other vector) that are placed in two-
dimensional
arrays in microtiter dishes. Each primary clone can be identified by the
identity of the plate and the clone location (row and column) on that plate.
Arrayed libraries of clones can be used for many applications, including
screening for a specific gene or genomic region of interest … Information
gathered on individual clones from various genetic linkage and physical
map analyses is entered into a relational database and used to construct
physical and genetic linkage maps simultaneously; clone identifiers
serve to interrelate the multilevel maps. [DOE]
Broader terms: Cell biology library, genomic
library; Drug discovery & development
bioassays: Assays & screening
See second definition
blotting:
A technique used for transferring DNA, RNA, or protein
from gels to a suitable binding matrix, such as nitrocellulose or nylon
paper, while maintaining the same physical separation. [IUPAC Biotech] Narrower
terms: Northern
blotting, Southern blotting, Western blotting.
clones: Cell biology
Related term: arrayed library.
competitive hybridization: Gene
Amplification & PCR
cross hybridization:
One of the challenges in measuring mRNA levels on
microarrays is that genes can cross- hybridize, depending on whether the probes
target unique or common regions. [George Church Lab, "S.
cerevisiae cross- hybridization and unique regions", Harvard Medical
School, 1999] http://arep.med.harvard.edu/labgc/adnan/projects/YeastCrossHyb/
Incorrect hybridization that occurs in microarray
experiments by virtue of the fact that the number of incorrect molecules in a target
is so much greater than the number of correct ones. This phenomenon adds a
small amount of noise to every measurement. Cross-hybridization is more of a problem with cDNA arrays than with oligonucleotide
arrays. Related terms: Gene
Amplification & PCR
density of microarrays: The entire yeast genome (6,000+ genes) has been put on a chip. See proteome
chip. Narrower terms: high density oligonucleotide arrays, high density protein arrays, macroarrays, ultra high density.
Related
terms: Expression
deprotection:
During
the chemical synthesis of DNA and RNA, branching is prevented by ensuring that
only one chemically reactive group is present in the growing oligonucleotide and
one in the nucleoside 3′-phosphoramidite. This is achieved by blocking
other reactive groups within the sugars and bases (e.g. exocyclic amines) with
protecting groups. The removal of the protecting groups that block exocyclic
amines, commonly known as deprotection, occurs only after synthesis.
Assessing incomplete deprotection of microarray oligonucleotides in situ,
Holly K. Dressman, Lise Barley-Maloney,1 Laura-Leigh Rowlette, Paul
F. Agris,1* and Mariano A. Garcia-Blanco2 Nucleic Acids
Research v.34(19); Nov 2006
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 genotype multiple
regions of a genome. Each DNA spot contains picomoles (10−12 moles)
of a specific DNA sequence, known as probes (or reporters or oligos).
These can be a short section of a gene or
other DNA element that are used to hybridize a cDNA or
cRNA (also called anti-sense RNA) sample (called target)
under high-stringency conditions. Probe-target hybridization is usually
detected and quantified by detection of fluorophore-,
silver-, or chemiluminescence-labeled
targets to determine relative abundance of nucleic acid sequences in the
target. Wikipedia accessed 2018 Feb 16
https://en.wikipedia.org/wiki/DNA_microarray
DNA Microarray
glossary, Wikipedia
https://en.wikipedia.org/wiki/DNA_microarray#Glossary
FDA draft guidelines - multiplex tests:
Regulatory Affairs
Primarily considers nucleic acid arrays,
but principles apply to protein arrays and tissue arrays.
Related term: analyte specific reagent
fluorescence scanners:
A fluorescence- based detection method used
with microarrays, high- density oligonucleotide arrays, and microelectronic
chips. Fluorescence is generally detected with a confocal scanning
microscope. Related terms:
Imaging Labels
signaling &
Detection
ink jetting technologies:
The most advanced of these [‘drop- on-
demand’ delivery]
approaches are adaptations of the ink- jetting technologies, which utilize
piezoelectric and other forms of propulsion to transfer biochemical substances
from miniature nozzles to solid surfaces. .. [these] allow high- density
gridding of virtually any biomolecule of interest, including cDNAs, genomic
DNAs, antibodies and
small molecules … not currently as robust as photolithography
or microspotting, this approach has been used to prepare microarrays of
single cDNAs at a density of 10,000 spots cm-2. Because ink jetting does
not require direct surface contact, piezoelectric delivery is theoretically
amenable to very high throughput. Mark Schena et al “Microarrays: biotechnology’s
discovery platform for functional genomics” Trends in Biotechnology 16(7):
301- 306
July 1998 See also note under probes- microarrays
lab-on-a-chip LOC:
a device that integrates one or several laboratory functions
on a single integrated
circuit (commonly
called a "chip") of only millimeters to a few square centimeters to
achieve automation and high-throughput screening.[1] LOCs
can handle extremely small fluid volumes down to less than pico liters.
