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Accession number
An
identifier supplied by the curators of the major biological databases
upon submission of a novel entry that uniquely identifies that
sequence (or other) entry.
Active site
The
amino acid residues at the catalytic site of an enzyme. These
residues provide the binding and activation energy needed to place
the substrate into its transition state and bridge the energy barrier
of the reaction undergoing catalysis
Adenine
A
purine base found in DNA and RNA
Agents
Independent,
autonomous, software modules that can search the Internet for data or
content pertinent to a particular application, such as a gene,
protein, or biological system.
Agricultural
biotechnology (AgBio)
The
application of rDNA technology to agriculturally important plants and
organisms.
Algorithm
A
series of steps defining a procedure or formula for solving a
problem, that can be coded into a programming language and executed.
Bioinformatics algorithms typically are used to process, store,
analyze, visualize and make predictions from biological
data.
Alignment
The
result of a comparison of two or more gene or protein sequences in
order to determine their degree of base or amino acid similarity.
Sequence alignments are used to determine the similarity, homology,
function or other degree of relatedness between two or more genes or
gene products.
Allele
A
given form of a gene that occupies a specific position or locus on a
chromosome. Variant forms of genes occurring at the same locus are
said to be alleles of one another.
Alternative splicing
One
of the alternate combinations of a folded protein that are possible
due to by recombination of multiple gene segments during mRNA
splicing that occurs in higher organisms.
Alternative splice-form
One
of the possible alternate combinations of exons into a folded protein
that are possible by recombining multiple gene segments during mRNA
splicing in higher organisms.
Alu family
A
common set of dispersed DNA sequences found throughout the human
genome; each is about 300 bases long and they are repeated at least
500,000 times. Alu sequences are speculated to have originated from
viral RNA sequences that integrated into human DNA thousands of years
ago.
Amino acid
One
of the 20 chemical building blocks that are joined by amide (peptide)
linkages to form a polypeptide chain of a protein
Analogy
Reasoning
by which the function of a novel gene or protein sequence may be
deduced from comparisons with other gene or protein sequences of
known function. Identifying analogous or homologous genes via
similarity searching and alignment is one of the chief uses of
Bioinformatics. (See also alignment, similarity search.)
Annotation
A
combination of comments, notations, references, and citations, either
in free format or utilizing a controlled vocabulary, that together
describe all the experimental and inferred information about a gene
or protein. Annotations can also be applied to the description
of other biological systems. Batch, automated annotation of
bulk biological sequence is one of the key uses of Bioinformatics
tools.
Anticodon
The
triplet of contiguous bases on tRNA that binds to the codon sequence
of nucleotides on mRNA. Example: GGG codes for Glycine.
Antigen
Any
foreign molecule that stimulates an immune response in a vertebrate
organism. Many antigens are proteins such as the surface proteins of
foreign organisms.
Antisense
DNA
or RNA composed of the complementary sequence to the target DNA/RNA.
Also used to describe a therapeutic strategy that uses antisense DNA
or RNA sequences to target specific gene DNA sequences or mRNA
implicated in disease, in order to bind and physically inhibit their
expression by physically blocking them.
Assay
A
method for measuring a biological activity. This may be enzyme
activity, binding affinity, or protein turnover. Most assays utilize
a measurable parameter such as color, fluorescence or radioactivity
to correlate with the biological activity.
Assembly
Compilation
of overlapping sequences from one or more related genes that have
been clustered together based on their degree of sequence identity or
similarity. Sequence assembly may be used to piece together "shotgun"
sequencing fragments (see shotgun sequencing) based upon overlapping
restriction enzyme digests, or may be used to identify and index
novel genes from "single-pass" cDNA sequencing efforts.
Autoradiography
A
method used to locate radioisotope-labeled materials which have been
separated in gels or are present in blots. The location of the
radiolabeled material is determined by overlaying the test material
with a photographic film that is sensitive to the
radioisotope.
Bacterial
artificial chromosome (BAC)
Cloning
vector that can incorporate large fragments of DNA. (see
YACS)
Bacteriophage
A
virus that infects bacteria. The bacteriophage DNA has served as a
basis for cloning vectors, and is also utilized to create phage
libraries containing human or other genes.
