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Glossary Evolving terminology for emerging
technologies Comments? Suggestions? Revisions? Questions? mchitty@healthtech.com Last revised December 27, 2001 Industry leaders agree that multiplex array technologies are a key to realizing the therapeutic potential of genomic data; however, when microarrays will deliver on this potential and which companies will lead remain to be determined. The microarray industry is advancing rapidly but still faces technical and cost challenges.
Microarrays: Increasing the Capacity of Genomic
Analysis, CHI Report, April 2001. There is still a great deal of volatility in the area of microarray
terminology. See FAQ question # 2 for a methodology for investigating and quantitating use of various terms.
Note that
definitions for arrays - chips- microarrays vary widely in the
literature and are far from standard yet. Related glossaries are Applications Pharmacogenomics,
Informatics Algorithms & data management
Bioinformatics Technologies Assays
Labels, Signaling & Detection
Gene
Amplification & PCR; Miniaturization
Biology
Expression, Genetic
variations Additional Microarray definitions in the In-depth
glossary. AIMS Analysis Information Management System: Given the range and
complexity of data derived from microarrays, the demand for tools not just to
analyze those data but also to manage these types of projects will increase ...
AIMS, similar to the popular LIMS) is the ideal tool to meet the needs of this
array-intense phase of genomics research. The fundamental difference between a
LIMS and an AIMS is that the former tracks physical processes, while the later
tracks computational ones. AIMS are not yet commercially available, but they can
be created. [CHI Bioinformatics] Related term analysis - microarray data;
cluster analysis, image
analysis - microarrays, pattern recognition. analysis - microarray data: See data analysis - microarrays. array technology: See microarray. “Array technology”
in a broader context may refer to computer science, engineering and/ or
telecommunications. Array technologies include In-depth 2D gel electrophoresis,
CCDs Charged Coupled Devices, CCD cameras, detection technologies, fiber optics. imaging,
ink jetting, mass spectrometry,
photolithography, phosphorimagers, piezoelectric, semiconductors, spotting
robots. arrays: Narrower terms include bead based arrays,
bioarrays, bioelectronic arrays, cDNA arrays, cell arrays, DNA arrays, exon
arrays, filter arrays, gene arrays, gene expression arrays, genome arrays,
high density oligonucleotide arrays, hybridization arrays, macroarrays,
microelectronic arrays, multiplex DNA hybridization arrays, oligonucleotide
arrays, oligosaccharide arrays, protein arrays, small molecule microarrays,
spotted arrays, suspension arrays, tiling arrays, tissue arrays, transcript
arrays. Related terms include arrayed library. See also chips, microarrays. bead arrays: These arrays are made up of small beads containing
capture oligonucleotides encoded with fluorescent dye combinations or through
some equivalent means. Relative to conventional two-dimensional microarrays,
the bead arrays have larger surface- to- volume ratios, providing faster hybridization
kinetics, and they also offer much more flexibility and scalability in assay
design. [CHI SNP Update] Also known as encoded bead arrays. bead
based arrays: Arrays in which reactions take place on the surface of
microbeads. These arrays can contain hundreds of thousands to millions of
individual probes, making them perhaps the most promising technology for the
vast number of tests that will be needed for applications such as drug discovery
and for diagnosis and treatment of patients. [CHI Microarrays] Related
term fiber optics. biochip(s): An integrated circuit whose electrical and logical
functions are performed by protein molecules appropriately manipulated.
[IUPAC Biotech] bioelectronic arrays: See microelectronic arrays. 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. "Southerns, Northerns, Westerns, &
Cloning: "Molecular Searching" Techniques" MIT's Biology Hypertextbook
http://esg-www.mit.edu:8001/esgbio/rdna/rdna.html cDNA arrays: cDNA
clone inserts are robotically printed onto a glass slide and subsequently
hybridized to two differentially fluorescently labeled probes. The probes
are pools of cDNAs, which are generated after isolating mRNA from
cells or tissues in two states that one wishes to compare. [NHGRI, Microarray
Project] http://www.nhgri.nih.gov/DIR/LCG/15K/HTML/aboutmicro.html
See also the Schena definition under microarrays. Related terms arrayed
library, DNA chips, macroarrays cell arrays, cell microarrays: Cell assays performed
on a microarray. Related term tissue array. chemical microarrays: Molecular diversity immobilized on a chip surface is a highly efficient tool for the study of precious biological samples. Graffinity´s chemical microarrays present
molecular diversity of small organic molecules. A chemical shuttle process provides for the creation of
"arrayable" compounds: every compound synthesized at Graffinity is born with a reactive spacer moiety ("ChemTag") that releases the compounds after
solid- phase assembly and subsequently recaptures the molecules in the microarray format. This process generates soluble intermediates of chemtagged molecules for full quality control by
state- of- the- art LC/MS and mass production of microarray copies.
