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Biopharmaceutical Expression, genes & proteins glossary & taxonomy
Evolving terminology for emerging technologies

Suggestions? Comments? Questions? Mary Chitty
Last revised May 28, 2014
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This Expression glossary seems to have a number of terms which could be synonymous (i.e. expression, gene expression, various profiling terms) Are there subtle differences and/ or ambiguities?

alternative transcripts:   Demands on Microarray Design for the evaluation of gene regulation,  Genomatix 

Google = about 959 Aug. 12, 2002; about 4,610 Aug. 22, 2003; about 11,500 Apr. 27, 2005, including academic transcripts.

analysis - gene expression: 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.  Google = about 336,000 Aug. 12, 2002; about 592,000 Aug. 22, 2003  Related terms: post hoc testing, statistical analysis;  guilt by association Algorithms glossary cluster analysis, pattern recognition;  Microarrays glossary data analysis, standards

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. Google = about 38,000 Aug. 12, 2002; about 130,000 Aug 22, 2003  [analysis "protein expression"]

artificial transcription factors: Regulated gene expression is critical for cellular existence, and a disruption in the regulatory network can result in disease or death. Therefore, a goal of primary importance in the scientific community has been to discover methods of reprogramming gene expression in diseased cells while leaving normal cells unaffected. Our understanding of transcription, an early step in gene expression, has now reached a sufficiently sophisticated level to allow us to tackle this challenge from a chemical perspective. Dendritic and polymeric structures designed to functionally mimic the protein participants in activation and repression of transcription will be examined through in vitro assays and cell culture experiments. Organic synthesis will play a critical role in this effort. By varying the synthetic approaches to the artificial transcription factors, their overall function as activators and/ or repressors can be controlled and important characteristics such as cell membrane permeability and tissue- type specificity can be addressed. Anna K. Mapp "Chemistry at the Univ. of Michigan, 2001  Google = about 49  Aug. 12, 2002; about 347 Aug. 22, 2003  Broader term: transcription factor

bacterial protein expression systems: are popular because bacteria are easy to culture, grow fast and produce high yields of recombinant protein. However, multi-domain eukaryotic proteins expressed in bacteria often are non-functional because the cells are not equipped to accomplish the required post-translational modifications or molecular folding. Also, many proteins become insoluble as inclusion bodies that are very difficult to recover without harsh denaturants and subsequent cumbersome protein-refolding procedures. Overview of Protein Expression Systems, Thermo Scientific Pierce

basal transcription factors: Typically defined as the minimal complement of proteins necessary to reconstitute accurate transcription from a minimal promoter (such as a TATA element or initiator sequence). They are distinct from the regulatory transcription factors, which bind to sequences farther away from the initiation site and serve to modulate levels of transcription. This regulation presumably occurs through interactions between the regulatory and basal transcription factors, although there is a great deal of controversy about the identity of the regulatory factors' "target(s)" The basal transcription complex assembles through an extensive series of protein-protein interactions. Although the basal factors can assemble on the promoter in a step- wise manner in vitro, there is some evidence that many of the factor interactions can occur in the absence of DNA and that some of the factors may pre- assemble into a "holoenzyme".  Steve Buratowski, Basal Transcription Factor Information, Harvard Medical School, 1999]

Google = about 795 Aug. 12, 2002; about 2,070 Aug. 22, 2003

biological networks:  We are amongst the first groups to describe how many weak functional genomic features could be systematically integrated with data mining techniques to predict protein networks (comprising protein interactions and other functional linkages). Some of the features integrated were obviously related to protein interactions (e.g. expression correlations) but many others such as (e.g. essentiality) were less so. We have had a number of localization and interaction predictions experimentally verified. In more recent work, we were able to calibrate the degree to which the data quality and the specific mining approach is associated with the strength of the predictions. In addition, we have studied the structure of protein networks, both on a large-scale in terms of global statistics (e.g. the diameter) and on a small-scale in terms of local network motifs (e.g. hubs). In particular, we have correlated network hubs with gene essentiality. Most importantly, we were the first to study the dynamics of regulatory networks. This allowed us to discover changing transient hubs and systematic patterns of connectivity rewiring in the yeast regulatory network. We were able to show for the first time that network dramatically changes in different conditions. Gerstein Lab Publications, Yale University, 2007   Google = about 4,740 Aug. 22, 2003; about 293,000 June 11, 2007