Baculovirus
An
insect virus which forms the basis of a protein expression
system
Base
pair
A
pair of nitrogenous bases (a purine and a pyrimidine), held together
by hydrogen bonds, that form the core of DNA and RNA i.e the A:T, G:C
and A:U interactions.
Beta
sheet
A
three dimensional arrangement taken up by polypeptide chains that
consists of alternating strands linked by hydrogen bonds. The
alternating strands together form a sheet that is frequently twisted.
One of the secondary structural elements characteristic of
proteins.
Bioinformatics
The
field of endeavor that relates to the collection, organization and
analysis of large amounts of biological data using networks of
computers and databases (usually with reference to the genome project
and DNA sequence information)
Bivalent
Having
two binding sites; having 2 free electrons available for
binding.
Blunt-end (ligation)
The
joining of DNA fragments that contain no overhang at either end and
consequently no DNA bases available for hybridization (cf. sticky-end
ligation).
Carboxyl group
The
-COOH functional group, acidic in nature, found in all amino
acids
cDNA
(complementary DNA)
A DNA
strand copied from mRNA using reverse transcriptase. A cDNA library
represents all of the expressed DNA in a cell.
cDNA library
A set
of DNA fragments prepared from the total mRNA obtained from a
selected cell, tissue or organism.
Cell
The
basic unit of any living organism.
Cell Cycle
The
life cycle of a cell which is marked by cell division which is
separated into four phases: G1, S, G2, and M. DNA replication is
confined to the S(synthesis) phase, and chromosomal separation in the
M (mitotic) phase.
Chimeric
clone
A
cloning artifact created by a foreign gene being inserted into a
vector in an incorrect orientation resulting in theexpression of a
protein consisting of a fusion of two different gene
products.
Chromat
Data
file output from most popular DNA sequencers. Chromat files consist
of the fluorescent traces generated by the sequencer for each of the
four chemical bases, A, C, G, and T, together with the sequence and
measures of the error in the traces at each sequence
position.
Chromatin
The
chromosome as it appears in its condensed state, composed of DNA and
associated proteins (mainly histones).
Chromosome
The
structure in the cell nucleus that contains all of the cellular DNA
together with a number of proteins that compact and package the
DNA.
Clinical
trials
Research
studies that involve patients. Biotechnology companies typically use
clinical trials to assess the efficacy and safety of new therapies
and to answer scientific questions. Typically, there are 3 phases
during a clinical trial. Phase I is designed to evaluate the safety
of the product in humans; phase II analyses the effects of dose
escalation, and phase III definitively evaluates the clinical
efficacy of the product.
Clone
A
population of genetically identical cells or DNA
molecules.
Cloning
The
formation of clones or exact genetic replicas.
Cluster
The
grouping of similar objects in a multidimensional space.
Clustering is used for constructing new features which are
abstractions of the existing features of those objects. The quality
of the clustering depends crucially on the distance metric in the
space. In bioinformatics, clustering is performed on sequences,
high-throughput expression and other experimental data. Clusters of
partial or complete gene sequences can be used to identify the
complete (contiguous) sequence and to better identify its function.
Clustering expression data enables the researcher to discern patterns
of co-regulation in groups of genes.
Coding
regions (CDS)
The
portion of a genomic sequence bounded by start and stop codons that
identifies the sequence of the protein being coded for by a
particular gene.
Codon
A
sequence of three adjacent nucleotides that designates a specific
amino acid or start/stop site for transcription.
Combinatorial
chemistry
The
use of chemical methods to generate all possible combinations of
chemicals starting with a subset of compounds. The building blocks
may be peptides, nucleic acids or small molecules. The libraries of
compounds formed by this methodology are used to probe for new
pharmaceutical reagents (see high-throughput screening).
Complementary
determining region (CDR)
The
hypervariable regions of an antibody molecule, consisting of three
loops from the heavy chain and three from the light chain, that
together form the antigen-binding site.
Complexity
(of gene sequence)
The
term "low complexity sequence" may be thought of as synonymous with
regions of locally biased amino acid composition. In these regions,
the sequence composition deviates from the random model thatunderlies
the calculation of the statistical significance (P-value) of an
alignment. Such alignments among low complexity sequences are
statistically but not biologically significant, i.e., one cannot
infer homology (common ancestry) or functional similarity.