[Graffinity website, ChemTag R Array
Process", 2001] http://www.graffinity.com/techno/chemtag.html chips: A quartz or silicon substrate, generally either
part of a quartz or silicon wafer, less than 500 um in thickness. “Although the single chip approach is attractive, it is not critical that
all unit operations be performed on the chip. Important operations,
including sample preparation, preliminary reactions, piezoelectric sample
deposition and mass spectrometry frequently can, or must, be done with off- chip devices.
.. Integrating all these components … is perhaps the most
important issue. [F Regnier et al “Chromatography and electrophoresis
on chips” Trends in Biotechnology 17:101 March 1999] Narrower terms include GeneChipR , genome chip,
LabChipR, lab- on- a- chip,
oligonucleotide chips, protein chips In-depth biochips,
CellChipTM System, cell chips, microchips, microfluidics- based chips, SNP chips, tissue chips, glycochips,
lymphochip, pump
chips. See also arrays, microarrays. clones: Cell biology glossary Related term arrayed library. cluster analysis: Algorithms & data
management glossary Narrower term k- means clustering. DNA chips, DNA arrays, DNA microarrays: Also referred to as "microarrays."
Non- porous solid supports, such as glass have facilitated miniaturization
and fluorescence based detection. About 10,000 cDNAs can be robotically
spotted onto a microscope slide and hybridized with a double labeled probe,
using protocols pioneered by Pat Brown and colleagues [at Stanford University]
[Eric Lander "Array of hope" Nature Genetics 21 (1s): 3-4 Jan 1999] Related term
hybridization arrays data analysis - microarrays: Statistical analysis of gene expression
data is at an even earlier stage of development [than cluster analysis]. These
tests seek to establish some reliability or confidence measure for the changes
seen on arrays. While these tests generally do not determine whether the changes
are statistically significant, they are especially needed for ranking or
prioritizing genes whose expression levels need to be confirmed by post hoc testing
[CHI Microarrays] A new generation of "high- dimensional"
data- analysis (data- mining) tools are now entering the microarray marketplace. These types
of tools were developed to address data reduction in situations where the data
have multiple dimensions (as in predicting the movement of stock prices) and are
now being adapted for microarray work. [CHI Bioinformatics] Over 80 percent of laboratories using microarrays expect to increase their utilization over the
next year. However, with the "boom" of the technology also comes the need for careful navigation through interpretation of the data minefield. The facilitation of
adoption of standards for microarray experimental annotation, data representation, and the introduction of standard experimental controls and data
normalization
is critical Microarray
Data Analysis: Using Statistics and Standards to Navigate the Microarray Data Minefield
Nov. 12-14, 2001, Alexandria, VA Microarray
Data Analysis report, Nov. 2001 Focuses
on the data researchers get from these powerful instruments and the challenge of
designing experiments that yield statistically defensible results. Will describe
available commercial and academic software, as well as techniques that are still
in research. Topics include
normalization, filtering, clustering, and other pattern discovery methods,
biological interpretation of patterns, statistical issues pertaining to data
analysis and experimental design, custom chip design (including the use of
genomic sequence data to design custom oligo chips), and image analysis and will
discuss databases for storing microarray results and efforts to devise standards
for microarray data and databases. Related terms image analysis - microarrays; standards; cluster analysis,
pattern recognition Algorithms & data
management glossary data mining tools: See under data analysis - microarrays. dendrimer: Miniaturization
glossary density of microarrays: High- density arrays contain many tens of
thousands of genes per chip, whereas medium- and low- density contain on the
order of between a few thousand and a handful of genes per chip. [Todd R. Nelson
"Chip Chip Array: An analysis of DNA Chip Technology" Dain
Rauscher Wessels, Dec. 2000] http://www.tamirfishman.com/download/NELSON_DNA_Technology.pdf NCGR’s GeneX project was designed to
support as many technologies as possible including "high- density
silicon chip- based arrays (i.e., from Affymetrix and HySeq), medium- density
glass slide- spotted arrays, medium to low-density nylon
spotted arrays, Serial Analysis of Gene Expression (SAGE), Amplified Fragment
Length Polymorphisms (AFLP), Differential Display, and even Northerns
[blots]. http://www.ncgr.org/research/genex/whitepaper.html The entire yeast genome (6,000+ genes) has been put on a chip. Narrower terms
high density oligonucleotide arrays, macroarrays, ultra high density. See also Expression glossary. detection
technologies: Assays, labels, signaling & detection glossary GEML Gene Expression Markup Language: Expression
glossary gene arrays, gene microarrays: See DNA chip, DNA arrays, DNA
microarrays GeneChip ® is an Affymetrix product. Steve Fodor and colleagues
[at Affymetrix] have adapted photo- lithographic masking techniques
used in semiconductor manufacture to produce arrays with
400,000 distinct oligonucleotides. [Eric Lander "Array of hope" Nature
Genetics 21(1s):3-4, Jan 1999] gene expression arrays: Expression glossary genome arrays: The sequencing of complete genomes has made possible
whole genome arrays of bacteria and other organisms. Affymetrix has made E.
