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homepage/Search > Biology > Expression genes & more Expression,
genes & more glossary Evolving terminology for emerging
technologiesSuggestions? Comments? Questions? mchitty@healthtech.com Last revised December 26, 2001 .
In an era when vast amounts of information
on all human genetic material are becoming available, the "one- gene- at-
a- time"
approach to monitoring gene expression is wholly inadequate. Not
only would such an approach be inefficient, it would not sufficiently illuminate
patterns of gene expression. The gene expression analysis field is going
through a period of dramatic innovation, and tremendous opportunities lie
ahead for companies in this field. Kent Vrana and Williard Freeman,
Genomic-
Scale
Gene Expression Analysis: Advancing from DNA to Disease, CHI Report 6,
Nov. 2000. Related glossaries are Applications Functional
Genomics, Genomics,
Proteomics,
Sequencing, Informatics Algorithms
& data management Bioinformatics,
Technologies Microarrays, Biology Sequences,
DNA & beyond. analysis - gene expression analysis: Large- scale
methods for analyzing gene expression patterns are needed. The current
challenge is to develop and optimize methods for monitoring these and the
gene products simultaneously. What is needed is genomic scale analysis
of gene expression. [CHI Gene Expression] Related terms post hoc testing,
statistical analysis; cluster analysis, pattern recognition, In-depth
guilt by association Algorithms
glossary data analysis, standards Microarrays
glossary analysis - protein expression: Remarkable advances are taking place in
protein expression analysis, but major hurdles still loom ahead. 2D gels must be
completely eliminated because they are so cumbersome, and all the steps in
protein expression study must become much more easily reproducible and more
affordable before they will enable researchers to significantly further our
knowledge of protein expression. Another major challenge is to improve
quantification of proteins. It is not sufficient to find a protein is expressed;
one must also know how much is expressed to be able to identify important
patterns. [CHI Bioinformatics] alternative transcripts: When a gene is expressed in different tissues, the cells frequently create variations in mRNAs. Processes such as alternative initiation,
splicing and polyadenylation generates transcripts that may be unique to (or enriched in) specific tissues. These alternative transcripts
sometimes encode an alternative form of the protein or may encode an identical protein, depending upon whether or not the sequence variation
affects the reading frame. This diversity provides the opportunity to make drugs that bind to the region of RNA unique to the desired tissue
and not affect the RNA in other tissues.
This opportunity for an additional level of drug specificity generally is not available targeting proteins. An analogous opportunity for
specificity at the protein level might be post- translational modifications of proteins that are tissue specific. In practice, however, this is variation
in proteins has been difficult to exploit or even understand due to the lack of good analytical tools to sort out
tissue- specific protein modifications. In contrast, finding alternative transcript forms in RNA is accomplished by straightforward sequencing of cDNA libraries
obtained from different tissues. The potential to find alternative transcript forms is one of the unappreciated strategic advantages of RNA as a
drug target. [Ibis Therapeutics "Small molecule drugs that bind RNA"
2000] http://www.ibisrna.com/darpa_ii/overview.html cluster analysis: Algorithms & data
management glossary clinical profiling of gene expression:
Gene
expression profiling has the potential to be used for differentiating types
of cancer (and other diseases) that appear identical to pathologists today.
Once the technologies are capable of high throughput and sufficient specificity and reproducibility this
will represent large potential markets for diagnostics, choosing
appropriate therapies and ongoing monitoring. conditional gene expression: When
gene expression is activated or suppressed at will. [CHI Functional Genomics] co-regulation: Correlated change(s)
in gene or protein expression diauxic shift: A shift in gene expression
that occurs when cells are transferred from a rich medium to a poorer medium,
or when cells in a rich medium grow and deplete their medium of nutrients.