Configuration
(in
software) The complete ordering and description of all parts of a
software or database system. Configuration management is the
use of software to identify, inventory and maintain the component
modules that together comprise one or more systems or
products.
Conformation
The
precise three-dimensional arrangement of atoms and bonds in a
molecule describing its geometry and hence its molecular
function.
Consensus
sequence
A
single sequence delineated from an alignment of multiple
constituent sequences that represents a "best fit" for all those
sequences. A "voting" or other selection procedure is used to
determine which residue (nucleotide or amino acid) is placed at a
given position in the event that not all of the constituent sequences
have the identical residue at that position.
Constitutive
synthesis (expression)
Synthesis
of mRNA and protein at an unchanging or constant rate regardless of a
cellís requirements (see housekeeping genes).
Contig
A
length of contiguous sequence assembled from partial, overlapping
sequences, generated from a "shotgun" sequencing project.
Contigs are typically created computationally, by comparing the
overlapping ends of several sequencing reads generated by restriction
enzyme digestion of a segment of genomic DNA. The creation of
contigs in the presence of sequencing errors, ambiguities and the
presence of repeats is one of the most computationally challenging
aspects of the role of Bioinformatics in genome analysis.
Convergence
The
end-point of any algorithm that uses iteration or recursion to guide
a series of data processing steps. An algorithm is usually said to
have reached convergence when the difference between the computed and
observed steps falls below a pre-defined threshold.
Cosmids
DNA
vectors that allow the insertion of long fragments of DNA (up to 50
kbases).
Crystal
structure
Term
used to describe the high resolution molecular structure derived by
x- ray crytallographic analysis of protein or other biomolecular
crystals.
Cytoplasm
The
medium of the cell between the nucleus and the cell
membrane.
Cytosine
A
pyrimidine base found in DNA and RNA.
Data
Cleaning
A
process whereby automated or semi-automated algorithms are used to
process experimental data, including noise, experimental errors and
other artifacts, in order to generate and store high-quality data for
use in subsequent analysis. Data cleaning is typically required in
high-throughput sequencing where compression or other experimental
artifacts limit the amount of sequence data generated from each
sequencing run or "read."
Data
Mining
The
ability to query very large databases in order to satisfy a
hypothesis ("top-down" data mining); or to interrogate a database in
order to generate new hypotheses based on rigorous statistical
correlations ("bottom-up" data mining).
Data
Processing
Data
processing is defined as the systematic performance of operations
upon data such as handling, merging, sorting, and computing. The
semantic content of the original data should not be changed, but the
semantic content of the processed data may be changed.
Data
Warehouses
Vast
arrays of heterogeneous (biological) data, stored within a single
logical data repository, that are accessible to different querying
and manipulation methods.
Database
Any
file system by which data gets stored following a logical
process. (see also relational database)
Deconvolution
Mathematical
procedure to separate out the overlapping effects of molecules such
as mixtures of compounds in a high-throughput screen, or mixtures of
cDNAs in a high density array.
Deletion
A
chromosomal alteration in which a portion of the chromosome or the
underlying DNA is lost.
Deletion
mapping
Process
in which different deletions in a region of DNA are created and used
to map the functionally critical areas of that DNA. e.g the minimal
region of DNA required for a test promoter can be ascertained by
systematic deletions in the region of interest.
Dendrogram
A
graphical procedure for representing the output of a hierarchical
clustering method. A dendrogram is strictly defined as a binary
tree with a distinguished root, that has all the data items at its
leaves. Conventionally, all the leaves are shown at the same
level of the drawing. The ordering of the leaves is arbitrary,
as is their horizontal position. The heights of the internal nodes
may be arbitrary, or may be related to the metric information used to
form the clustering.
Dimer
A
composite molecule formed by the binding of two molecules (see homo
and heterodimers).
Disulphide
bond
Covalent
link formed between the sulphur atoms of two different cysteine
residues in a protein. Important in maintaining the folded structure
of a protein, and also for linking different proteins in a
complex.