coli, yeast and Arabidopsis genome arrays. Used for
the study of gene expression and to determine co-regulated genes. Related terms
In-depth genome
chip, genomic arrays, genomic microarrays. high density oligonucleotide arrays: In this array format, probes are constructed directly on the surface of a slide
through photolithography. These chips provide the largest number of probes per
array of any array format. Affymetrix’s GeneChips of this type. [CHI
Microarrays] Broader terms oligonucleotide arrays, chips, microarrays,
microchips. hybridization arrays: DNA hybridization arrays are currently the most widely used tools for large-
scale analysis of gene expression and other genomic- level phenomena and
patterns. In all DNA array formats, gene- specific sequences (probes) are
immobilized on a solid- state matrix (nylon membranes, glass microscope
slides, silicon/ ceramic chips) and then queried with nucleic acids from
biological samples (targets). In gene expression studies, for instance, the
amount of target that hybridizes to the gene- specific probe gives a measure of
the abundance of that particular transcript within the sample. [CHI Microarrays]
Also called hybridization array assays image
analysis - microarrays: Involves gridding (in which a rectangular grid is
laid on top of the image), segmentation (used to determine where the spots lie
within the grid), and intensity extraction (a means of evaluating each spot).
The key informatics goal at this step is to record the results of the analysis.
Image- analysis software for gene expression studies is often bundled with the
imaging instruments and other products. [CHI Bioinformatics] 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] Analysis, Microarrays, Image Link Image analysis, Microarray Project (uAP), NHGRI, US http://www.nhgri.nih.gov/DIR/LCG/15K/HTML/img_analysis.html in situ array: Oligonucleotides are
constructed on the matrix. From the Latin "in situ" in place.
Related term Gene ChipR LabChipR is a Caliper product. lab-on-a-chip(s): Microfabricated fluidic system for performing
biochemical assays. [Gene Cards, Weizmann Institute, Israel] Related term microfluidics based chips.
http://bioinformatics.weizmann.ac.il/cards-bin/dicdisp?biochip Miniaturized platform technologies are no longer new concepts. Now is the time for proof of the principle for specific applications. Lab- on- a- Chip & Microarrays for Post Genomic Applications
Jan. 14-16 2002 Zurich, Switzerland Related terms biochip, LabChipR, protein
chip, In-depth microelectronic arrays, microfluidics based chips, pump chip,
tissue chip See also chips. low-density arrays: See under density of microarrays. Related term: macroarrays microarrays: Microarrays (in which nucleic acids
representing genes are spotted onto or synthesized on a substrate and then
tested against a sample) gauge mRNA levels - and thus gene expression. With
these tools, many different genes can be studied, enabling expression patterns
to be discerned in, for example, diseased versus normal tissue or in early-
stage
disease tissue versus late- stage disease tissue. [CHI Microarray] 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
] 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] This technology finds itself center stage thanks to the successful decoding
of the human genome. Regardless of its enormous potential, only recently has the
number of application papers surpassed that of review articles. In other words,
we have a technology that works well despite, rather than because of, our
understanding of the subject. Once again this Boston conference will highlight
the best advances in the hardware production and manufacturing of these
machines, but we will also examine critical questions to the application of
these tools, to their data analysis, and to the tacit assumptions researchers
have made in the larger biological picture- sometimes without enough skepticism
or innovation.
Microarrays Through Macroresults:
Advancing Drug Development
April 29- May 1, 2002 Boston, MA Narrower terms genomic microarrays, oligonucleotide arrays, protein microarrays,
In-depth antibody microarrays,
BAC microarrays, cell
microarrays, DNA microarrays, gene microarrays, gridded
cDNA microarrays, small molecule
microarrays, tissue microarrays. Related terms include data analysis -
microarrays, density of microarrays, probes - microarrays. See also arrays, chips. AMAD Another MicroArray Database, Joe DeRisi's Lab, Biochemistry &
Biophysics, Univ. of California- San Francisco, US http://www.microarrays.org/
Public source for software, technology and protocols. DNA Microarray (Genome Chip), Leming Shi http://www.gene-chips.com/ GRID IT Resources for Microarray Research, Virginia Tech/NC State Univ.,
US http://www.bsi.vt.edu/ralscher/gridit/ MGuide, [Pat] Brown Lab’s Guide to Microarraying, Stanford Univ., US
http://cmgm.stanford.edu/pbrown/mguide/ Microarray Project (uAP), NHGRI, US http://www.nhgri.nih.gov/DIR/LCG/15K/HTML/
Collaborative research effort among various NIH institutes and divisions. Microarray related activities at the EBI, European Bioinformatics Institute,
UK http://www.ebi.ac.uk/microarray/ 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 data analysis: See data analysis - microarrays. microarray- regulation: The FDA
is 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. [Joseph
Hackett, FDA, Center for Devices and Radiological Health How the Genomics
Revolution Affects FDA Regulation [http://www.chiresource.com/newsarticles/issue5-1.ASP
] microarray technologies: See array technologies. microchip: Miniaturization glossary microelectronic arrays (or microelectronic chips): These arrays, based on semiconductor
microfabrication techniques, are made up of microelectrodes capable of
generating a current that can be used to draw probes, samples, and reagents to
specific locations on the chip. This approach allows faster, more controlled
hybridization. [CHI Microarrays] See also under multiplex DNA
hybridization arrays micron: One one thousandth of a millimeter; 10,000 angstroms.