[CHI Functional Genomics]. differential display: Use of quantitative
reverse transcription- polymerase chain reaction (QRT-PCR) to amplify
differences in gene expression between different cells or tissues. Specifically,
individual dinucleotides, coupled to oligo- dT primers (polymers of 12-18
deoxythymnidine residues), are used to initiate first- strand cDNA synthesis
with reverse transcriptase. These single- strand cDNAs are then amplified
using PCR
in such a manner as to randomly visualize the mRNA products. Researchers
then resolve the radioactive products from two experimental samples on
long denaturing polyacrylamide sequencing gels and look for quantitative
differences (intensities) in the signals These differences are assumed
to reflect variations in the starting amounts of RNA. [CHI Gene Expression] Related term RT-PCR Gene
amplification & PCR glossary Differential Gene Expression DGE: DGE and proteomics are screening technologies that are widely used for target validation.
They detect different levels and/or patterns of gene and protein expression
in tissues, which may be used to imply a relationship to a disease affecting
that tissue … the proof- of- concept experiments to demonstrate that differences
in the tissue expression of a particular gene are related to disease expression
(two very different meanings to ‘expression’) have not been performed in
any common disease with known susceptibility genes. [Allen D. Roses” Pharmacogenetics
and the practice of medicine” Nature 405: 857-865 June 15, 2000] An important tool for assembling exons into genes. [D. Shoemaker et. al.
"Experimental annotation of the human genome using microarray
technology" Nature 6822: 925, 15 Feb. 2001] Related terms In-depth EVGs; exon arrays Microarrays
glossary In
disease … the up- or downregulation of gene activity can either be the cause
of the pathophysiology or the result of the disease. ..The opportunity
to compare the expression of thousands of genes between ‘disease’ and ‘normal’
tissues and cells will allow the identification of multiple potential targets.
[C Debouck “DNA microarrays in drug discovery and development” Nature Genetics
21 (1s): 48-50 Jan 1999] Differential Protein Expression DPE: Great anticipation surrounds the
area of protein expression analysis. Currently, these studies use difficult- to-
standardize two- dimensional (2D) gels and expensive mass spectrometry. As a
result, this field is highly specialized and mainly involves academics or others
working on very focused projects, as well as a handful of large- scale efforts.
[CHI Target Validation] downregulation: Process that decreases ligand/ receptor interactions
due
to a reduction in the number of available receptors … Classically the concept
referred to hormone receptors but contemporary usage includes other cell
surface receptors. [MeSH/Metathesaurus] EVGs Expression Verified Genes: Co- regulated exons, from Chromosome 22 (the first human chromosome to be
completely sequenced) and used as a benchmark for computational and experimental
analytical methods. Expression data can define gene boundaries because adjacent
exons that are co- regulated across many conditions are likely to be from the
same transcript. Hybridization data defining EVGs could be useful to
"train" next generation gene prediction algorithms. [D. Shoemaker et.
al. "Experimental annotation of the human genome using microarray
technology" Nature 6822: 922-927, 15 Feb. 2001] expression: The cellular production
of the protein encoded by a particular gene. The process includes
transcription of DNA, processing of the resulting mRNA product and its
translation into an active protein. N.B. A recombinant gene inserted
into a host cell by means of a vector is said to be expressed if the synthesis
of the encoded polypeptide can be demonstrated. [IUPAC Bioinorganic,
IUPAC Compendium] A description as to how a gene demonstrates
a phenotype. This can range from production of a mRNA to a disease.