cell expression profiles: Cell biology glossary  Google = about 31 Aug. 12, 2002; about 45 Aug. 22, 2003

cell- specific gene expression: The essence of multicellularity is the ability to express only certain portions of the genome in particular cells at particular times. This is done by the synthesis and assembly of transcription factors that turn on (and off) specific genes as required. John W. Kimball, Detecting Cell Specific Gene Expression, Kimball's Biology Pages, 2005   Google = about 681 Aug. 12, 2002; about 1,660 Aug. 22, 2003; about 5,120 Apr. 27, 2005; about 66,000 June 11, 2007

clinical profiling - 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 significant potential markets for diagnostics, choosing appropriate therapies, and ongoing monitoring.   Google = about 15 Aug. 12, 2002; about 26, Aug. 22, 2003

conditional gene expression: When gene expression is activated or suppressed at will.  Google = about 236 Aug. 12, 2002; about 558 Aug. 22, 2003, about 21,800 Sept 7, 2007

co-regulation - expression: 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.  Google = about 1,420 Aug. 12, 2002; about 1,930 Aug. 22, 2003

differential display: A theoretically powerful approach in which researchers use multiplex quantitative reverse transcription- polymerase chain reaction (QRT- PCR) to amplify – and illuminate – differences in gene expression between healthy and diseased tissue or between treated versus nontreated tissue. ... a single gel can "sample" a significant portion of the expressed complement of genes in a given tissue, under different physiological/ pharmacological conditions.  This technology has not been universally successful and has not gained widespread acceptance due to technical complexities.  Differential display is an attractive approach, because it (a) searches for differences in gene expression in the absence of preconceived biases; and (b) does not require extensive preexisting knowledge concerning genes of interest. As such, this technique is especially useful for identifying novel gene- disease associations.   Google = about 22,700 Aug. 22, 2003; about 692,000 June 11, 2007  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

differential protein expression profiling:   Google = about 24 Aug. 22, 2003; about 3,080 June 11, 2007

DNA profiling techniques  Wikipedia  notes "not to be confused with full genome sequencing"  accessed Feb 24 2011 
wikipedia Category:DNA_profiling_ techniques

downregulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. MeSH, 2002
Wikipedia Downregulation and upregulation

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  Google = about 5 Aug. 12, 2002; about 53 Aug. 22, 2003, about 64 Sept 7, 2007

epigenetic imprinting: A key component of future genomic research and drug development will be the study of epigenetic imprinting (drug- or environment-induced changes in gene expression) indicative of disease and/or pharmacological or environmental exposure.  Google = about  48 Aug. 12, 2002; about 101 Aug. 22, 2003; about 619 June 11, 2007

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 databases Databases & software directory

expression genomics: Genome-wide expression microarray studies have revealed that the biological and clinical heterogeneity of breast cancer can be partly explained by information embedded within a complex but ordered transcriptional architecture. Comprising this architecture are gene expression networks, or signatures, reflecting biochemical and behavioral properties of tumors that might be harnessed to improve disease subtyping, patient prognosis and prediction of therapeutic response. Miller, Lance D, Liu, Edison T, Expression genomics in breast cancer research: microarrays at the crossroads of biology and medicine Breast Cancer Research 2007, 9:206 doi:10.1186/bcr1662, March 2007  Google = about 1,330 Aug. 22, 2003; about 39,400 June 11, 2007

expression mapping: Maps genomic & genetic  Google = about  1,130 Aug. 12, 2002; about 2,390 Aug. 22, 2003; about 68,900 June 11, 2007
expression maps: Maps genomic & genetic  Narrower terms: gene expression maps, expression imbalance map, protein expression map, self- organizing maps, transcript maps Related terms: EST maps, genome control maps 
Google = about 452 Aug. 12, 2002; about 733 Aug. 22, 2003; about 23,000 June 11, 2007 