[NIGMS] Represented by u. microwell chips: Narrower term nanowells molecular bioprocessing: We
are combining the fields of biocatalysis, bioinformatics,
metabolic engineering, and high- throughput combinatorial biosynthesis with
microsystems engineering to form a new area of fundamental and applied research.
This new area, called "molecular bioprocessing" enables us to join the
technologies of combinatorial biosynthesis with high- throughput biocatalytic
technologies, which allows access to nature's "warehouse" of
structures and functions, and to be able to manipulate the synthesis of these
molecules to yield novel compounds and materials for use in the pharmaceutical,
chemical, and agrochemical industries. One aspect of molecular bioprocessing is
the in vitro fabrication and manipulation of single- and multi-enzyme systems on
a biochip; the logical extension being metabolic pathway engineering on the
microscale. [Jonathan S. Dordick, Rensselaer Polytechnic Institute,
"Metabolic engineering on a chip" CHI's Functional Genomics
conference, Oct. 9- 10 2001] http://www.functionalgenomics2001.com/fgen.htm multiplex DNA hybridization arrays: We will use the term DNA array
for any matrix containing multiple gene- specific sequences that permits
simultaneous evaluation of hundreds to thousands of individual genes. This term
will include nylon- membrane- based arrays (so- called macroarrays), microscope-
slide- based arrays (microarrays), silica chips with high- density
oligonucleotides constructed in situ (the Affymetrix GeneChip), and microelectronic arrays (a unique combination of addressable electrodes and gene-
specific fragments). All these formats fall under the description multiplex
DNA hybridization array. However, common usage in the field frequently
refers to all these formats as microarrays. [CHI Microarrays] nanoarray: nanochip: Miniaturization glossary nanowell: Aurora has developed a
manufacturing system for disposable NanoWell Assay Plates. A key feature is the
small assay volume, approximately 100 times smaller than most conventional
screening assays. This volume reduction is critical for reducing the cost per
test and conserving compound libraries that often consist of only very small
amounts of each test compound.... While current screening systems can dispense
volumes down to about one microliter (one millionth of a liter), Aurora has
developed miniaturized screening dispensers capable of dispensing volumes less
than one billionth of a liter. [Vertex Aurora Biosciences Corp, "Aurora
Platforms: UTHSS Ultra High Throughput Screening Systems, 2001] http://www.aurorabio.com/discovery/automation/uhtss.html normalization: Algorithms & data
management glossary 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] Useful to know this MeSH heading for microarrays, but use free- text as
well to search PubMed. oligonucleotide arrays, chips, microarrays, microchips: 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 … or expression or for gene mapping. [MeSH ‘oligonucleotide array
sequence analysis’] pattern recognition: Algorithms &
data management glossary 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]
Has this changed? Can be made from clones, PCR
amplicons or oligonucleotides. See also probes Gene
amplification & PCR protein arrays: Microarrays have revolutionized genomic studies. Protein arrays have the same potential to impact
proteomics. Protein arrays can be used to screen for interaction of proteins with other
proteins, DNA, antibodies, cells, or small molecules. The two major formats designed to serve rather different applications present different technical challenges and opportunities. Immobilization of numerous proteins requires efficient
protein expression and strategies that retain activity. Determination and quantification of protein expression levels require arrays designed to selectively capture proteins in solution. Numerous technical obstacles, such as optimizing protein immobilization or selection of
protein- binding ligands, strategies for extending the limits of detection, and novel applications of this exciting technology, are among the issues that will be discussed in detail. Protein Arrays: Technology and Applications January 7-8,
2002 San Diego CA Protein
and peptide arrays:
Proteins to profits Mar. 25-27, 2001 Munich, Germany 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] The goal of developers of protein arrays is to allow thousands of
proteins to be studied en masse, the way gene expression
is currently studied. These arrays could be used to study protein
expression, protein- protein interactions, and the interactions between
arrayed proteins and potential drugs. Specifically, arrays of a series of
protein targets could be used to identify binding of particular proteins or small
molecules (e.g., potential therapeutics) to these targets. Or multiple
compounds could be screened for activity, in a parallel fashion, against a
single protein target deposited at multiple locations on an array. In drug-
screening applications, protein arrays could help researchers determine
which compounds react with target proteins and which react with non- target
proteins, potentially causing side effects. [CHI Target Validation] Related terms protein chips, protein microarrays.