If a disease gene carrier shows signs of the disease gene, then that gene
is expressed. Note that an individual must carry the disease gene
and be penetrant for it before the term expression is utilized. [NHLBI] Narrower terms gene expression, protein expression, mRNA
expression, RNA expression, transcript expression. Expression Software
See Databases & software
directory expression mapping, Maps genomic & genetic expression maps Maps genomic & genetic
Narrower terms: protein expression map, self- organizing maps, transcript maps
Related terms:EST maps, genome control maps expression pharmacogenomics: Pharmacogenomics
glossary expression product: Related term gene product Gene
definitions expression profiling, expression profiles: Narrower terms gene
expression profiling, protein expression profiling, transcript
profiling. Related terms gene expression, protein expression, RNA
expression, transcript expression. expression profiling sensitivity: Discussions about the limits
of sensitivity of these methods is often confused … Performance is generally
stated as the minimal (relative) abundance of mRNA that can be detected,
i.e. 1/300,000 or “one copy per cell” (assuming a mammalian cell
contains 300,000 individual mRNA molecules). This abundance must be related,
however, to the probe concentration, and ultimately, to the size of the
starting biological sample that is the experimentally relevant (and often
limiting parameter … We feel that a realistic evaluation of sensitivity can
be expressed ass the minimum number of molecules of one particular sequence
species in the sample needed to obtain a measurable signal on the corresponding
target after hybridisation. [S Granjeaud “Expression profiling: DNA arrays
in many guises” BioEssays 21: 781-790, Sept. 1999] expression proteomics: Large- scale
measurements of protein expression. [CHI Proteomics] The ability to measure protein- level changes
directly would seem to carry inherent advantages and it seems likely that
expression proteomics will be a useful tool in drug target discovery and
in studying the effects of various biological stimuli on the cell. [Weir
& Blackstock “Proteomics” Trends in Biotechnology: 121-134 Mar
1999] expression technologies: Chromatography
& electrophoresis, Gene
amplification & PCR Microarrays have been a breakthrough
technology for studying gene expression. Narrower terms differential display, SAGE, subtraction cloning, TOGA. GEML Gene Expression Markup Language:
An Extensible Markup Language (XML) based tag set, was developed by Rosetta
Inpharmatics and others in the GEML community to provide a standard method
of exchanging gene expression data along with the associated gene and experiment
annotation. http://www.geml.org
Related terms analysis- gene expression; data analysis, standards Microarrays
glossary gene clustering: Related terms Algorithms
glossary cluster analysis, hierarchical clustering, self organizing maps; Microarrays
glossary k- means clustering; gene expression: The process by
which a gene’s coded information is converted into the structures present
and operating in the cell. Expressed genes include those that are
transcribed into mRNA and then translated into protein and those that are
transcribed into RNA but not translated into protein (e.g. transfer [tRNA] and ribosomal [rRNA] RNAs). [DOE] The transcription and processing of an
mRNA or the transcription and translation of RNA in order to produce a
functional protein. [CHI Gene Expression] Our modern concept of gene expression dates
back to 1961 when messenger RNA was discovered, the genetic code was deciphered,
and the theory of genetic regulation of protein synthesis was described. [O
Ermolaeva et al “Data Management and analysis for gene expression arrays”
Nature Genetics 20:19-23,1998]http://www.nhgri.nih.gov/DIR/LCG/15K/HTML/ng_paper.html Broader terms expression,
genome expression. Gene expression databases see Databases
& software directory. gene expression arrays: Used in drug development to screen drug candidates against cell lines and compare
the effects of drug candidates with those of existing "gold standard" drugs
on gene expression. Also used to monitor patients on clinical trials. [CHI
Gene Expression] gene expression monitoring: Significant challenges are to be met in understanding the pathways that exist in gene regulation and the expression and utility of proteins. More robust computational methods are required to analyze gene expression data for higher accuracy and predictive value. Integrative
Bioinformatics High- throughput interpretation of pathways and biology Jan.
16 - 18, 2002
Zurich, Switzerland gene expression profiling: Involves
studying the expression (as mRNA) of thousands of genes in a cell or tissue, and
how gene expression changes under various conditions. ... A major goal of
expression- profiling studies is to gain evidence for coordinate control of the
expression of sets of genes. In studying a disease process, one is interested in
how the expression of large sets of genes may covary in health and disease. Such
analysis is expected to help elucidate gene regulatory networks (e.g.,
molecular networks within the cell by which groups of genes are coordinately
controlled) and biochemical pathways. It is also expected to help
researchers determine how intracellular networks and pathways may be disrupted
in disease processes or altered by drugs. [CHI Target Validation]
The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell.
