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Microarray
technologies have become an invaluable tool for drug discovery as well as for
diagnostics. Microarrays are being used to find new drug targets as well as
developing personalized medicine in a fast and affordable manner. However, many
challenges of the technology remain -- quality control, expression arrays
and pharmacokinetics will be addressed as well as new developments in the field,
such as microRNA arrays and DNA methylation. Microarrays
in Medicine: Optimizing Diagnostics and Therapeutics, May 19-20 2008, Boston MA
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
map Finding guide to terms in these glossaries Site
Map
Sub-categories are Microarrays
categories
Other related glossaries include
Applications Molecular Medicine
Drug discovery &
development Pharmacogenomics
Informatics Algorithms,
Bioinformatics
Technologies Labels, Signaling &
Detection,
Gene
Amplification & PCR; Nanoscience
& Miniaturization
Biology
Expression, SNPs
& genetic
variations
analyte
specific reagents: Drug approvals
glossary
antibody microarrays: Microarrays
categories Related terms: protein arrays
applications - microarrays: See Expression
glossary gene expression analysis disease classification;
Sequencing glossary 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 glossary library, genomic
library; Drug discovery & development
glossary
arrays: Microarrays categories
Narrower terms include bead arrays, bead based arrays,
bioarrays, bioelectronic arrays, cDNA arrays, cell arrays, DNA arrays, encoded
bead arrays, gel pad arrays, gene arrays, gene expression arrays, genome arrays,
genomic arrays,
high density oligonucleotide arrays, high density protein arrays, hybridization arrays,
in situ arrays, low density arrays, microelectronic arrays, multiplex DNA hybridization arrays,
nanoarrays, nylon macroarrays, oligo arrays, oligonucleotide
arrays, oligosaccharide arrays, peptide arrays, planar arrays, protein arrays, solution arrays, spotted arrays,
tissue arrays, exon
arrays, filter arrays, macroarrays, small molecule microarrays, suspension arrays,
theme arrays, tiling arrays, transcript arrays; Expression
glossary gene expression arrays; Related terms include arrayed library.
See also chips, microarrays.
BAC microarrays,
bead arrays, bead
based arrays, bioarrays: Microarrays categories
bioassays: Assays & screening
glossary
See second definition
biochip(s): Microarrays categories
bioelectronic arrays: See Microarrays
categories under microelectronic arrays
biofabrication: Biomaterials
& bioengineering glossary
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. cDNA arrays:
Microarrays categories
CCD Charged Coupled Device: Molecular
Imaging
glossary
cell arrays, cell microarrays;
cell chips, CellChip™
System; chemical microarrays: Microarrays
categories
chips: Microarrays categories
classification- microarrays: Algorithms
glossary
clones: Cell biology glossary
Related term: arrayed library. cluster analysis: Algorithms
glossary Narrower term: k- means clustering.
competitive hybridization: Gene
Amplification & PCR
concordance: Similarity
of results between different microarray platforms.
Related terms: discordance, mismatches
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
DNA arrays, DNA chips, DNA
microarrays, DNA microchips: Microarrays
categories
DNA microarray:
Wikipedia http://en.wikipedia.org/wiki/DNA_microarray
data analysis - microarrays:
Microarrays have revolutionized molecular biology. The
numbers of applications for microarrays are growing as quickly as their probe
density. Paradoxically, microarray data still contains a large number of
variables and a small number of replicates creating unique data analysis sets.
Still, the first and most important goal is to design microarray experiments
that yield statistically defensible results.. Microarray
Data Analysis and Interpretation, Aug. 16-17, 2007, Washington DC
It is obvious to
reviewers of submitted manuscripts that many researchers have used microarrays
to perform experiments that provide no biological insight whatsoever. That's not
due to any failure on the part of the technology, but rather on the failure to
design experiments or appreciate the limitations of microarray technology. The
use of microarrays will not turn a poorly conceived or poorly executed
experiment into a groundbreaking scientific achievement, any more than buying a
sports car will turn one into a NASCAR driver. Catherine Ball, Director Stanford
Microarray Database as part of a panel on Has the Promise of Microarrays been
oversold? Science Functional Genomics weblog http://sciencemag.blogs.com/sfgblog/roundtable/
Terry Speed's Microarray Data Analysis Group Page, UC-
Berkeley, US http://www.stat.Berkeley.EDU/users/terry/zarray/Html/index.html
Related terms: image analysis - microarrays; standards; cluster analysis,
pattern recognition Algorithms & data
management glossary
data mining tools: See under data analysis - microarrays.