Narrower term proteome chip. protein chips: With more than a dozen companies poised to enter the market, sales of protein chips are likely to balloon from $45 million in 2000 to almost $500 million in
2006 ... In a new report, BioInsights has identified and analyzed 20 companies that are likely to join current protein chip makers Biacore and Ciphergen in their attempt to meet the strong demand for
high- throughput analysis of proteins.
[BioInsights, Protein Chips: The Race for High-Throughput Protein
Analysis, Dec. 2000] http://www.chireports.com/pressrelease/prochips.asp 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. [CHI Summit Proteomics] 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, but are at an earlier stage
of development. Related terms protein arrays, protein microarrays; Narrower
term proteome chip protein microarrays. Protein
microarrays will permit researchers to scan thousands of proteins in a variety
of proteomic experiments, including differential expression, response to drugs, protein- protein interactions and identification of disease biomarkers. So far,
they have proven to be very quantitative and, by virtue of their addressable
arrays, much easier to compare results between experiments than 2D gels.
Commercialization of protein arrays also promises rapid development toward real
applications in clinical and point- of- care diagnostics, which would be
impossible with more complex proteomic technologies that require electrophoresis
or chromatography. One disadvantage of the microarray approach is that generally
it is a "closed" system - you can only measure proteins for which you
have a capturing agent (such as an antibody). [CHI Summit Proteomics] In conjunction with high throughput expression
and purification of recombinant proteins, we can prepare microarrays of
functionally active proteins on glass slides. These arrays can then be
used to identify protein- protein interactions, to identify the substrates
of protein kinases, or to identify the targets of biologically active small
molecules. [Harvard Center for Genomic Research, MacBeath Lab, Overview] http://www.cgr.harvard.edu/macbeath/index.html Haab BB, Dunham MJ, Brown PO. Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions. Genome Biol. 2001 Jan 22; 2(2): RESEARCH 0004.1-0004.13. Related
terms protein arrays, protein chips; Narrower term proteome chip. proteome
chip: Michael Snyder (Yale Univ.) and colleagues cloned 5800 ORFs from yeast
and printed the overexpressed purified proteins onto microarrays to investigate
protein- protein interactions. A number of potential applications for proteome
chips can be envisioned. [Zhu H. et. al, "Global analysis of protein
activities using proteome chips" Science July 26, 2001 epub ] Broader terms
protein arrays, protein chips, protein microarrays. RNA
biochip: Advanced versions of our prototype RNA biochip can be used to see many different
targets like drugs, toxins and metabolites, as well as both proteins and nucleic acids," he
[Ronald Breaker] says. "We even have a molecular switch that can be triggered indirectly by UV light. In other words, our RNAs fold into intricate 3-D structures that selectively recognize a wide range of targets, a function that is similar to antibodies. Therefore, advanced RNA biochips should be able to be used to detect almost anything that an RNA can be made to bind."
http://www.yale.edu/opa/v29.n26/story15.html
[Yale scientists create RNA biochip" Yale Bulletin and Calendar 29 (26)
April 13, 2001] Related term Pharmaceutical
biology glossary allosteric ribozymes 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 call this
approach 'reverse transfection' and 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 scanning technologies: See
In-depth fluorescent scanners, laser scanning phosphorimagers Related term image analysis - microarrays
See also Imaging
glossary, Mass Spectrometry semiconductor:
Miniaturization glossary spotted arrays: See cDNA arrays. standards: See GEML In-depth glossary ArrayExpress, MAML, MGED,
MIAMI; Expression glossary 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 In-depth microspotting, spotted arrays,
spotting robots. target (hybridization): Gene
amplification & PCR ultra dense oligonucleotide arrays: ultra high density microarrays Contain hundred to thousands to millions of
features. Able to run many types of assays, not just DNA hybridization. [CHI
Microarrays] Related term bead based arrays. Broader term density of
microarrays, high density oligonucleotide arrays Bibliography Nature Genetics, “Chipping Forecast” supplement 21 (1s), Jan 1999 http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v21/n1s/index.html [CHI Microarrays]: Increasing the Capacity of Genomic Analysis, April
2001. http://www.chireports.com/content/reports/chips.asp Alpha
glossary index 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. In-depth microarrays glossary 2D electrophoresis: Chromatography
& electrophoresis glossary antibody microarrays. While transcriptional profiling provides
invaluable insight into biological function on a genome- wide scale, it
doesn't offer information on regulation that occurs at the protein level
(e.g., degradation, phosphorylation/ dephosphorylation, sub- cellular localization,
etc.). We are investigating the possibility of using microarrays of antibodies
to study regulation at the protein level. Harvard Center for Genomic Research,
MacBeath Lab] http://www.cgr.harvard.edu/macbeath/index.html ArrayExpress: The EBI has discussed the possibility of establishing a public repository for DNA microarray based gene expression data with many of the major laboratories developing and using these technologies in Europe and the USA. Following these discussions, the European Bioinformatics Institute is committed to establishing a public repository for microarray based gene expression data, named ArrayExpress. Currently the EBI is establishing a pilot database containing microarray gene expression data that are available publicly.