[MeSH] Related terms expression
profile, expression profiling. Related term protein expression, gene
shaving: A statistical method, which we have called 'gene shaving'. The method
identifies subsets of genes with coherent expression patterns and large
variation across conditions. Gene shaving differs from hierarchical clustering
and other widely used methods for analyzing gene expression studies in that
genes may belong to more than one cluster, and the clustering may be supervised
by an outcome measure. The technique can be 'unsupervised', that is, the genes
and samples are treated as unlabeled, or partially or fully supervised by using
known properties of the genes or samples to assist in finding meaningful
groupings. [Trevor Hastie et. al. "'Gene shaving' as a method for
identifying distinct sets of genes with similar expression patterns" Genome
Biology 1(2): 003, 2000] gene transcription: See transcription. genetic profile, genetic profiling: The
description of an individual which lists the significant genetic characteristics
of an individual to establish identify, relationship, genetic predisposition
to certain traits or diseases and other genetic specifics. [OED] Also known as genetic fingerprinting
[Oxford Biochem] genome expression,: Gene expression
at the whole- genome level. Related term global gene expression. Or are these equivalent? genomic profile, genomic profiling:
The recent development of genome- wide expression profiling (chip, microarray or Serial
Analysis of Gene Expression [SAGE] technologies) allows a comprehensive
high- throughput screening of the effects of an insult (genetic, physiologic,
pathologic, etc.) on gene expression in tissues and specific cell populations
of interest. These techniques may aid in determining the function
of a newly discovered gene or discovering new biomarkers and therapeutics
for patients with disease. [NIDDK Biotechnology Centers, Release Date:
September 23, 1999, RFA: DK-00-002, National Institute of Diabetes and
Digestive and Kidney Diseases, US] http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-00-002.html global gene expression: From experiments on global gene expression, we
may obtain data for thousands of genes, often forcing us to consider processes,
function and mechanisms about which we know very little. Thus, there is
a need for more sophisticated systems of knowledge representation (or ‘knowledge
bases’) that organize the data, facts, observations, relationships and
even hypotheses that form the basis of our current scientific understanding … Unfortunately
the fact that the scientific literature has been somewhat haphazardly built,
without the benefit of a controlled or restricted vocabulary and a well
defined semantic and grammar. To take full advantage of the abilities
of the new technologies and the rapidly increasing amount of sequence information
it is absolutely essential to incorporate the facts, ideas, connections,
observations and so forth, which exist in the scientific literature and
in the minds of scientists, into a form that is systematic, organized,
linked, visualized and searchable. An often overlooked aspect of measurements
of global gene expression is that the sequence or even the origin of the
arrayed probes does not need to be known to make interesting observations ... The basic idea is
that if a drug interacts with and inactivates a specific cellular protein,
the phenotype of the drug- treated cell should be very similar to the phenotype
of a cell in which the gene encoding the protein has been genetically inactivated,
usually through mutation. [David J. Lockhart & Elizabeth A Winzeler
“Genomics, gene expression and DNA arrays” Nature 405: 827-836 June 15,
2000] The first attempts at global surveys of gene expression were undertaken
in the mid- 1970s … The serial methods involve direct, large scale sequencing
of cDNAs … the parallel approaches are based upon hybridization to
cDNAs immobilized on glass (microarrays) or to synthetic oligonucleotides
immobilized on silica wafers or "chips". . We note that bioinformatics
needs are similar and equally essential for all methods. [O
Ermolaeva et al “Data Management and analysis for gene expression arrays”
Nature Genetics 20: 19-23, 1998] http://www.nhgri.nih.gov/DIR/LCG/15K/HTML/ng_paper.html Related (or equivalent?) term genome expression guilt by association method: For
assessing gene function, although not logically rigorous, the utility has
been demonstrated, as genes already known to be related do, in fact, tend
to cluster together based on their experimentally determined expression
patterns. The approach is made more systematic and statistically
sound by calculating the probability that the observed functional distribution
of differentially expressed genes could have happened by chance. [David
J. Lockhart & Elizabeth A Winzeler “Genomics, gene expression and DNA
arrays” Nature 405: 827-836 June 15, 2000 influence-based data mining: Algorithms & data
management glossary Laser Capture Microdissection: Cell biology
glossary mRNA expression: If messenger RNA
is only an intermediate on the way to production of the functional protein
products, why measure mRNA at all? One reason is simply that protein-
based
approaches are generally more difficult, less sensitive and have a lower
throughput than RNA- based ones. But more importantly, mRNA levels are immensely
informative about cell state and the activity of genes, and for most genes,
changes in mRNA abundance are related to changes in protein abundance.