dendrimer: Nanoscience
& Miniaturization
glossary
density of microarrays:
Low (200-5000 genes): low-density arrays (Clontech, Research Genetics) —Medium: microarrays (14,000
cDNAs/ array; Agilent), spotted oligos (8000; Clontech) —High (>10,000 genes): high- density oligo arrays
(Affymetrix) CHI,
GenomeLink 14.1, 2001 http://www.healthtech.com/newsarticles/issue14_1.asp
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 glossary
derived bioassay: See under bioassay
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 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1636491 detection
technologies: Labels, signaling & detection glossary
disconcordance: Lack
of standard results among microarray experiments.
Related terms: concordance, mismatches
electrospray- fabricated protein microarrays: Microarrays
categories
encoded bead arrays: See under Microarrays
categories bead arrays
exon arrays: Microarrays categories
External RNA
Control Consortium ERCC: http://www.cstl.nist.gov/biotech/workshops/ERCC2003/
FDA draft guidelines - multiplex tests: Drug
and device approvals glossary
Primarily considers nucleic acid arrays,
but principles apply to protein arrays and tissue arrays.
Related term: analyte specific reagent
FDA
-- microarrays - regulating:
The Food and Drug Administration (FDA) must balance the interests of the public for thorough review of new products for safety and efficacy, against the interests of the industry for a low cost, expedited process of regulatory approval. But all too often the process can place a significant drain on the resources of a company, particularly smaller companies that are introducing new products or innovative technology. It is actually in the interest of all parties to meet each of these requirements. Patients also have an interest in expedited review of new drugs, devices and diagnostics. Companies welcome a regulatory regime that ensures safety and thus public confidence in their products. And it is in nobody’s interest to have a company bankrupt itself just as it is trying to bring an innovative drug or technology to market. The FDA, however, is faced with extraordinary challenges, not only in terms of increased workload of conventional products, but also in trying to
re- define regulatory procedures that are appropriate for technologies that take an entirely different approach to diagnostics and treatment, including
microarrays, genotyping and pharmacogenomics.
How the genomic revolution affects FDA Regulation, CHI GenomeLink 5.1 http://www.healthtech.com/newsarticles/issue5-1.ASP
false negative:
The chance
of declaring an expression change (e.g., in gene expression) to be insignificant
when in fact a change has occurred. The opposite situation is the false
positive.
false positive: The chance
of declaring an expression change to be significant when in fact no change has
occurred. This tends to be a more pressing concern than false negatives in
microarray experiments.
fiber optics:
Imaging glossary
filter arrays: Microarrays
categories
filtering: A process whose
aim is to reduce a dataset to a more manageable size, by getting rid of genes
that show no significant expression changes across the experiment or that are
uninteresting for biological reasons.
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. [CHI Microarrays
report]
Related terms:
Imaging
glossary
fold change:
A way of
describing now much larger or smaller one number is compared with another. When
the first number is larger than the second, it is simply the ratio of the first
to the second. When the first number is smaller than the second, it is the ratio
of the second to the first with a minus sign in the front. When the numbers are
equal, it is 1. For example, the fold change of 50 versus 10 is 50/10 = 5, while
the fold change of 10 versus 50 is -5.
functional protein microarrays: Microarrays
categories
gel-pad arrays: Microarrays categories
gene arrays, gene microarrays: Microarrays
categories: See also DNA chip, DNA arrays, DNA
microarrays
GeneChip
®; genome arrays: Microarrays categories
gene expression arrays: Expression glossary
Related terms: genome
chip, genomic arrays, genomic microarrays.
genome chip: Microarrays categories
Related terms genome arrays, genome chip, genomic microarrays.
genomic microarrays: Microarrays
categories Related terms genome arrays, genome chip, genomic arrays.