DNA
(deoxyribonucleic acid)
The
chemical that forms the basis of the genetic material in virtually
all organisms. DNA is composed of the four nitrogenous bases Adenine,
Cytosine, Guanine, and Thymine, which are covalently bonded to a
backbone of deoxyribose-phosphate to form a DNA strand. Two
complementary strands (where all Gs pair with Cs and As with Ts) form
a double helical structure which is held together by hydrogen bonding
between the cognate bases.
DNA
fingerprinting
A
technique for identifying human individuals based on a restriction
enzyme digest of tandemly repeated DNA sequences that are scattered
throughout the human genome, but are unique to each
individual.
DNA
microarrays
The
deposition of oligonucleotides or cDNAs onto an inert substrate such
as glass or silicon. Thousands of molecules may be organized
spatially into a high-density matrix. These DNA chips may be probed
to allow expression monitoring of many thousands of genes
simultaneously. Uses include study of polymorphisms in genes, de novo
sequencing or molecular diagnosis of disease.
DNA
polymerase
An
enzyme that catalyzes the synthesis of DNA from a DNA template given
the deoxyribonucleotide precursors.
DNA
probes
Short
single stranded DNA molecules of specific base sequence, labeled
either radioactively or immunologically, that are used to detect and
identify the complementary base sequence in a gene or genome by
hybridizing specifically to that gene or sequence.
DNA
sequencing
The
technique in which the specific sequence of bases forming a
particular DNA region is deciphered.
DNase
(Deoxyribonuclease)
One
of a series of enzymes that can digest DNA.
Domain
(protein)
A
region of special biological interest within a single protein
sequence. However, a domain may also be defined as a region within
the three-dimensional structure of a protein that may encompass
regions of several distinct protein sequences that accomplishes a
specific function. A domain class is a group of domains that share a
common set of well-defined properties or characteristics.
Drug
An
agent that affects a biological process. Specifically, a molecule
whose molecular structure can be correlated with its pharmacological
activity.
Drug
discovery cycle
The
cycle of events required to develop a new drug. Typically this
involves research, preclinical testing and clinical development, and
can take from 5 to 12 years.
Electronic
Northerns
The
use of an electronic database of cDNA sequences (or probes derived
from them) in order to measure the relative levels of mRNAs expressed
in different cells or tissues. An example of the use of an electronic
Northern might be to identify the differences in the genes expressed
in prostate cancer and those in benign prostate hyperplasia, by
subtracting the database of one from the other and seeing which cDNAs
remain.
Electrophoresis
The
use of an external electric field to separate large biomolecules on
the basis of their charge by running them through acrylamide
or agarose gels.
Enhancers
DNA
sequences that can greatly increase the transcription rates of genes
even though they may be far upstream or downstream from the promoter
they stimulate.
Enzyme
A
class of proteins that are capable of catalyzing chemical reactions
(the making or breaking of chemical bonds). They do so by orienting
their substrates into a suitable geometry in a particular location
(the active site) where electrophilic or nucleophilic amino acid
residues can participate in the reaction. Enzymes are protein
catalyst that speeds up chemical reactions that would otherwise be
prohibitively slow under physiological conditions.
Epigenomics
The
study of complex expression networks or linkages both spatially
(within the body) and temporally (at different times in
development).
Equilibrium
constant
Value
that describes the equilibrium state of the reversible reaction
between two molecular species.
Eukaryote
A
cell or organism with a distinct membrane-bound nucleus as well as
specialized membrane-based organelles (see also
prokaryote).
Exon
The
region of DNA within a gene that codes for a polypeptide chain or
domain. Typically a mature protein is composed of several domains
coded by different exons within a single gene.
Expressed
Sequence Tags (ESTs)
A
small sequence from an expressed gene that can be amplified by PCR.
ESTs act as physical markers for cloning and full length sequencing
of the cDNAs of expressed genes. Typically identified by purifying
mRNAs, converting to cDNAs, and then sequencing a portion of the
cDNAs.
Expression
(gene or protein)
A
measure of the presence, amount, and time-course of one or more gene
products in a particular cell or tissue. Expression studies are
typically performed at the RNA (mRNA) or protein level in order to
determine the number, type, and level of genes that may be
up-regulated or down-regulated during a cellular process, in response
to an external stimulus, or in sickness or disease. Gene chips
and proteomics now allow the study of expression profiles of sets of
genes or even entire genomes.