[European Bioinformatics Institute, ArrayExpress, 2001] http://www.ebi.ac.uk/arrayexpress/index.html
Related terms data analysis - microarrays; standards. 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 library, genomic
library. (Cell biology glossary) BAC microarrays: Mapped DNA fragments are arrayed onto a glass surface
and covalently coupled using proprietary chemical processes Have
potential for using for high- resolution, high- throughput, genomic
profiling. [Dr. Shirshir Shah CHI's Application of Genomics to Animal
Models, Oct. 11-12, 2001 Cambridge MA http://www.functionalgenomics2001.com/amodels.htm bioarrays: Gene expression arrays, also known as bioarrays.
["Motorola first to license Incyte's gene patent portfolio... for bioarray
commercialization" Incyte press release Aug. 17, 2000] http://www.incyte.com/company/news/2000/08_bioarray_commercialization.shtml CCD Charged Coupled Device: Imaging
glossary cell chips: The in vitro analysis of cell genomic activity has been revolutionized by a variety of chip
technologies. Further important advances can be expected as high resolution analytical
approaches are utilized to interrogate chips. [National Center for Research
Resources "Integrated Genomics Technologies Workshop Report" Jan
1999] http://www.ncrr.nih.gov/newspub/genomic.pdf CellChip™ System: A miniaturized automated platform that performs
both High Throughput Screening and High Content Screening on microarrays of
selectively localized living cells on chips. [Cellomics, Inc. website] http://www.cellomics.com exon arrays: Used to confirm predicted exons, described in
D.D. Shoemaker et.
al "Experimental
annotation of the human genome using microarray technology" Nature
409, 922-927, 15 Feb. 2001. Related term tiling arrays. fiber optics:
Imaging glossary filter arrays: Filters on which clones or purified cDNAs
have been arrayed at high density to provide targets for reverse- transcribed
probes. [D Bowtell “Options available – from start to finish — for obtaining
expression data by microarray” Nature Genetics 20 (1s): 25-32 Jan 1999] 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 Microarray] See also Imaging
glossary genome chip: Technology is meant to monitor the whole genome
on a single chip. GenomeChip would also include the increasingly important
and feasible protein chip technology. [Leming Shi “DNA Microarrays”
1998-2000] http://www.gene-chips.com/
Related terms genome arrays, genomic arrays, genomic microarrays. genomic arrays: Allow toxicologists to look at cellular behavior in a completely new light. In a sense, recording individual gene responses to
powerful insults such as alkylating agents was akin to studying the effects of poverty by monitoring a person's bank
account - the complete picture is much larger than what is actually being measured. But genomic arrays simultaneously report indicators of multiple dimensions of the
cellular response to stimuli. Now, in addition to gaining insight into basic cellular mechanisms of repair, researchers looking at a variety of
indicators and responses of toxicity may gain some predictive power regarding individual
compounds - and individual humans. Both academic and private laboratories have already begun work on finding genes that induce protection or sensitivity to toxicants in
individual cells and people. [NIEHS News "Arrays cast toxicology in a new
light" Environmental Health Perspectives 09 (1), Jan. 2001]
http://ehpnet1.niehs.nih.gov/docs/2001/109-1/niehsnews.html
Related terms genome arrays, genome chip, genomic microarrays. genomic microarrays: Genomic microarray technology allows assessment
of multiple gene targets for identification of gene amplifications
or deletions in a variety of different sample types. [Vysis
Products] http://www.vysis.com/products_sect.asp?ProductLineID=14
Related terms genome arrays, genome chip, genomic arrays. Narrower term GenosensorTM system Genosensor ™ System: Utilizing Vysis’ patented comparative genomic
hybridization (CGH) technology to simultaneously survey multiple gene targets,
the GenoSensor System is able to screen multiple gene targets in a single
test. [Vysis Products “GenoSensor System] http://www.vysis.com/products_sect.asp?ProductLineID=14 glycochips, oligosaccharide arrays: Still at a fairly preliminary
research stage for now. gridded cDNA microarrays: See cDNA arrays. 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] laser: Imaging glossary Related
terms CCD, image analysis, scanning technology. laser scanning: Imaging glossary lymphochip: A specialized DNA microarray, termed the "Lymphochip",
that is enriched in genes which are selectively expressed in lymphocytes and
genes which regulate lymphocyte function (1).