Narrower term:
GenosensorTM system
global normalization
or mean scaling:. The standard solution
for errors that effect entire arrays is to scale the data so that the average
measurement is the same for each array (and each color). The scaling is
accomplished by computing the average expression level for each array,
calculating a scale factor equal to the desired average divided by the actual
average, and multiplying every measurement from the array by that scale factor.
The desired average can be arbitrary, or computed from the average of a group of
arrays.
glycochips: Microarrays categories
Related terms: Glycosciences
glycoinformatics, glycobiology
gridded cDNA microarrays: See Microarrays
categories: cDNA arrays.
high density oligonucleotide arrays: Microarrays
categories Broader terms: oligonucleotide arrays,
oligonucleotide chips, oligonucleotide microarrays,
microchips.
Related term: density of microarrays
high-density protein arrays: Microarrays
categories
hybridization: Gene
amplification & PCR glossary
hybridization arrays: Microarrays
categories Also called hybridization array assays
image
analysis - microarrays: Although the visual image of a microarray panel is alluring, its information
content, per se, is minimal without significant image processing. To mine
its lode effectively, quantitative signal must be determined optimally,
which means subtracting background, calculating confidence intervals -
outside of which a difference in signal ratio is deemed to be significant - and calibrated.
Editorial “Getting hip to the chip” Nature Genetics
18(3): 195- 197 March 1998 This process starts with the image of a microarray
that is produced in the laboratory and produces intensity information indicating
the amount of light emitted by each probe. In particular, after the array has
been hybridized, it is scanned to obtain an image that shows the amount of light
emitted across the surface of the microarray. The image is then analyzed to
identify the "spots" (i.e., the parts of the image corresponding to
the DNA probes on the microarray) and the amount of light that can be attributed
to target molecules bound to each probe.
Related term: normalization
in situ array:
Microarrays
categories
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
LabChipR Microarrays
categories
lab-on-a-chip: Microarrays categories
Related terms: biochip, LabChipR, protein
chip, microelectronic arrays, microfluidics based chips, pump chip,
tissue chip See also chips.
laser, laser scanning: Molecular
Imaging glossary Related
terms: CCD, image analysis, scanning technology.
learning algorithms: Algorithms
glossary
lithography:
Lithography Overview, Intel Research,
US http://www.intel.com/research/silicon/lithography.htm
Narrower terms: photolithography, soft lithography
log ratios: DNA
microarray assays typically compare two biological samples and present the
results of those comparisons gene-by-gene as the logarithm base two of the ratio
of the measured expression levels for the two samples. The limits of log ratios,
Vasily Sharov,1 Ka Yin Kwong,1 Bryan Frank,1
Emily Chen,1 Jeremy Hasseman,1 Renee Gaspard,1
Yan Yu,1 Ivana Yang,1 and John Quackenbush BMC
Biotechnology 4, 2004 doi: 10.1186/1472-6750-4-3. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=400743
low-density arrays: Microarrays
categories See also under density of microarrays. Related term: macroarrays
lymphochip: Microarrays categories
MAGE Microarray
and Gene Expression:
The group aims to provide a standard for the
representation of microarray expression data that would facilitate the exchange
of microarray information between different data systems. http://www.mged.org/Workgroups/MAGE/mage.html
MAGE-ML MicroArray and Gene Expression Markup Language:
A language
designed to describe and communicate information about microarray based
experiments. MAGE-ML is based on XML and can describe microarray designs,
microarray manufacturing information, microarray experiment setup and execution
information, gene expression data and data analysis results. MAGE-ML has been
automatically derived from Microarray Gene Expression Object Model (MAGE-OM),
which is developed and described using the Unified Modelling Language (UML) -- a
standard language for describing object models. [Robin Cover, XML Cover Pages:
Microarray and Gene Expression Markup Language, 2002] http://xml.coverpages.org/mageML.html
Related terms: GEML, MAML, MIAME
MAML Microarray Markup Language:
MAML (Microarray
Markup Language) is no longer supported by MGED and has been replaced by
MAGE-ML. http://www.mged.org/Workgroups/MAGE/mage.html
Broader term: standards;
Related terms: data analysis - microarray, MGED, MIAME
MGED
Microarray Gene Expression Database group:
The MGED group is a grass- roots
movement whose goal is to facilitate the adoption of standards for DNA- array
experiment annotation and data representation, as well as the introduction of
standard experimental controls and data normalization methods. The group was
founded at the Microarray Gene Expression Database meeting MGED1
(November, 1999, Cambridge, UK). There are four major standardization
projects being pursuing by the group:, MIAME, MAGE, Ontologies,
Normalisation. http://www.mged.org/
Broader term: standards;
Related terms: data analysis - microarray,
MAGE, MAML, MIAME.