Lab-on-a-chip devices are a subset of micro-electro-mechanical
systems (MEMS)
devices and sometimes called "micro total analysis systems" (µTAS). LOCs
may use microfluidics,
the physics, manipulation and study of minute amounts of fluids. However,
strictly regarded "lab-on-a-chip" indicates generally the scaling of
single or multiple lab processes down to chip-format, whereas "µTAS" is
dedicated to the integration of the total sequence of lab processes to
perform chemical analysis. The term "lab-on-a-chip" was introduced when it
turned out that µTAS technologies were applicable for more than only
analysis purposes. Wikipedia accessed 2018 Feb 16
https://en.wikipedia.org/wiki/Lab-on-a-chip
Lab-On-A-Chip Devices:
Microdevices that combine microfluidics technology with electrical
and/or mechanical functions for analyzing very small fluid volumes. They
consist of microchannels etched into substrates made of silicon, glass, or
polymer using processes similar to photolithography. The test fluids in
the channels can then interact with different elements such as electrodes,
photodetectors, chemical sensors, pumps, and valves. MeSH 2010
mask:
Device which acts as a barrier to the passage of a reagent
(often light - see photolithography). A pattern of holes in
the mask allows selective passage of reagent and results in a corresponding
pattern of reagent deposition or photodeprotection on a surface placed
behind the mask. This allows the generation of spatially addressable libraries.
[IUPAC Combinatorial Chemistry]
matrix:
1) From the Latin word for womb (in turn from mater or mother), a matrix is either the intercellular substance of a tissue, the material in which a fossil is embedded, or a mold from which a relief surface is made in printing or phonograph manufacturing. 2) In mathematics and computer science, a matrix is a set of numbers laid out in tabular form (in rows and columns). From this meaning, a less formal meaning is derived of a complex of lines intersecting at right angles.
[whatis.com] Related term: substrates.
measurement error:
Has two components: variance and bias.
Variance results from uncontrolled (or uncontrollable) variation that
occurs in biological samples, experimental procedures, and arrays themselves.
These factors cause measurements of expression level to vary in an apparently
random fashion between replicas. Bias is a systematic error that causes
the measurement to differ from the correct value. Since bias is systematic, it
affects all replicas the same way.
microarray
technology: A developing technology
used to study the expression of many genes at once. It involves placing
thousands of gene sequences in known locations on a glass slide called a gene
chip. A sample containing DNA or RNA is placed in contact with the gene chip.
Complementary base pairing between the sample and the gene sequences on the chip
produces light that is measured. Areas on the chip producing light identify
genes that are expressed in the sample. NHGRI Glossary
microarrays:
I will keep this term for DNA arrays [regardless of the support] in
which the spacing between spots is less than 500 um. This translates into
densities of at least 400 genes per cm2. S Granjeaud "Expression
profiling: DNA arrays in many guises" BioEssays 21: 781-790 Sept. 1999
A microscopic, ordered array of nucleic acids, proteins, small
molecules, cells or other substances that enables parallel analysis
of complex biochemical samples. Mark Schena et al. "Quantitative monitoring
of gene expression patterns with a complementary DNA microarray" Science
270, 467-470 Oct. 20 1995
The term microarray originally referred to spotted
cDNA arrays, but now we and others use it for any hybridization- based array.
[When the term microarray was first introduced, the prefix micro
served to distinguish this new generation of arrays from their predecessors,
which came to be called macroarrays. Traditionally, microarrays
differ from macroarrays based on the physical size of the surface and the
spots.
Microarrays were developed in large part by Patrick O.