Since the majority of human lymphomas appear to represent malignant
transformation of the germinal center B lymphocyte, a cDNA library was created
from germinal center B lymphocytes that were purified by flow sorting from human
tonsils. [Louis Staudt Lab "Current Projects" NCI, NIH 2001] http://lymphochip.nih.gov/current.html MAML Microarray Markup Language: A data format for describing information about
DNA- array based experiments. MAML is based on the Extensible Markup Language (XML). MAML provides a framework for describing experiments done on all types of DNA-arrays, including spotted and synthesized arrays, and
oligo- nucleotide and cDNA arrays. It is independent of the particular image analysis and data normalization methods, and allows representation of both raw and processed microarray data. Over and above the representation of expression measurements, it allows for comprehensive annotation of experimental results. The format is
compatible with the definition of the minimum information about a microarray experiment
(MIAME), but does not impose its requirements.
[MAML specification primer Draft Jan. 19, 2001] Broader term standards
Related terms data analysis - microarray, MGED, MIAME http://www.ncbi.nlm.nih.gov/geo/maml/ MGED
Microarray Gene Expression Database group: An open discussion group initially established at the Microarray Gene Expression Database meeting MGED 1 (November, 1999, Cambridge, UK). The goal of the group 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 normalisation methods. The underlying goal is to facilitate the establishing of gene expression data repositories, comparability of gene expression data from different sources and interoperability of different gene expression databases and data analysis software.
http://www.mged.org/ Broader term standards
Related terms data analysis - microarray, MAML, MIAME. MIAME
Minimum Information About a Microarray Experiment: The goal of the MIAME is to specify the minimum information that must be reported about a microarray (or any DNA array) based gene expression monitoring experiment in order to ensure the interpretability, as well as potential verification of the results by third parties. The background aim is to facilitate the establishing public repositories and data exchange format for microarray based gene expression data. The MGED group will be encouraging the scientific journals and funding agencies to adopt policies requiring data submissions to repositories, once MIAME compliant repositories are established.
The definition of the minimum information is aimed at co- operative data providers, and not
for closing possible loopholes in not providing the information.
[Annotations Working Group, MGED] http://www.mged.org/Annotations-wg/index.html
Broader term standards, Related terms data analysis - microarray, MAML, MGED. macroarrays:
Arrays on which gene-specific probes are robotically spotted onto a
nitrocellulose or nylon membrane substrate. The term macroarray refers to
the typically lower probe density for these arrays as opposed to microarrays.
Generally, macroarrays are the simplest array format and use radioisotopic
methods for detection. Note that definitions for arrays vary widely in the
literature. [CHI Microarrays] Narrower term nylon macroarrays. 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] 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. microchips: Implantable chips for gene delivery [CHI Microarrays] microfluidic devices: Miniaturization
glossary microfluidics-based chips: These chips, which contain tiny channels in
which the movement of fluids is controlled, allow the integration and
miniaturization of a range of laboratory processes. Because of their small
scale, these devices require much lower quantities of chemicals and test
materials than those used in traditional molecular- biological approaches. [CHI
Microarray] microspheres: Microspheres are generally defined as
small spheres made of any material and sized from about 0.5 µm to 100 µm.
Similar, but smaller spheres sized 10 to 500 nm are called nanospheres. Ideally,
microspheres are completely spherical and homogeneous in size,
although less perfect particles are often termed microspheres as well.
Depending on the preparation method and material used, microspheres show a
typical size distribution which often deviates from the mono- sized ideal. [Urs Häfeli
"Radioactive Microspheres for Medical Applications" High Care Bochum
Germany Feb. 25-27, 2000]
http://www.highcare.de/abstracts/HTML0051.htm 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;
In-depth spotted arrays, spotting robots. Northern blotting: Detection of RNA that has been electrophoretically
separated and immobilized by blotting on nitrocellulose or other type of
paper or nylon membrane. [MeSH] nylon macroarrays: High density membranes, in which cDNA
colonies or polymerase chain reaction (PCR) products are regularly arranged
with a spot spacing (“pitch”) of 1 to 2 mm have been used for some time
with expression measurements with radioactive complex probes. [Note] There
is a certain tendency by some firms to call their macroarrays “microarrays”.