MIAME
Minimum Information About a Microarray Experiment:
MIAME aims
to outline the minimum information required to unambiguously interpret
microarray data and to subsequently allow independent verification of this data
at a later stage if required. MIAME is not a dogma for microarray
experiments to follow, but just a set of guidelines. This set of guidelines will
then assist with the development of microarray repositories and data analysis
tools. [MIAME homepage 2003] http://www.mged.org/Workgroups/MIAME/miame.html
MIAME Checklist, MGED, 2003 http://www.mged.org/Workgroups/MIAME/miame_checklist.html
MIAME glossary, MGED, MIAME, 2003 http://www.mged.org/Workgroups/MIAME/miame_glossary.html
MIAME software, MGED, 2003 http://www.mged.org/Workgroups/MIAME/miame_software.html
A list of possibly MIAME compliant software
Broader term: standards; Related terms: data analysis - microarray,
MAGE,
MAML, MGED
MIAME/MAGE-OM: The boundaries between MIAME concepts, the MIAME-
compliant MAGE-OM
and the MGED ontology (that try to define and structure the MIAME concepts) is
neither well defined nor easy to understand. In order to provide some help, this
webpage contains explanatory documentation to understand the MIAME concepts, how
its requirements map to the MAGE-OM and where the MGED ontology inclusion is
required. [MGED, MIAME MAGE-OM, 2002] http://www.mged.org/Workgroups/MIAME/miame_mage-om.html
macroarrays: Microarrays categories
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]
mass spectrometry:
This technique can be used to both measure and
analyze the molecules contained in microarray spots. It involves introducing
enough energy into a target molecule to cause its ionization and disintegration.
The resulting fragments are then analyzed, based on the mass/ charge ratio to
produce a "molecular fingerprint. [CHI Microarrays
report]
Mass spectrometry
glossary
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.
measured bioassay: See under Assays
& screening glossary
bioassay
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.
medium density microarrays: See under density of microarrays
MGED Network,
Ontology Working Group: The primary purpose of the
MGED Ontology is to provide standard terms for the annotation of microarray
experiments. These terms will enable structure queries of elements of the
experiments. Furthermore, the terms will also enable unambiguous descriptions of
how the experiment was performed. The terms will be provided in the form of an
ontology which means that the terms will be organized into classes with
properties and will be defined. A standard ontology format will be used. http://mged.sourceforge.net/ontologies/index.php
microarray
informatics: See data analysis - microarrays
microarray technology: Hybridization
based tool used to analyze how large numbers of genes interact with each other
and how a cell's regulatory network controls a vast battery of genes
simultaneously; used for genotyping, mapping, sequencing, sequence detection;
usually constructed by applying biomolecules onto a slide or chip, labeled with
fluorescent probe and scanned with microscope or imaging equipment. CRISP
Thesaurus, NIH, US http://crisp.cit.nih.gov/Thesaurus/00018498.htm
microarrays:
Microarray based technologies have evolved into
a very viable diagnostic tool, due to the reliability of their data, as
recently confirmed by a study published in Nature Biotechnology. Gene
expression results of known quality are key to the successful employment of
microarrays for diagnosis and prognosis of diseases, for predicting the
patient’s response to new or existing therapeutics, or to identify new
diagnostic markers. These are just some of the potentials they offer and such
make them also an exciting tool for therapeutic development. Getting
Optimized Targets: Microarrays
in Medicine April 11-13, 2007 • Boston, MA
Tool for studying how large numbers of genes interact
with each other and how a cell’s regulatory networks control vast batteries
of genes simultaneously. Uses a robot to precisely apply tiny droplets
containing functional DNA to glass slides. Researchers then attach fluorescent
labels to DNA from the cell they are studying. The labeled probes are allowed
to bind to cDNA strands on the slides. The slides are put into a scanning
microscope to measure … how much of a specific DNA fragment is present. NHGRI
glossary http://www.nhgri.nih.gov/DIR/VIP/Glossary/pub_glossary.cgi
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
Stanford MicroArray Database
(SMD), Stanford Univ., US http://genome-www4.stanford.edu/MicroArray/SMD/
Stores raw and normalized data from microarray experiments, as well
as their corresponding image files. In addition, SMD provides interfaces
for data retrieval, analysis and visualization.