[David J. Lockhart & Elizabeth A Winzeler “Genomics, gene expression
and DNA arrays” Nature 405: 827-836 June 15, 2000] Related (equivalent?)
term RNA expression metabolic profiling: Metabolic Profiling Dec. 3-4, 2001 Chapel Hill, NC
See also Functional genomics glossary metabolite expression: The availability of expression data is expected
to have a significant impact on the understanding of basic cellular processes
and the various mechanisms by which cells control these processes. Conversely,
the interpretation of expression measurements often requires knowledge about
biological networks. We have built upon the PathDB project ( http://www.ncgr.org/pathdb/) to create a database and tools for constructing, visualizing, and
analyzing cellular networks. This system is being used to interpret large- scale
gene, protein, and metabolite expression data through an integration system (ISYS)
synchronized with other publicly available databases and tools. Jeffrey
Blanchard "A Platform for the Interpretation of Gene, Protein, and
Metabolite Expression Data in the Context of Cellular Interactions" Metabolic Profiling Dec. 3-4, 2001 Chapel Hill, NC metabolite systems biology: An important part of metabolic
system biology is focussed on the profiling of body fluids in terms of small
molecules. This enables the integration of knowledge bi- directional from the
genome as well as the metabolome side. This gives a tremendous clearer
view on all aspects of importance not the least by starting up front by disease
phenotyping and integrating all aspects in target validation. Jan van der
Greef "Metabolite Systems Biology: A New Vision on Drug Discovery" Metabolic Profiling Dec. 3-4, 2001 Chapel Hill, NC molecular profile, molecular profiling: A set of molecules
in a particular cell or tissue type that exist within a range of values
that are distinct from those in other cell or tissue type that exist within
a range of values. Gene- transcript profiles are particularly appealing
because RNA transcripts represent the primary output of the genome …. This
technique, sometimes referred to as transcript imaging, has been used to
identify genes that vary between diseased and healthy tissues. Although
large changes in expression often attract our greatest attention, subtle
changes can be highly significant…Currently, the significance of the vast
majority of gene expression changes remains unknown … a small change in expression
level could be a valuable diagnostic and prognostic indicator, provided
that it can be accurately detected. [G Zweiger “Knowledge discovery in gene-
expression- microarray data” Trends in Biotechnology 17: 429-436 Nov.
1999] Related terms transcript profile, transcript profiling. CGAP [Cancer Genome Anatomy Project) Molecular
Profiling Initiative, National Cancer Institute http://cgap.nci.nih.gov/ overexpression, underexpression:
Comparison of expression levels of normal tissues with diseased tissue
may be useful for prognostics. Overexpression of a gene can be used
to produce proteins on an industrial scale. pathways
databases: : Electronic databases
of pathway information are currently limited in scope, computability, or
both. A major focus of infrastructure development to support large- scale
gene expression studies will be in the area of electronic biological pathway
databases and resources. [D Bassett et al “Gene expression informatics
– it’s all in your mine” Nature Genetics 21 (1supp): 51-56 Jan 1999]
Related term pathways Functional
Genomics, pattern recognition: Algorithms
glossary post hoc testing: The need for post hoc testing deserves special
mention. Because arrays measure a large number of genes simultaneously and
independently, false positives can occur. With false positives, certain genes’
expression appears to change, but the change is a not a result of underlying
biology but random chance. This phenomenon is especially common in biological
systems in which the changes are small in magnitude. The smaller the magnitude
of the change seen on a hybridization array, the more likely that it is a
spurious result. [CHI Microarrays] Related term statistical
analysis. profile: A table that lists the frequencies of each amino acid in each position of
protein sequence. Frequencies are calculated from multiple alignments of sequences containing a domain of interest
[NCBI Bioinformatics] How does this relate to the other profiling terms? Narrower terms clinical profiling, expression profiling,
expression profiling - sensitivity, gene expression profiling, genetic profiling,