expression pharmacogenomics: Pharmacogenomics glossary  Google = about 42 Aug. 12, 2002; about 58 Aug. 22, 2003; about 218 June 11, 200, about 584 Apr 6, 2009
expression product: Related term Gene definitions gene product  
Google = about  1,290 Aug. 12, 2002; about 2,680 Aug. 22, 2003, about 91, 200 Apr 6, 2009

expression profiling:  In an attempt to avoid expensive late-stage candidate failures, pharmaceutical companies apply increasingly stringent compound characterization and selection processes. Gene expression profiling is becoming increasingly adopted in small molecule drug development programs to characterize pharmacological and toxicological activity.  

Refers to the expression values for a single gene across many experimental conditions, or for many genes under a single condition. In the terminology of cluster format [Algorithms glossary], the first case amounts to looking at a row of the data table, and the second case a column.  Google = about 14,200 Aug. 12, 2002; about 51,500 Aug. 22, 2003; about 120,000 Sept. 16, 2004, about 1,470,000 Apr 6, 2009  Narrower terms: gene expression profiling,  protein expression profiling, transcript profiling.  Related terms: gene expression, molecular indexing, protein expression, RNA expression, transcript expression
PEPR Public Expression Profiling Resource
, Children's National Medical Center, Microarray Center

expression 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

Large- scale measurements of protein expression. Google = about 668 July 10, 2002; about 1,250 Aug. 22, 2003

expression systems:  include cell free, transient, microbial, stable cell lines, mammalian cell lines, plants and transgenic animals.

expression technologies: Chromatography & electrophoresis, Gene amplification & PCR  Microarrays have been a breakthrough technology for studying gene expression. 
Google = about 1,140 Aug. 12, 2002; about 1,630 Aug. 22, 2003, about 42,600 Sept 7, 2007 
Narrower terms: differential display, RAGE, SAGE, subtraction cloning, TOGA.

gene clustering: Cluster methods include: finding genes similar to the current selected gene within a "distance" threshold; K-means-like clustering where you specify a seed gene and the number of clusters; and hierarchical clustering with clustergram and dendrogram graphics.  National Cancer Institute, MicroArray Explorer   Related terms: Algorithms glossary cluster analysis, hierarchical clustering, k- means clustering, self organizing maps  Google = about 604 Aug. 12, 2002; about 1,630 Aug. 22, 2003
Eisen Lab
, Lawrence Berkeley National Lab, US

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 phenotypic manifestation of a gene or genes by the processes of gene action. MeSH, 1990

The transcription of a gene and its processing to yield a mature messenger RNA (mRNA). (Note that in proteomic studies, the same term also includes the translation of the mRNA to produce a functional protein.) In studies of differential gene expression, one looks for genes whose expression levels differ significantly under different experimental conditions, for example in normal versus diseased states or in untreated versus treated subjects. This application is perhaps the most obvious use of microarrays. 

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   
Google = about 592,000 Aug. 12, 2002; about 1,100,000 Aug. 22, 2003 
Broader terms: expression, genome expression.
Glossary of gene expression terms
, Wikipedia 
Trends and Challenges in Gene Expression Data Collection and Analysis:
Commentary from Gene Logic, CHI's GenomeLink 16.2 
Gene expression databases Databases & software directory

gene expression informatics: "Gene expression informatics- it's all in your mine" Douglas E. Bassett Jr. , Nature Genetics 21(1 Supplement): 51- 55, Jan 1999.  Google = about 262 Aug. 12, 2002; about 416, Aug. 22, 2003  Related terms: gene expression database mining; Microarrays data analysis - microarrays

gene expression profiling: Biology is not static – neither are the tools and technologies that support genomic discovery for basic and pharmaceutical research.  Gene expression profiling is preferred, providing common language for finding relationships between health and disease; genetic changes as a result of therapy; markers for toxicology and drug safety; and even potentially leading to personalized medicine.   Additionally, it may be possible to capture these revealing expression profiles with as few as a thousand transcripts. Advances in Gene Expression Profiling: Technologies Transcripts Therapies  Nov 2009 Philadelphia PA  order CD