Brown and colleagues at Stanford University. The major characteristics of
microarrays - under the strictest definition of this term - are that they have a
glass or plastic slide as a matrix, use fluorescent dye labeling for the
detection of hybridization, and are created with robots that deposit probes on
the slides. Microarrays also tend to have a large number and high density of
probes; however, their probe density is less than that of high- density
oligonucleotide arrays. The probes used on these arrays can be made from
clones, PCR amplicons, or oligonucleotides. The market for
DNA microarrays has grown significantly since its inception in the mid- 1990s.
New players have entered the market in recent years, driving improvements in
product quality and a search for new market opportunities. The prospect of
participation in the $20 billion in vitro diagnostics industry serves as a
further incentive to current and emerging industry players, creating a fiercely
competitive environment. Narrower terms: Microarrays- categories
Related terms: density of microarrays
microarrays:
Microarrays categories Narrower terms
include antibody microarrays, bead arrays, biochips, bioelectronic
arrays, boutique arrays, cDNA arrays microarrays, CGH arrays, chips,
chromatin array, DNA arrays, DNA chips microarrays, DNA microchip, exon
arrays, filter arrays, gene arrays microarrays, genome arrays, genome
chips, genomic microarrays , glycochips, GPCR microarrays, high density
oligonucleotide arrays, hybridization arrays, in situ arrays, in situ
synthesis, lab- on- a- chip, macroarrays, microarrays, microchip ….,o
microelectronic arrays, microfluidic based chips, multiplex DNA
hybridization arrays, nylon microarrays, oligo arrays, oligonucleotide
arrays, planar arrays, protein arrays, protein biochips, proteome chip,
reverse microarrays, RNA biochip, small molecule microarrays, SNP chips,
spotted arrays microarrays substrate chips, suspension arrays, synthetic
DNA arrays, theme arrays, theme arrays, tiling arrays, transcript arrays,
ultra-high density macroarrays universal arrays, universal microarrays,
whole genome oligonucleotide arrays ;
Expression gene expression
arrays; Related terms include arrayed library. See also arrays, chips.
micron:
One one thousandth of a millimeter; 10,000 angstroms.
[NIGMS] Represented by u.
microspotting:
An original version of mechanical microspotting
was developed by [Dari] Shalon and [Pat] Brown [at Stanford] and later
commercialized at Synteni [now Incyte Genomics] …a miniaturized version
of earlier DNA spotting techniques, encompasses a family of related deposition
technologies that enable automated microarray production by printing small
quantities of premade biochemical substances onto solid surfaces. Printing
is accomplished by direct surface contact between the printing substrate
and a delivery mechanism that contains an array of tweezers, pins or capillaries
that serve to transfer the biochemical samples to the surface. M Schena
et al “Microarrays: biotechnology’s discovery platform for functional genomics”
Trends in Biotechnology 16(7): 301- 306 July 1998 Related terms: Stokes shift, spotted arrays, spotting robots.
microwell chips: Narrower term: nanowells
Northern blotting:
Detection of RNA that has been electrophoretically
separated and immobilized by blotting on nitrocellulose or other type of paper
or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
MeSH, 1991
organ-on-a-chip (OOC):
Cell and tissue technologies phosphorimagers:
Instruments used to quantify the radioactive signal
(an indication of the level of hybridization) produced by macroarrays.
photolithography:
Process by which selective masking generates
light patterns which direct chemical transformations to certain areas of
a photosensitive surface. Coupling of different building blocks to discrete
sites may give rise to spatially addressable arrays of compounds. [IUPAC
Combinatorial Chemistry]
Unlike droplet- printing technology, which allows microarrays to be created
with relatively inexpensive and user- friendly equipment, photolithography
requires expensive equipment and particular expertise and is also protected by
patents. Related term: soft lithography
printing:
The placing of probes on an array - a
process often called printing - is accomplished by automated machinery
that can produce very small spots and place them quite close to one another with
high precision. With modern equipment, spot diameters are in the range of 100 mm, and it is possible to place 10,000- 30,000 probes on a standard 1" x
3" glass slide. The large number of probes is a bit misleading in that it
is often necessary to represent each gene by two different probes to achieve
adequate reproducibility. Thus, an array with 30,000 probes might represent only
15,000 genes.
probes - microarray:
In this paper "probe" refers to the (labeled) material that is hybridised
with the array of cDNA inserts or oligonucleotides ("targets"). The oligonucleotide
chip community tends to use the reverse terminology. S Granjeaud "Expression
profiling: DNA arrays in many guises" BioEssays 21: 781-790, Sept. 1999
We use the term probe for the DNA affixed to the array, and target
for the DNA or RNA being hybridized to the array. This usage is fairly common,
although some authors reverse the meanings of probe and target. CHI Microarray
Informatics report
Two technologies are available for placing the DNA probes on the array.