Expression
profile
The
level and duration of expression of one or more genes, selected from
a particular cell or tissue type, generally obtained by a variety of
high-throughput methods, such as sample sequencing, serial analysis,
or microarray-based detection.
Expression
vector
A
cloning vector that is engineered to allow the expression of protein
from a cDNA. The expression vector provides an appropriate promoter
and restriction sites that allow insertion of cDNA.
Fingerprint
A
fingerprint is a set of motifs used to predict the occurrence of
similar motifs, in either an individual sequence or in a database.
Fingerprints are refined by iterative scanning of a composite protein
sequence database. A composite or multiple-motif fingerprint
contains a number of aligned motifs taken from different parts of a
multiple alignment. True family members are then easy to
identify by virtue of possessing all elements of the fingerprint,
while subfamily members may be identified by possessing only part of
it.
Frameshift
A
deletion, substitution, or duplication of one or more bases that
causes the reading-frame of a structural gene to shift from the
normal series of triplets.
Functional
genomics
The
use of genomic information to delineate protein structure, function,
pathways and networks. Function may be determined by "knocking out"
or "knocking in" expressed genes in model organisms such as worm,
fruitfly, yeast or mouse.
Fusion
protein
The
protein resulting from the genetic joining and expression of 2
different genes (see chimeric)
Gaps
(affine gaps)
A gap
is defined as any maximal, consecutive run of spaces in a single
string of a given alignment. Gaps help create alignments that better
conform to underlying biological models and more closely fit patterns
that one expects to find in meaningful alignment. The idea is to take
in account the number of continuous gaps and not only the number of
spaces when calculating an alignment. Affine gaps contain a component
for gap insertion and a component for gap extension, where the
extension penalty is usually much lower than the insertion penalty.
This mimics biological reality as multiple gaps would imply multiple
mutations, but a single mutation can lead to a long gap quite
easily.
Gap
penalties
The
penalty applied to a similarity score for the introduction of an
insertion or deletion gap, the extension of a gap, or both. Gap
penalties are usually subtracted from a cumulative score being
determined for the comparison of two or more sequences via an
optimization algorithm that attempts to maximize that
score.
Gel
electrophoresis
A
technique by which molecules are separated by size or charge by
passing them through a gel under the influence of an external
electric field.
Gene
Index
A
listing of the number, type, label and sequence of all the genes
identified within the genome of a given organism. Gene indices are
usually created by assembling overlapping EST sequences into
clusters, and then determining if each cluster corresponds to a
unique gene. Methods by which a cluster can be identified as
representing a unique gene include identification of long open
reading frames (ORFs), comparison to genomic sequence, and detection
of SNPs or other features in the cluster that are known to exist in
the gene.
GenBank
Data
bank of genetic sequences operated by a division of the National
Institutes of Health.
Gene
Classically,
a unit of inheritance. In practice, a gene is a segment of DNA on a
chromosome that encodes a protein and all the regulatory sequences
(promoter) required to control expression of that protein.
Gene
chips (also Gene arrays)
The
covalent attachment of oligonucleotides or cDNA directly onto a small
glass or silicon chip in organized arrays. Over 50,000 different DNA
fragments can be presented on a single chip providing a high
throughput parallel method of probing gene expression, genotype or
gene function.
Gene
expression
The
conversion of information from gene to protein via transcription and
translation.
Gene
families
Subsets
of genes containing homologous sequences which usually correlate with
a common function.
Gene
library
A
collection of cloned DNA fragments created by restriction
endonuclease digestion that represent part or all of an
organismís genome.
Gene
product
The
product, either RNA or protein, that results from expression of a
gene. The amount of gene product reflects the activity of the
gene.
Gene
therapy
The
use of genetic material for therapeutic purposes. The therapeutic
gene is typically delivered using recombinant virus or liposome based
delivery systems.
Genetic
code
The
mapping of all possible codons into the 20 amino acids including the
start and stop codons.