The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. MeSH, 2000

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.  Google = about 7,630 Aug. 12, 2002' about 31, 500 Aug. 22, 2003, about 4,610,000 Apr 6, 2009 Related terms: expression profile, expression profiling. Related term protein expression

gene expression regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action at the level of transcription or translation. These processes include gene activation and genetic induction. MeSH, 1981  Google = "gene expression regulation" about 2,900 "gene expression" regulation about 230,000 Aug. 12, 2002; "gene expression regulation" about 62,900 Aug. 22, 2003; about 212,000 May 25, 2005  Related terms Omes & omics glossary regulome, regulomics; Proteins glossary protein regulation; Proteomics glossary: protein- protein interactions
Gene regulation in eukaryotes
, Kimball's Biology Pages
Gene regulation in prokaryotes: See Gene definitions: operon

gene shaving: A statistical method, which ... 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  Google = about  377 Aug. 12, 2002; about 611 Aug. 22, 2003, about 3,930 Apr 6, 2009

gene silencing: Gene definitions Has effect upon gene expression  Google = about 11,000 Aug. 12, 2002; about 26,700 Aug. 22, 2003, about 1, 101,000 Apr 6, 2009

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. Oxford English Dictionary

Sometimes known as genetic fingerprinting. [Oxford Biochem] Google = "genetic profiling" about 1,820; "genetic fingerprinting" about 4,960  Aug. 12, 2002; "genetic profiling" about 3,800; "genetic fingerprinting" about 6,400  Aug. 22, 2003 

genome control maps: Maps & mapping glossary  Google = about 12 Aug. 12, 2002; about 14, Aug. 22, 2003

genome expression,: Gene expression at the whole- genome level. Related term global gene expression. Or are these equivalent? Google = about  2,400 Aug. 12, 2002; about 4,770 Aug. 22, 2003, about 71,100 Apr 6, 2009

genomic profiling: Refers to testing for genotypes at multiple loci for susceptibility to common diseases and the subsequent targeting of behavioral and medical interventions. CHA Cambridge Healthtech Advisors, Clinical Genomics: The Impact of Genomics on Clinical Trials and Medical Practice report, 2004

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]  
Google = about 625 Aug. 12, 2002; about 989 Aug. 22, 2003; about 2,580 June 21, 2004, about 53,600 Apr 6, 2009

global gene expression: 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 
Google = about 2,060 Aug. 12, 2002; about 6,210 Aug. 22, 2003; about 13,600 June 10, 2004, about 177,000 Apr 6, 2009 
Related (or equivalent?) term: genome expression

global regulators- expression: The loosely- defined term "global regulator" refers to a relatively small number of genes whose products have a wide- ranging influence on the state of the cell. One mechanism of action of these regulators is that their products bind the DNA slightly upstream of the coding region of the gene whose expression they influence. Thus there is information in both gene expression and genome sequence measurements regarding the identities of the global regulators. I will discuss a graph- structured probability model for identifying global regulators. Kerby A Shedden, Univ. of Michigan "Two Problems in Genomics that can be Addressed by Statistical Modeling and Simulation" UCLA Dept. of Statistics Department Seminar, Nov. 6, 2001