Microarray databases: Databases
& software directory
Narrower terms: Microarrays categories
antigen microarrays, chemical microarrays, electrospray fabricated protein microarrays, functional
protein microarrays, genomic microarrays, glycoprotein microarrays, oligonucleotide arrays, protein microarrays,
antibody microarrays,
BAC microarrays, cell
microarrays, DNA microarrays, gene microarrays, gridded
cDNA microarrays, small molecule
microarrays, tissue microarrays. Related terms: arrays, chips, data analysis -
microarrays, density of microarrays, probes - microarrays.
microarray data analysis: See data analysis - microarrays.
microarray informatics:
The microarray field is experiencing an
overwhelming push toward robust statistics and mathematical analytic methods
that go far beyond the simple fold analysis and basic clustering that were once
the mainstays of researchers in this area. This push toward better statistics is
also driving the recognition of the need for more replication of experiments.
These stronger analytical techniques also help researchers identify problem
areas in the technology and laboratory processes, and these improvements, in
turn, greatly improve the quality of results that can be provided.
microarrays- categories:
Numerous types of microarrays are in common
use today, but for our purposes, it suffices to categorize them into three main
groups: spotted cDNA microarrays, spotted oligonucleotide microarrays,
and Affymetrix GeneChips, which are sufficiently unique to warrant their
own grouping. In the spotted- array categories, we include both
traditional arrays produced using contact printing in the style of Pat Brown
(Stanford University), and ones produced using the newer ink- jet
technology pioneered in the laboratory of Lee Hood of the University of Washington and developed
to commercial fruition by Rosetta Inpharmatics and Agilent Technologies.
Current DNA array formats can be categorized
into various groups based on the type of matrix, the probe number and/or density,
the physical size of the array, and the type of target labeling. The general
categories we describe are macroarrays, microarrays, high- density
oligonucleotide arrays (e.g., Affymetrix’s GeneChips), and microelectronic
arrays.
microarrays - regulation:
Drug approvals glossary
microarray technologies: See array technologies.
microchips: Nanoscience & Miniaturization glossary
microelectronic arrays: Microarrays
categories Also called microelectronic chips
See also under multiplex DNA
hybridization arrays
microelectrophoresis chips, microfluidics-based chips: Microarrays
categories
microfluidic devices: Nanoscience
& Miniaturization
glossary
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
mismatches: Gene
expression microarray data is notoriously subject to high signal variability.
Moreover, unavoidable variation in the concentration of transcripts applied to
microarrays may result in poor scaling of the summarized data which can hamper
analytical interpretations. This is especially relevant in a systems biology
context, where systematic biases in the signals of particular genes can have
severe effects on subsequent analyses. Conventionally it would be necessary to
replace the mismatched arrays, but individual time points cannot be rerun and
inserted because of experimental variability. It would therefore be necessary to
repeat the whole time series experiment, which is both impractical and
expensive. Correction of scaling mismatches in oligonucleotide microarray data,
Mrtino Barenco, Jaroslav Stark3 ,1, Daniel Brewer2 ,1,
Daniela Tomescu1, Robin Callard1 ,2 and Michael Hubank1
BMC bioinformatics 2006, 7:251 doi:10.1186/1471-2105-7-251 http://www.biomedcentral.com/1471-2105/7/251
multiplex assays:
Insight
Pharma Report forthcoming 2009
multiplex DNA hybridization arrays: Microarrays
categories
nanoarray: Microarrays
categories
nanochip: Nanoscience &
miniaturization glossary
noise
characterization: Noise is a big problem in analyzing gene expression
microarray data.
normality:
The collection
of log ratios from a single microarray experiment is typically quite unlike a
random sample from a single normal population. This is particularly so when a
lot (say > 10%) of genes are differentially expressed. ..Conclusion.