[S Granjeaud “Expression profiling: DNA arrays in many guises” BioEssays
21: 781-790 Sept 1999] Broader term macroarrays peptide arrays: Steve Fodor and colleagues at Affymax published
several articles on these in the early 1990s. Related terms protein arrays,
protein chips, protein microarrays phenotype microarray: Designed
to study a range of cell properties (phenotypes) as a means of understanding how
a gene or a drug affects living cells - a critical step in identifying potential
new drug targets and in developing safe and effective new drugs. Biolog's
proprietary PM [phenotype microarray] technology provides researchers with
powerful, efficient and cost- effective information for determining gene
function by directly measuring the consequence of a genetic change on cellular
phenotypes. This technology allows researchers to test hundreds to thousands of
cell properties simultaneously, and also has applications in validating and
optimizing drug targets, determining a drug's mode of action, assessing
toxicology, and basic cellular research. The patented method involves the use of
PMs to conduct a very detailed comparison of two cell lines, one of which has
been modified by a gene mutation or tested with a drug lead. [Biolog, Inc.
"Biolog expands Phenotype Microarray AssayTM
for Cell- Based Analysis, Jan. 9, 2001] http://www.biolog.com/010901-BiologExpandsPhenotypeMicroArrayAssay.htm
Broader term Genomics glossary phenotype phosphorimagers: Instruments used to quantify the radioactive signal
(an indication of the level of hybridization) produced by macroarrays. [CHI
Microarrays] 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. [CHI Microarrays] Related term soft lithography piezoelectric: Some crystals, especially quartz, will produce an electric charge when squeezed. This charge will typically be high voltage and low amperage.
[International Tesla Society Scientific Dictionary, 1996] http://www.studytech.com/cgi-bin/cgiwrap/bware/dotesla.cgi?word=piezoelectric pump chip: The German company GeSiM uses technology based on ink- jet
printing in its piezoelectric pump devices for spotting microarrays. The
dispensing head of this device can be considered a "pump chip" (micropipettor),
which consists of a glass (or other) support, constructed with an orifice and an
inlet hole for the fluid to be dispensed. Just in front of the orifice is a pump
chamber with a piezoactuator on one side. The piezoactuator transforms an
electric current into a mechanical force that drives a small drip from a fluid
chamber out the orifice. The amount of electric current used controls the size
of the drop. [CHI Microarrays] SNP chips: Microarrays used for genome wide genotyping of single
nucleotide polymorphisms (SNPs). Related term Genetic variations
glossary SNP semi-conductor: Miniaturization
& nanoscience glossary small molecule microarrays: By fabricating microarrays of small
molecules (prepared by split- and- pool synthesis), we can screen large libraries
of compounds very efficiently to identify new ligands for (almost) any
protein of interest. Such ligands can then be used to study the biological
role of its protein target by perturbing its function in vivo. [Harvard
Center for Genomic Research, MacBeath Lab, Overview] http://www.cgr.harvard.edu/macbeath/index.html 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 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] The Southern blot was the first array. [Eric Lander "Array of hope" Nature Genetics 21 (1s): 3-4 Jan 1999] 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. [CHI Microarrays] Related terms Stokes shift; In-depth
microspotting, spotted arrays. 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. [CHI
Microarrays] Different from substrate Pharmaceutical
biology glossary Related term matrix suspension arrays: Luminex has demonstrated a DNA- based tissue typing assay that determines the haplotype of the DQA1 locus in less than 30 minutes following sample amplification. This
multi- analyte DNA hybridization system analyzed 16 unique sequences with single base discrimination. Oligonucleotide probes complementary to the alleles of interest were coupled to fluorescently coded
microspheres.
Fluorescein- labeled probes complementary to the microsphere bound oligonucleotide sequences were used to interrogate each microsphere. The microspheres and fluorescent probes were hybridized in the presence of an amplified DNA sample and analyzed. The presence of a specific sequence in the sample was determined by
competitive
hybridization. This assay demonstrated the utility of the Luminex R/O system and its Suspension Arrays™ for simultaneous interrogation of multiple nucleic acid sequences.
[Luminex Technical Bulletins "DNA based tissue typing" 1998] http://www.luminexcorp.com/tech/bulletins/DNA98.htm tiling arrays: Used to refine the precise exon structures of genes in a genomic region of
interest, described in D.D. Shoemaker et.
al "Experimental
annotation of the human genome using microarray technology" Nature
409, 922-927, 15 Feb. 2001. Related term exon arrays. tissue arrays, tissue chips, tissue microarrays:
A microarray
that permits massive parallel processing of biological samples. But unlike
the DNA chip, the tissue chip makes it possible for researchers to simultaneously
compare a variety of molecular markers… in cancer tissues from hundreds
[to a thousand patients. in a single tumor tissue microarray]. [Media
release on J Kononen et al “Tissue microarrays for high-throughput molecular
profiling of tumor specimens” Nature Medicine 4(7): 844-847 July 1998]
http://www.nhgri.nih.gov/NEWS/Gene_Therapy.html
Related term lymphochip transcript arrays: Uses patterns to interrogate gene function. [CHI
Microarrays] 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]. |