Google = about 378 Aug. 12, 2002; about 1,150 Aug. 22, 2003; about 3,180 June 10, 2004 Related terms: mixed cell populations- expression signals Pharmacogenomics glossary

in silico transcriptomics : Omes & omics glossary  Google = about 12 Aug. 12, 2002; about 14, Aug. 22, 2003, about 138 Apr 6, 2009

in vitro (Cell-free) Protein Expression: Cell-free protein expression is the in vitro synthesis of protein using translation-compatible extracts of whole cells. In principle, whole cell extracts contain all the macromolecules components needed for transcription, translation and even post-translational modification. These components include RNA polymerase, regulatory protein factors, transcription factors, ribosomes, and tRNA. When supplemented with cofactors, nucleotides and the specific gene template, these extracts can synthesize proteins of interest in a few hours. Overview of Protein Expression Systems, Thermo Scientific Pierce

high- throughput protein expression: One of the key steps of structural genomics and proteomics is high-throughput expression of many target proteins. Gene cloning, especially by ligation- independent cloning techniques, and recombinant protein expression using microbial hosts such as Escherichia coli and the yeast Pichia pastoris are well optimized and further robotized. Cell- free protein synthesis systems have been developed for large- scale production of protein samples for NMR (stable- isotope labeling) and X-ray crystallography (selenomethionine substitution). Protein folding is still a major bottleneck in protein expression. Cell- based and cell- free methods for screening of suitable samples for structure determination have been developed for achieving a high success rate. S. Yokoyama, Protein expression systems for structural genomics and proteomics, Current Opinion in Chemical Biology 7(1): 39-43, Feb. 2003  
Google = about 574  Aug. 22, 2003, about 6,660 Apr 6, 2009

in vivo Protein Expression: Traditional strategies for recombinant protein expression involve transfecting cells with a DNA vector that contains the template and then culturing the cells so that they transcribe and translate the desired protein. Typically, the cells are then lysed to extract the expressed protein for subsequent purification. Both prokaryotic and eukaryotic in vivo protein expression systems are widely used. The selection of the system depends on the type of protein, the requirements for functional activity and the desired yield. Overview of Protein Expression Systems, Thermo Scientific Pierce

layered expression scanning: uses a layered array of capture membranes coupled to antibodies or DNA sequences to perform multiplex protein or mRNA analysis Englert CR, Baibakov GV, Emmert- Buck MR, "Layered expression scanning: rapid molecular profiling of tumor samples" Cancer Research 60(6): 1526- 1530,  Mar. 15, 2000    Google = about 21 Aug. 12, 2002; about 54 Aug. 22, 2003  Related terms: expression microdissection; Cell biology glossary Laser Capture Microdissection LCM

mammalian in vivo expression systems: usually produce functional protein, but the yield is low, cost of production is high and mammalian cell culturing is time-consuming. In addition, in vivo systems are not conducive to either high throughput protein synthesis or expression of proteins that are toxic to host cells. Overview of Protein Expression Systems, Thermo Scientific Pierce

mesoscopic biology: looks between the macroscopic and microscopic (single cell) realms. Using quantitative RT-PCR, and sampling variable numbers of cells, we were able to demonstrate that steady state gene expression does, in fact, obey Poisson statistics (Mar et al., 2006Go). The beauty of this approach is that it can provide experimental measurements even for genes expressed at very low levels. It further suggests that other stochastic events occurring in single cells, even complex interactions in pathways, may reveal themselves through the analysis of samples of mesoscopic size. John Quackenbush, Extracting biology from high dimensional data, First published online April 20, 2007 Journal of Experimental Biology 210, 1507-1517 (2007) Published by The Company of Biologists 2007 doi: 10.1242/jeb.004432 

mesoscopic expression: John Quackenbush 

metabolic engineering, metabolic fingerprinting, metabolic pathways: Metabolic engineering glossary
metabolic phenomics: Omes & omics glossary 
Google = about 45 Aug. 12, 2002; about 65 Aug. 22, 2003, about 310 Apr 6, 2009
metabolic profiling: Metabolic engineering glossary 
Google = about 1,570 Aug. 12, 2002; about 2,900 Aug. 22, 2003, about 57,300 Apr 4, 2009
metabolite, metabolite expression,  metabolite profiling, metabolism, metabolite systems biology: Metabolic engineering glossary

metagenes: Aggregate patterns of gene expression (metagenes) that associate with lymph node status and recurrence, and that are capable of predicting outcomes in individual patients with about 90% accuracy. The metagenes defined distinct groups of genes, suggesting different biological processes underlying these two characteristics of breast cancer. E. Huang, Gene expression predictors of breast cancer outcomes, Gene expression predictors of breast cancer outcomes, Lancet 361(9369): 1590- 1596, May 10, 2003