It is dangerous to use normal statistical theory to guide your selection of
differentially expressed genes. The normal thinking which says that about 68%
should be within 1 standard deviation (SD), 95% within 2 SDs and 99% within 3
SDs of the mean does not apply, even when no
differential expression is present. Avoid assuming normality, Terry Speed
Group Microarray Page, 2000 http://stat-www.berkeley.edu/users/terry/zarray/Html/normality.html
Related term: Clinical
genomics glossary normal
normalization: One approach is to place a modest number of control probes on the array and
add known quantities of matching target molecules to the sample. This is often
called a spike-in method, because the sample is "spiked"
with known quantities of control target. The idea is that by correlating the
readout of each control with the known amount of target, it should be possible
to better account for variations in the process. A nice study of this approach
for Affymetrix GeneChips was done by Gene Brown’s laboratory at Genetics
Institute/ Wyeth- Ayerst Research. Footnote: Hill AA, Brown EL, et al.
"Evaluation of normalization procedures for oligonucleotide array data
based on spiked cRNA controls." Genome Biology. 2001 2(12):
research0055.1-0055.13 ] http://www.genomebiology.com/2001/2/12/research/0055.
There are many sources of systematic variation in
microarray experiments which affect the measured gene expression levels.
Normalization is the term used to describe the process of removing such
variation. ... Such sources of systematic variation include: Differences in
labelling efficiency between the two dyes. Differences in the power of the two
lasers. Differing amounts of RNA labelled between the 2 channels. Spatial biases
in ratios across the surface of the microarray. MGED Normalization Working
Group, 2002 http://www.dnachip.org/mged/normalization.html
The conversion of intensity
information (from image analysis) into estimates of gene expression
levels. For researchers who are using statistical methods, this process also
characterizes the uncertainty in the measurements. The goal of normalization is
to convert the intensity measurements generated by image analysis into estimates
of gene expression levels in the original biological source. Concretely,
the challenge is to compensate for as many sources of error as possible.
Normalization for cDNA microarrays, Yee Hwa Yang, Sandrine
Dudoit, Percy Luu and Terry Speed, 2001 http://www.stat.berkeley.edu/users/terry/zarray/Html/normspie.html
Related terms: fold changes, image analysis, log
ratios; See also normalization: Algorithms glossary
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
nylon macroarrays: Microarrays
categories
oligo arrays, oligo chips: See Microarrays
categories: oligonucleotide arrays, oligonucleotide chips,
oligonucleotide microarrays
oligonucleotide: Biomolecules glossary
oligonucleotide array sequence analysis:
Hybridization of a nucleic acid sample to a very large set of
oligonucleotide probes, which are attached to a solid support, to determine sequence or to detect variations in a gene
sequence or
expression or for gene mapping.
MeSH, 1999
Useful to know this MeSH heading for microarrays, but use free- text as
well to search PubMed.
oligonucleotide arrays, oligonucleotide chips, oligonucleotide
microarrays: Microarrays categories
oligosaccharide arrays: See Microarrays
categories: glycochips.