genomic profiling, molecular profile, protein expression profiling, tissue
profiling, transcript profiling. protein and mRNA data: Proteomics glossary protein expression: One of the key challenges in functional genomics
today is the assessment of protein expression in the cell. Changes in protein
expression in response to disease or environment may provide valuable clues as
to which protein may serve as therapeutic targets. Because of the
technical difficulties in obtaining accurate information on protein levels,
researchers have relied on mRNA expression as an approximation. [CHI
Summit Proteomics] Protein expression analysis is undergoing a technological revolution, which
will change the fundamental nature of the data available. ... Current methods
for measuring protein expression are very different from those for measuring
gene expression. Typically, 2D gels are used to separate the proteins from one
another, and mass spectrometry (MS)
is then applied to identify the proteins. MS provides remarkably specific
identification of protein fragments, based on their masses. The masses are then
compared with lists of computed masses for identification. More and more groups
are now seeking to bypass 2D gels, using combinations of protein chips,
liquid chromatography, capillary electrophoresis, and mass spectrometry for
protein analysis. [CHI Bioinformatics] Great anticipation surrounds the area
of protein expression analysis. Currently, these studies use difficult-
to- standardize 2D gels and expensive mass
spectrometry. [CHI Target Validation] Protein expression, as monitored
by in situ cellular and subcellular localization, has become
exceedingly important in the post genome sequencing era. Immunohistochemistry,
coupled with traditional molecular and biochemical techniques, continues to be a
powerful tool for studying gene expression. [Promega eNotes, 2000-2001] http://www.promega.com/enotes/features/fe0008a_tabs.htm The importance
of the protein- based methods is that they measure the final expression
product rather than an intermediate. In addition, some of them enable the
detection of post- translational protein modifications (for example, phosphorylation
and glycosylation) and protein complexes, and in some cases, yield information
about protein localization … There is no question that protein - and
RNA- based
measurements are complementary, and that protein- based methods are important
as they measure observable that are not readily detected in other ways.
[David J. Lockhart & Elizabeth A Winzeler “Genomics, gene expression
and DNA arrays” Nature 405: 827-836 June 15, 2000] Identifying and quantifying the proteins
expressed … Levels of protein(s) in a biological sample (including gene
fraction studies). Area of great commercial interest [CHI Proteomics] protein expression profile, protein expression profiling: Similar to gene expression profiling,
protein expression can also be profiled using a two- color assay. This assay
provides an indication of the relative levels of protein expression between two
different conditions, whether they are disease vs. health, tissue vs. tissue,
or normal vs. drug treated. The antibodies can be used to tag the profiled
proteins, or the proteins themselves can be hapten derivatized, which in
turn become targets for the immuno- RCA signal amplification complex.
Hapten derivatization of the profiled proteins is one way to make this a
universal assay. [CHI Summit Proteomics] The vast number of candidate proteins generated
from genomics programs is creating enormous opportunities for biologists.
However, efficient and rapid expression of genes in homologous and heterologous
expression systems and rapid purification steps are major bottlenecks.
The practical and cost- effective expression of these novel proteins in
amounts large enough to allow for their proper characterization and evaluation
and, finally, for the scale- up for large- scale production of these proteins
presents many difficulties. Protein
Expression: PepTalk Jan. 7- 8, 2002 * San Diego CA. The expression pattern of a protein. Related (equivalent?) term protein profiling. protein
profiling: Allows one to
find differences in sample spectra very quickly using a small amount of
material. When those differences are noted, one may proceed to identify and
purify larger amounts of material using other types of array. This material can
then be used to characterize the protein and assays can be developed for
research or diagnostic purposes. Protein profiling is typically used for target
discovery, toxicological studies or disease marker discovery (Wright et al.