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  Google = about  28,700 Aug. 12, 2002; about 125,000 Aug. 22, 2003

mRNA expression arrays: Messenger RNA expression arrays immobilize stretches of mRNA and are used to measure the concentration of mRNA species in a sample as a function of tissue type, cell cycle and other environmental conditions. Andrej Sali et. al,  From words to literature in structural proteomics, Nature 442 (6928): 13 Mar. 2003  Google = about 23 May 15, 2003; about 42 Aug. 22, 2003  Related terms: gene expression arrays, protein expression arrays; Are RNA expression arrays equivalent to mRNA expression arrays? 

molecular indexing:  A technique to select a subpopulation of cDNA by ligation of adapters to cDNA fragments digested by a class IIS restriction enzyme(s). By this technique, 3' end cDNA fragments are divided into 16 fractions by selective ligation of adapters and subsequent PCR amplification. Each fraction is used as a hybridization target for microarray hybridization. This fractionated target has a relatively lower nucleic acid complexity, including more fractions for rare transcripts, and is useful for their detection. "Microarray hybridization with fractionated cDNA: enhanced identification of differentially expressed genes" K. Sakai, H. Higuchi, K. Matsubara, K. Kato, Analytical Biochemistry 287 (1): 32- 37, Dec. 1, 2000 Google = about 88 Aug. 12, 2002; about 137 Aug. 22, 2003; about 341 Feb. 17, 2005, about 1,390 Apr 6, 2009  Related terms: differential display, expression profiling

molecular profiling: Drug & disease targets  Google = about 1,160 Aug. 12, 2002; about 7,660 Aug. 22, 2003, about 249,000 Sept 7, 2007, about 108,000 Apr 6, 2009 
Related terms: transcript profile, transcript profiling; Cell biology  cellular resolution, FACS, laser capture microdissection
CGAP [Cancer Genome Anatomy Project] Molecular Profiling Initiative,
National Cancer Institute

nucleome: -Omes & -omics glossary

overexpressed proteins: Are often insoluble, and can be recalcitrant to conventional solubilization techniques such as refolding. Directed evolution methods, in which protein diversity libraries are screened for soluble variants, offer an alternative route to obtaining soluble proteins. Recently, several new protein solubility screens have been developed that do not require structural or functional information about the target protein. Soluble protein can be detected in vivo and in vitro by fusion reporter tags. Protein misfolding can be measured in vivo using the bacterial response to protein misfolding. Finally, soluble protein can be monitored by immunological detection. Efficient, well- established strategies for generating and recombining genetic diversity, driven by new screening and selection methods, can furnish correctly folded, soluble protein. GS Waldo, Genetic screens and directed evolution for protein solubility, Current Opinion in Chemical Biology 7(1): 33- 38, Feb. 2003  Google = about 834 Aug. 22, 2003

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.  Google = overexpression about 74,200 Aug. 12, 2002; about 300,000 Sept. 16, 2004

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  Google = about  224 Aug. 12, 2002; about 253 Aug. 22, 2003; about 580 Sept. 16, 2004  Related terms: Metabolic engineering pathways   

phylogenomic profiling: Phylogenomics glossary

post hoc testing- expression: 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.  
Google = about  94 Aug. 12, 2002; about 578 Aug. 22, 2003 
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 correlation profiling:  Overcomes the problem in proteomics of distinguishing proteins that are part of a complex from contaminating proteins. This method could be applied to the analysis of any protein complex. For example, a team led by Matthias Mann, a professor in the department of biochemistry and molecular biology at the University of Southern Denmark in Odense, and Erich A. Nigg, director of the cell biology department at Max Planck Institute for Biochemistry in Martinsried, Germany, has applied the method to characterize the centrosome Nature, 426, 570 (2003)]. New proteomic method, Chemical & Engineering News, Dec. 4, 2003  Related/synonymous term: protein profiling

protein expression:  Protein expression refers to the way in which proteins are synthesized, modified and regulated in living organisms. In protein research, the term can apply to either the object of study or the laboratory techniques required to manufacture proteins. This article focuses on the latter meaning of protein expression. However, in practical terms, recombinant protein production depends on using cellular machinery. Overview of Protein Expression Systems, Thermo Scientific Pierce