Ontology Working Group:
Charged with developing an ontology for
describing samples used in microarray experiments. MGED Network, Ontology Working
Group http://mged.sourceforge.net/ontologies/index.php
pattern recognition: Algorithms &
data management glossary
peptide arrays: Microarrays
categories Related terms: protein arrays,
protein chips, protein microarrays
phenotypic microarray: Microarrays
categories Related term: Genomics glossary phenotype
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
physical bioassay: See under Assays
& screening glossary bioassay
piezoelectric:
A material that generates an electric charge when mechanically
deformed. ..[About.com http://chemistry.about.com/library/glossary/bldef700.htm planar arrays: Microarrays categories
primer extension: Gene
amplification & PCR glossary
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
profiling: SEE gene expression
protein array
analysis: Ligand-binding assays that
measure protein- protein, protein- small molecule or protein- nucleic acid
interactions using a very large set of capturing molecules, i.e., those attached
separately on the solid support, to measure the presence or interaction of
target molecules in the sample. MeSH 2003
protein arrays:
Protein arrays are poised to become a central proteomics
technology allowing for the global observation of biochemical activities on an
unprecedented scale. Hundreds or thousands of proteins can be simultaneously
screened for protein-protein, protein-nucleic acid, and small molecule
interactions. The value of multiplexed protein measurement is being established
in applications including: comprehensive proteomic surveys, studies of protein
networks and pathways, validation of genomic discoveries, and clinical biomarker
development. This technology holds great potential for basic molecular biology
research, serum profiling, protein abundance determination, disease biomarker
identification, immune and toxicological response profiling, and pharmaceutical
target screening. Protein
Arrays January 11-12, 2007, San Diego CA
Google = about 1,720 July 10, 2002;
about 6,350 Sept. 16, 2003; about 10,800 Aug. 6, 2004, about 137,000 Oct.
5, 2005; about 176,000 Nov 10, 2006
Related terms: antibody arrays, protein chips, protein microarrays
Narrower
terms: high- density protein arrays, protein-
protein
interaction chips, proteome chip
protein biochips: Microarrays
categories
protein chips:
The protein chip is not going to
replace certain discovery methods (such as 2D gel electrophoresis), which are
very good at identifying novel proteins in a complex mixture. Perhaps the
greatest limitation of methods based on electrophoresis is that they are
relatively expensive to perform in terms of the cost per data point, and can be
quite laborious. The trend, however, may continue toward reduced costs and ease
of use. Another limitation of conventional proteomic methods is that they may
not be versatile enough to rapidly gather biological information - changes in
protein expression, protein- protein
interactions, response to various
conditions.
Ciphergen has trademarked ProteinChip™.
Some chips can operate with both nucleic acids and proteins. Analogous
to DNA chips, these are used for studying
protein expression
or protein- protein interactions.
Google = about 56,400
Oct. 5, 2005; about 92,400 Aug 29, 2007
See also Microarrays categories
Related terms: protein arrays, protein microarrays; Narrower
terms: high- density protein microarrays, protein-protein
interaction chips, proteome chip
protein expression arrays: Expression
glossary protein microarrays:
These arrays can consist of proteins themselves
(e.g., for studies of protein/ protein interactions or protein/ small- molecule
binding) or of probes for capturing proteins (so that protein levels in a sample
can be gauged). [CHI Microarrays
report] More...Microarrays
categories Related
terms: protein arrays, protein chips; Narrower terms: electrospray-
fabricated protein microarrays, functional protein microarrays, protein- protein
interaction chips, proteome chip Wikipedia
http://en.wikipedia.org/wiki/Protein_microarray
proteome
microarray: See Microarrays categories: proteome chip Broader terms:
protein arrays, protein chips, protein microarrays.
pump chip, RNA biochip, RNA chips: Microarrays
categories
RNA expression arrays: Expression
glossary
regulating
microarrays: See FDA -- microarrays - regulating
reverse
transfection: A microarray- based system for the functional analysis in
mammalian cells of many genes in parallel. Mammalian cells are cultured on a
glass slide printed in defined locations with solutions containing different
DNAs. Cells growing on the printed areas take up the DNA, creating spots of
localized transfection within a lawn of non- transfected cells. ... we have developed two methods to reverse
transfect cells.... By printing sets of
complementary DNAs (cDNAs) cloned in expression vectors, we can make microarrays
whose features are groups of live cells that express a defined cDNA at each
location. These 'transfected cell microarrays' should be of broad utility for
the high- throughput expression cloning of genes, particularly in areas such as
signal transduction and drug
discovery. For many applications these arrays can
serve as substitutes for protein microarrays, particularly for proteins that are
difficult to purify, such as membrane proteins. David Sabatini
"Reverse transfection" Whitehead Institute, MIT, US http://staffa.wi.mit.edu/sabatini_public/reverse_transfection/frame.htm Rolling Circle Amplification RCA:
Gene amplification & PCR glossary
Systems Literature
Analysis SLA: Information Management &
Interpretation glossary
SNP chips: Microarrays categories
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 & development glossary sample
scanning technologies: See fluorescent scanners, laser scanning phosphorimagers Related term: image analysis - microarrays
See also Imaging
glossary, Mass Spectrometry
semiconductor : Miniaturization
& nanoscience glossary
small molecule microarrays: Microarrays
categories
soft lithography:
A new technique capable of generating and manufacturing
nano- structures rapidly and economically. Inherent in its nature is the ability to produce patterned three dimensional structures on
non- planar substrates in a single step. An elastomeric polydimethylsiloxane (PDMS) patterning element (mould) is first prepared by casting the liquid
pre- polymer against a previously patterned master and curing. Once cured the patterned PDMS element is removed from the
master ... When a PDMS mould is brought into conformal contact with a solid substrate continuous channels are formed. Micromoulding of patterns on the substrate surface is then made possible by filling these channels with a liquid precursor blend of choice by capillary action. The precursor is then cured and the PDMS element is removed. Since PDMS is transparent to ultra violet radiation and is thermally stable to 150 degrees
Celsius, liquid precursors may be easily cured
in situ to yield the desired patterned structure.