2000; Paweletz et al. 2000). [CHI Summit Proteomics] Related
(equivalent?) term protein
expression profiling. quantitative RT-PCR reverse transcription- polymerase
chain reaction QRT- PCR: Gene
amplification & PCR glossary Related term differential display. quantum resonance interferometry: Expression amplification middleware for enhancing the detection and quantitation of hybridized microarray signals by orders of magnitude over current techniques is presented. The technological principle underlying quantum resonance interferometry is analogous to speckle interferometry and active radar imaging, which have enabled dramatic improvements in ultraweak signal imaging and spectral informatics over the past decade. Specifically, gene expression amplification is achieved by inducing "interference" between a mathematically transformed, hybridized, digitized microarray output and an external designer stimulus. In a molecular diagnostic context, the external synthetic stimulus is designed based on a mutation or a target sequence of interest. Alternately, in a gene expression application for drug target discovery, the microarray "inherent noise response" statistics are used to
construct the external synthetic stimulus. This presents an attempt to get an over 100- to
10,000- fold quantitative improvement in detection sensitivity over classic
state- of- the- art bioinformatics. The resulting enhancement is enabling to microarray-based drug target discovery and diagnostic applications. Expression detection performance results comparing classic bioinformatics techniques and quantum interferometry will be presented for several classes of standard and spotted arrays.
Dr. Sandeep Gulati, ViaLogy Corp. Integrative
Bioinformatics: High-Throughput Interpretation of Pathways and Biology
Jan. 16-18, 2002 Zurich, Switzerland RAGE Random Activation of Gene Expression: We have developed a
proprietary technology, RAGE (Random Activation of Gene Expression), that we
believe provides us with the unique ability to express protein from virtually
any gene in the human genome, without requiring either the isolation of
individual genes or any prior knowledge of gene sequence, function or normal
expression characteristics. RAGE
enables us to rapidly survey the entire human genome for proteins with specific
biological functions and to quickly and accurately correlate protein function
with gene structure, addressing one of the most significant bottlenecks in
functional genomics. We
efficiently create comprehensive, genome- wide protein expression libraries that
can be used for many different applications, such as functional characterization
of expressed proteins, generation of cell lines expressing validated drug
targets, manufacturing of established therapeutic proteins and gene discovery. [Athersys,
Inc. website] http://www.athersys.com/products/rage.html RNA expression: The focus of most
current array based studies is the monitoring of RNA expression levels.
The tools are most comprehensive for the yeast Saccharomyces cerevisiae…Yeast
geneticists have recently [Jan 1999] begun reporting global expression
studies of such fundamental processes as mitosis and meiosis. The
tools are also quite powerful for mammalian genomes, albeit with room for
improvement. [Eric Lander “Array of hope” Nature Genetics 21 (1s): 3-4 Jan
1999] Related (equivalent?) term mRNA expression reverse transcription: Sequences,
DNA & beyond SAGE Serial Analysis of Gene Expression:
A method of gene expression analysis involving reverse transcription, restriction
enzyme mediated digestion of oligonucleotides, ligations and PCR. Specifically,
SAGE converts polyadenylated mRNA into cDNA by reverse transcription. Oligonucleotide
"tags" of 10-14 base pairs are then hybridized to the cDNA and reduced
by restriction enzymes. The tags are then ligated to form concatemers that
are amplified by PCR and then cloned and sequenced. The number of tags
present indicates the prevalence of the gene, a powerful tool for gene
discovery, but ill suited for high throughput. [CHI Gene Expression] SAGE homepage http://www.sagenet.org sequential regulation: Correlated changes in protein expression.