Just because a gene is overexpressed doesn’t necessarily mean the protein will be. Sometimes we find the accompanying protein to be downregulated even though the gene is upregulated: That is because there are a lot of steps between gene expression and protein expression. Better Understanding of Diseases and Drug Targets Through Systems Biology: An Interview with N. Stephen Ober of Beyond Genomics, CHI's GenomeLink 17.2 

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     Google = about 69,100 Aug. 12, 2002; about 197,000 Aug. 22, 2003; about 2,680,000 June 11, 2007  Narrower terms: cell-free protein expression, difficult to express proteins, high- throughput protein expression

protein expression arrays: Microarrays glossary protein chips  Google = about 27 May 15, 2003; about 38 Aug. 22, 2003; about 54 June 10, 2004; about 3,450 June 11, 2007

protein expression profile: 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. 

The expression pattern of a protein. Related (equivalent?) term protein profiling.  Google = about 122 Aug. 12, 2002; about 396 Aug. 22, 2003; about 761 June 10, 2004; about 33,700 June 11, 2007, about 44,800 Apr 6, 2009

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).   Google = about  1,180 Aug. 12, 2002; about 2,840 Aug. 22, 2003; about 6,440 June 10, 2004; about 159,000 June 11, 2007, about 68,200 Apr 6, 2009  Related (equivalent?) term: protein expression profiling.

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  Google = about  5,370 Aug. 12, 2002, about 17,400 Aug. 22, 2003; about 868,000 June 11, 2007, about 1,420,000 Apr 6, 2009  Related (equivalent?) term: mRNA expression

RNA expression arrays: See mRNA expression arrays Google = about 41 May 15, 2003; about 44, Aug. 22, 2003, about 433 Apr 6, 2009

regulomics: The regulation of specific molecular interactions that determine gene expression. 

reverse transcription:  Sequences, DNA & beyond  Google = about 24,900 Aug. 12, 2002; about 109,000 Aug. 22, 2003

Serial Analysis of Gene Expression SAGE: SAGE is a sequence- based technology for gene identification and quantitation in which short (10-14 bp) sequences, called tags, are extracted from specific positions within a transcript. Many transcript tags are concatenated into a single molecule and then sequenced, revealing the identity of multiple tags simultaneously. The expression profile is then computed by counting the abundance of individual tags and identifying the gene corresponding to each tag. Among the purported advantages of SAGE are that it is highly sensitive and scaleable and that it detects all genes, including unknowns, and provides quantitative data.  Google = about 3,150 Aug. 12, 2002; about 6,910 Aug. 22, 2003, about 253,000 Sept. 7, 2007 Related term: RAGE  SAGE homepage

sequential regulation:  Correlated changes in protein expression.  Google = about  63 Aug. 12, 2002; about 140 Aug. 22, 2003

spatio temporal dynamics:  Bioinformatics glossary
standards - gene expression: Microarrays glossary 
Google = 21,500 about  Aug. 12, 2002; about 58,400 Aug. 22, 2003

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. The drawbacks of this approach are that it requires technical sophistication and is associated with an extremely low throughput rate for target identification.... On the positive side however, this approach does not involve proprietary technologies and is generally available to most investigators, and does not require a large infrastructure investment.   Google = about 207 Aug. 12, 2002; about 413, Aug. 22, 2003, about 4,510 Apr 6, 2009