The traditional and most popular approach involves contact spotting, in which
the DNA is loaded into a print tip and deposited by physically tapping the tip
on the surface. There is also a newer noncontact method in which DNA is sprayed
onto the surface using technology adapted from computer ink- jet printers.
[The ink- jet method is sometimes called indirect because
the DNA is sprayed onto the surface rather than being directly placed.] The ink-
jet method is capable of producing smaller spots, and because it avoids physical
contact with the surface may prove to be more reliable. (The physical contact
can introduce more variability into spots.) Can be made from clones, PCR
amplicons
or oligonucleotides. See also probes Gene
amplification & PCR
protein arrays, protein chips, protein
microarrays: Protein technologies
RNA expression arrays: Expression
sample:
In microarray work, this term often refers
to the biological material from which mRNA is extracted (e.g., tissue or serum
from patients or laboratory animals). However, sample is also an
important term in statistics, where it means the subset of a population that is
surveyed for the purpose of estimating properties of the entire population. See also Drug
discovery & developmen sample
scanning technologies: See fluorescent scanners, laser scanning phosphorimagers Related term: image analysis - microarrays
See also Imaging, Mass Spectrometry
solution arrays: Labels, signaling & detection
Southern blotting:
A method (first developed by E.M. Southern)
for detection of DNA that has been electrophoretically separated and immobilized
by blotting on nitrocellulose or other type of paper or nylon membrane. MeSH,
1989
The Southern blot was the first array.
Eric Lander "Array of hope" Nature Genetics 21 (1s): 3-4 Jan 1999
spots:
Parts of the image corresponding
to the DNA probes on the microarray.
spotting robots:
Most spotting robots use an X-Y-Z robot arm (one that
can move in three dimensions) mounted on an antivibration table. Pins held by
the arm are dipped into the first microtiter plate to pick up the fluid (probe
solution) to be delivered. The tips of the pins are then moved to the array
matrix and allowed to touch the surface only minimally; the probe solution is
then transferred. The pins are then washed and moved to the next set of wells
and probes. This process is repeated until hundreds or thousands of probes are
deposited. Currently, solid pins, quills, and pin- and- ring configurations of
pins are available. Related terms: Stokes shift, microspotting, spotted arrays.
Stokes shift:
The difference (usually in frequency units) between the spectral positions of the band
maxima (or the band origin) of the absorption and luminescence arising from the same electronic
transition. Generally, the luminescence occurring at a longer wavelength than the absorption
is
stronger than the opposite. The latter may be called an anti- Stokes shift.
[IUPAC Photo] Related terms: microspotting, spotted arrays,
spotting robots.
substrates:
In
hybridization arrays, the particular materials onto which probes are deposited.
Substrate materials include glass, nylon, silicon, and ceramic. Traditionally,
arrays have been prepared using plastic multiwell plates. As the need for more
reaction "vessels" per unit area has increased dramatically, users
have turned to flatter supports such as glass slides, which provide greater
surface areas. Different from substrate Pharmaceutical
biology Related term: matrix
Western blotting:
Identification of proteins or peptides that
have been electrophoretically separated by blotting and transferred to
strips of nitrocellulose paper. The blots are then detected by radiolabeled
antibody probes MeSH, 1989
Microarrays resources
MGuide, [Pat] Brown Lab’s Guide to Microarraying, Stanford Univ., US
http://cmgm.stanford.edu/pbrown/mguide/
How
to look for other unfamiliar terms
IUPAC definitions are
reprinted with the permission of the International Union of Pure and Applied
Chemistry.
I have tried to determine the status of all words known to be, or
are suspected of being, proprietary names or trademarks and to include
this information. No judgment concerning the legal status of such words
is claimed.
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