To date at NMRC, this method has been used to pattern organically modified ceramic gels (ORMOCERS), liquid
pre- polymers and aqueous solutions of inorganic salts.
NMRC (Ireland) Nanotechnology Research, Scientific Report 1999 http://www.nmrc.ie/reports/1999/scientific/scinano.html
solution arrays: Labels, signaling & detection glossary
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
spike-in: See under normalization
spots:
Parts of the image corresponding
to the DNA probes on the microarray.
spotted arrays:
See Microarrays
categories: cDNA arrays, microarrays - categories of
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.
standards:
See GEML, MGED, MIAMI 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.
stringency: Gene amplification
& PCR glossary
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 glossary Related term: matrix
suspension arrays: Microarrays
categories
target (hybridization): Gene
amplification & PCR
G.O.T. Summit Getting
Optimized Targets April 10-13, 2007 • Boston, Massachusetts
theme arrays: Microarrays containing genes
thought to be involved in specific diseases or processes.
tissue arrays, tissue chips: Microarrays
categories tissue
microarrays
tox-chips: Pharmacogenomics glossary
transcript arrays: Microarrays
categories
ultra high density microarrays Microarrays
categories
Related term: bead based arrays
Broader term: density of
microarrays, high density oligonucleotide arrays
universal microarrays: Microarrays
categories
universal probe technologies: Gene
amplification & PCR glossary
variance: See under measurement error
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
Bibliography
BioChipNet Glossary, 2002, 150 + definitions http://www.biochipnet.com/glossary
Chipping Forecast III,
Nature Genetics, 37 (65): June 2005 http://www.nature.com/ng/journal/v37/n6s/index.html
Chipping Forecast II, Nature Genetics 32 (supp):
509- 514, 2002 http://www.nature.com/cgi-taf/dynapage.taf?file=/ng/journal/v32/n4s/index.html
“Chipping Forecast”, Nature Genetics supplement 21 (1s), Jan 1999 http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v21/n1s/index.html
MicroArray Explorer Glossary, NCI, Lab of Experimental & Computational
Biology http://www.lecb.ncifcrf.gov/searchframes.html
about 50 definitions.
Profiling Microarrays, Nature Genome Gateway - Post- Genomics http://www.nature.com/genomics/post-genomics/microarrays.html
DNA Microarray (Genome Chip), Leming Shi http://www.gene-chips.com/
Microarray related activities at the EBI, European Bioinformatics Institute,
UK http://www.ebi.ac.uk/microarray/
GRID IT Resources for Microarray Research, Virginia Tech/NC State Univ.,
US http://www.gridit.vt.edu/profile_VT.htm
MGuide, [Pat] Brown Lab’s Guide to Microarraying, Stanford Univ., US
http://cmgm.stanford.edu/pbrown/mguide/
MIAME Glossary, MGED,
2005 about 80 terms http://www.mged.org/Workgroups/MIAME/miame_glossary.html
Science Functional
Genomics Blog, Microarray Discussion, 2004 http://sciencemag.blogs.com/sfgblog/2004/10/a_microarray_di.html
Alpha
glossary index
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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