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  Google = about 405 Aug. 12, 2002; about 7,650 Aug. 22, 2003

tissue profiling: Compares gene expression in diseased and normal tissues. Useful in the target validation process.  Google = about  57 Aug. 12, 2002; about 102, Aug. 22, 2003, about 4,770 Apr 6, 2009

trans-acting factors: Trans- acting factors functionally have two domains. One domain is required for the factor to bind to DNA, and the second domain is required for the activation of transcription. This was discovered by studying deletion mutants of the factors. Mutants factors were found that could bind DNA but could not activate transcription. Other experiments in which a hybrid protein consisting of the non- DNA binding segment of one trans- acting factor fused to the DNA- binding region of a second trans- acting activated transcription defined the second function of trans- acting factors. Phil McLean "Control of gene expression in eukaryotes" North Dakota State Univ. 1997  Google = about 3,050 Aug. 12, 2002; about 8,030 Aug. 22, 2003

trans-activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins. MeSH, 1990 Google = about 285 Aug. 12, 2002; about 8,390 Aug. 22, 2003

transcript: An mRNA molecule that encodes a protein. [Schlindwein]  Narrower term alternative transcript

transcript abundance:  Information about mRNA transcript abundance under different experimental conditions can be obtained from the analysis of EST sequences. If we assume that ESTs are randomly selected from non- normalised libraries, then the number of EST sequences representing each gene is directly proportional to the mRNA abundance in the tissue from which the library was constructed. Cogeme, UK  Google = about 3,210 Aug. 22, 2003, about 68,300 Apr 6, 2009  

transcript amplification: See under gene expression profiling 
Google = about 22 Aug. 12, 2002; about 114, Aug. 22, 2003, about 873 Sept 7, 2007

transcript arrays: Microarrays glossary Google = about 35 Aug. 12, 2002; about 64 Aug. 22, 2003, about 515 Sept 7, 2007

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  Google = about 642  Aug. 12, 2002; about 2,730 Aug. 22, 2003, about 57,700 Apr 6, 2009 Related term: tissue- specific/cell- specific gene expression

transcript imaging: See under molecular profiles/ molecular profiling  Google = about 225 Aug. 12, 2002; about 417, Aug. 22, 2003

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 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] 

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.]  Google = about 771 Aug. 12, 2002; about 1,900 Aug. 22, 2003, about 48,100 Apr 6, 2009  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:  Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. MeSH, 1977
Wikipedia   Google = about 72,600 Aug. 12, 2002; about 216,000 Aug. 22, 2003, about 2, 170,000 Sept. 7, 2007, about 12, 300, 000 Apr 6, 2009 
Narrower terms: artificial transcription factors, basal transcription factors, regulatory transcription factors

transcription machinery:  Sequences, DNA & beyond  Google = about  49,100 Aug. 12, 2002; about 91,500 Apr 6, 2009
transcriptome, transcriptomics:
Omes & omics glossary
Google = transcriptome about 8,120, transcriptomics about 1,770  Aug. 12, 2002; transcriptome about 32,600, transcriptomics about 4,130  Aug. 22, 2003
translatome: Omes & omics glossary 
Google = about  106 Aug. 12, 2002; about 69 Aug. 22, 2003, about 213 Apr 6, 2009

underexpression: See under overexpression; underexpression.

upregulation:  A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. MeSH, 2002   Google = about 19,300 Aug. 12, 2002; about 77,500 Aug. 22, 2003, about 2,760,000 Apr 6, 2009
Wikipedia Downregulation and upregulation

whole genome expression: The current excitement in bioinformatics - analysis of whole-genome expression data: how does it relate to protein structure and function? Mark Gerstein, Ronald Jansen. Current Opinion in Structural Biology 10:(5): 574- 584, 2000  Google = about 626 Aug. 12, 2002; about 1,810 Aug. 22, 2003, about 20,500 Apr 6, 2009  Narrower terms genome expression, global gene expression.

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.

Chipping Forecast III, Nature Genetics, 37 (65): June 2005 
Chipping Forecast II, Nature Genetics 32 (supp), 2002 
Science, Gene Expression and Function, Oct. 22, 2004 

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