Genetic
engineering (Recombinant DNA technology)
The
procedures used to isolate, splice and manipulate DNA outside the
cell. Genetic Engineering allows a recombinantly engineered DNA
segment to be introduced into a foreign cell or organism, and be able
to replicate and function normally.
Genetic
marker
Any
gene that can be readily recognized by its phenotypic effect, and
which can be used as a marker for a cell, chromosome, or individual
carrying that gene. Also, any detectable polymorphism used to
identify a specific gene.
Genome
The
complete genetic content of an organism.
Genomic
DNA (sequence)
DNA
sequence typically obtained from mammalian or other higher-order
species, which includes both intron and exon sequence (coding
sequence), as well as non-coding regulatory sequences such as
promoter, and enhancer sequences.
Genomics
The
analysis of the entire genome of a chosen organism.
Genotype
Strictly,
all of the genes possessed by an individual. In practice, the
particular alleles present in a specific genetic locus.
Glycosylation
The
addition of carbohydrate groups (sugars) e.g. to polypeptide
chains
Guanine
(G)
One
of the nitrogenous purine bases found in DNA and RNA
Hairpin
A
double-helical region in a single DNA or RNA strand formed by the
hydrogen-bonding between adjacent inverse complementary sequences to
form a hairpin shaped structure.
Haploid
A
cell or organism containing only one set of chromsomes without the
homologous pairs. (cf. diploid)
Heterodimer
Protein
composed of 2 different chains or subunits.
Heteroduplex
Hybrid
structure formed by the annealing of two DNA strands (or an RNA and
DNA) that have sufficient complementarity in their sequence to allow
hydrogen bonding.
Hidden
Markov model (HMM)
A
joint statistical model for an ordered sequence of variables.
The result of stochastically perturbing the variables in a Markov
chain (the original variables are thus "hidden"), where the Markov
chain has discrete variables which select the "state" of the HMM at
each step. The perturbed values can be continuous and are the
"outputs" of the HMM. A Hidden Markov Model is equivalently a coupled
mixture model where the joint distribution over states is a Markov
chain. Hidden Markov models are valuable in bioinformatics because
they allow a search or alignment algorithm to be trained using
unaligned or unweighted input sequences; and because they allow
position-dependent scoring parameters such as gap penalties, thus
more accurately modeling the consequences of evolutionary events on
sequence families.
High-throughput
screening
The
method by which very large numbers of compounds are screened against
a putative drug target in either cell-free or whole-cell assays.
Typically, these screenings are carried out in 96 well plates using
automated, robotic station based technologies or in higher- density
array ("chip") formats.
HLA
complex
Another
name for the MHC in humans; refers to the "Human Leukocyte Antigen"
complex located on chromosome 6.
Homeobox
A
highly conserved region in a homeotic gene composed of 180 bases (60
amino acids) that specifies a protein domain (the homeodomain) that
serves as a master genetic regulatory element in cell differentiation
during development in species as diverse as worms, fruitflies, and
humans.
Homeodomain
A 60
amino-acid protein domain coded for by the homeobox region of a
homeotic gene.
Homeotic
gene
A
gene that controls the activity of other genes involved in the
development of a body plan. Homeotic genes have been found in
organisms ranging from plants to humans.
Homology
(strict)
Two or more biological species, systems or molecules that share a
common evolutionary ancestor. (general) Two or more gene or protein
sequences that share a significant degree of similarity, typically
measured by the amount of identity (in the case of DNA), or
conservative replacements (in the case of protein), that they
register along their lengths. Sequence "homology" searches are
typically performed with a query DNA or protein sequence to identify
known genes or gene products that share significant similarity and
hence might inform on the ancestry, heritage and possible function of
the query gene.
Housekeeping
genes
Genes
that are always expressed (ie. they are said to be constitutively
expressed) due to their constant requirement by the cell.
Human
Anti-Murine Antibody Response (HAMA)
An
immune response generated in humans to antibodies raised in murine
(e.g. mouse or rat) cells.
Hybridization
The
interaction of complementary nucleic acid strands. This can occur
between two DNA strands or between DNA and RNA strands, and is the
basis of many techniques such as Southern and northern
blots.