[CHI Proteomics] standards, gene expression: Microarrays glossary statistical analysis, expression data: Still at an early stage of
development. See data analysis Microarrays glossary subtraction cloning: Uses competitive
hybridization of nucleic acids from two different samples to selectively
remove common expressed sequences, What remains are those sequences uniquely
expressed in one sample or the other. [CHI Gene Expression] subtractive hybridization: Method by which genes expressed in a
tissue-specific manner can be enriched for cloning. [Space Studies Board "A
Strategy for Research in Space Biology and Medicine in the New Century"
glossary, 2001] http://www.nationalacademies.org/ssb/csbmapb.htm#s TOGA Total Gene Expression Analysis:
An automated hybrid of SAGE and differential display, promises to completely
elucidate gene expression patterns for a given tissue or cell. It requires
a complex series of steps involving multiplex PCR, cDNA cloning, in
vitro transcription, cDNA construction, sequencing gel analysis, and
quantification. [CHI Gene Expression] tissue profile, tissue profiling:
Compares
gene expression in diseased and normal tissues. Useful in the target validation process. transcript: An mRNA molecule that
encodes a protein. [Schlindwein] Narrower term In-depth alternative
transcript transcript arrays: Microarrays glossary transcript expression: Advances
[in the study of gene transcription] have not been matched by an
understanding of the transcripts that are actually expressed under different
conditions in cells, tissues, and organisms. The development of methods
to visualize gene expression by hybridization of DNAs carried on chips
promised to help correct that ignorance … In the past few years, the number
of such proteins [lacking a particular transcription associated protein]
has greatly proliferated … and this has been reflected in a burgeoning and
confusing literature….[some results suggest] control of the activity of
individual transcription components – by which extracellular and intra-
cellular
events can affect gene expression. [Roger Brent ‘Learning to think about gene
expression data” Current Biology 9: R338-341 May 6 1999] transcript imaging: See molecular profiles/ molecular profiling. transcript profile, transcript profiling: Four
characteristics of the regulation of gene expression at the level of transcript
abundance account for the great value and appeal of genome- wide surveys
of transcript levels … DNA microarrays make it easy … the tight connection
between the function of a gene product and its expression pattern … promoters
function as transducers … Thus, as we learn what information is transduced
by the promoter of each gene, we can begin to read this information from
the profile of transcripts. [Patrick O. Brown “Exploring the new world of the genome”
Nature Genetics 21 (1s): 33-37 1999] A pharmacogenomic
application that might enable drugs or other treatments to be tailored
to narrowly defined patient groups, or to be excluded from patients with
a high likelihood of responding adversely. [Zweiger G. “Knowledge discovery
in gene- expression microarray data.” Trends in Biotechnology. November
1999;17:429-436.] Related term molecular profile, molecular profiling transcription: The process by which the genetic information encoded
in a linear sequence of nucleotides in one strand of DNA is copied into
an exactly complementary sequence of RNA. [IUPAC Biotech] Can be used to find disease related genes to discover pathways, leading to drug target identification
and test the effect of
drugs on gene expression (which can warn of potential side effects). Useful in
toxicology and pharmacogenomics
studies. More under transcription: Sequences, DNA
& beyond transcription factors: Sequences, DNA
& beyond transcription machinery: Sequences, DNA
& beyond transcriptional repression: A network of transcriptional repressors keeps the genome in a quiescent state, unless directed otherwise by transcriptional activators. We have employed DNA microarray analysis in the yeast Saccharomyces cerevisiae to peel back layers of repression and reveal the mechanisms by which each repressor exerts control over gene expression. Surprisingly, our findings indicate that chromatin is highly accessible and that a significant amount of global repression is targeted directly at the general transcription machinery by preventing it from assembling at permissive chromatin.
[Dr. Frank Pugh, Pennsylvania State Univ. "Unraveling Genomewide Networks of Transcriptional Repression"
Integrative
Bioinformatics:
High-Throughput Interpretation of Pathways and Biology Jan. 16-18,
2002 Zurich, Switzerland transcriptome, transcriptomics: Omes & omics
glossary translatome: Omes & omics glossary underexpression: See under overexpression;
underexpression. upregulation: Process
that increases ligand/receptor interactions due to an increase in the number
of available receptors. [MeSH] whole genome expression: Narrower terms genome expression, global gene
expression. IUPAC definitions are reprinted with the
permission of the International Union of Pure and Applied Chemistry. Bibliography [CHI Gene Expression] Cambridge
Healthtech Institute, Kent Vrana and Williard Freeman, Genomic-Scale
Gene Expression Analysis: Advancing from DNA to Disease, Report 6,
Nov. 2000. http://www.chireports.com/content/reports/multiplex.asp Alpha
glossary index |