Hydrogen
bond
A
weak chemical interaction between an electronegative atom (e.g.
nitrogen or oxygen) and a hydrogen atom that is covalently attached
to another atom. This bond maintains the two-helices of DNA together
and is also the primary interaction between water
molecules.
Hydrophilicity
(lit.
water-loving) The degree to which a molecule is soluble in water.
Hydrophilicity depends to a large degree on the charge and
polarizability of the molecule and its ability to form transient
hydrogen-bonds with (polar) water molecules.
Hydrophobicity
(lit.
water-hating) The degree to which a molecule is insoluble in water,
and hence is soluble in lipids. If a molecule lacking polar groups is
placed in water, it will be entropically driven to finding a
hyrdophobic environment (such as the interior of a protein or a
membrane).
Idiotype
Antibody
variants localized to the variable portion of an immunoglobulin that
are recognised by their antigenic determinants. The determinants are
composed from the antigen-combining site or CDRs. Every unique
antigenic determinant has a specific antibody with its own unique
idiotype.
Immunoglobulin
A
member of the globulin protein family consisting of two light and two
heavy chains linked by disulfide bonds. All antibodies are
immunoglobulins.
in
silico (biology)
(Lit.
computer mediated). The use of computers to simulate, process, or
analyse a biological experiment.
in
situ hybridization
A
variation of the DNA/RNA hybridization procedure in which the
denatured DNA is in place in the cell and is then challenged with RNA
or DNA extracted from another source. (See also fluorescence in situ
hybridization).
Integration
The
physical insertion of DNA into the host cell genome. The process is
used by retroviruses where a specific enzyme catalyses the process or
can occur at random sites with other DNA (eg.
transposons).
Intracellular
signalling
The
communication of a molecular message from the surface of the cell to
the nucleus via the participation of a series of molecules, including
receptors, enzymes, proteins, and small-molecules. The end result of
the signalling process is the up- or down-regulation of a particular
series of genes that may be involved in cell growth, division or
differentiation.
Introns
Nucleotide
sequences found in the structural genes of eukaryotes that are
non-coding and interrupt the sequences containing information that
codes for polypeptide chains. Intron sequences are spliced out of
their RNA transcripts before maturation and protein synthesis. (cf.
Exons)
Isoschizomers
Two
different restriction enzymes which recognize and cut DNA at the same
recognition site. e.g Sma I and Xma I both recognize and cut the
sequence CCCGGG.
Isozymes
Two
or more enzymes capable of catalyzing the same reaction but varying
in their specificity due to differences in their structures and hence
their efficiencies under different environmental
conditions.
Iteration
A
series of steps in an algorithm whereby the processing of data is
performed repetitively until the result exceeds a particular
threshold. Iteration is often used in multiple sequence alignments
whereby each set of pairwise alignments are compared with every
other, starting with the most similar pairs and progressing to the
least similar, until there are no longer any sequence-pairs remaining
to be aligned.
Junk
DNA
Term
used to describe the excess DNA that is present in the genome beyond
that required to encode proteins. A misleading term since these
regions are likely to be involved in gene regulation, and other as
yet unidentified functions.
Karyotype
The
constitution (typically number and size) of chromosomes in a cell or
individual.
Knockout
mice (gene targeting)
Mice
which have been engineered to lack a chosen gene. The gene is
inactivated in so called embryonic stem cells using the technique of
homologous recombination. These cells are then introduced into a
early stage embryo (blastocyst) and this is then transplanted into a
recipient mouse. The subsequent progeny lack the targeted gene in
some cells. This technique is used to determine the function of the
chosen gene.
"Lab
on a chip"
Term
describing microdevices that allow rapid, microanalytical analysis of
DNA or protein in a single, fully integrated system. Typically, these
devices are miniature surfaces, made of silicon, glass or plastic,
which carry the necessary microdevices (pumps, valves, microfluidic
controllers, and detectors) that allow sample separation and
analysis. These devices are used in drug discovery, genetic testing
and separation science.
Lead
compound
A
candidate compound identified as the best "hit" (tight binder) after
screening of a combinatorial (or other) compound library, that is
then taken into further rounds of screening to determine its
suitability as a drug.
Lead
optimization
The
process of converting a putative lead compound ("hit") into a
therapeutic drug with maximal activity and minimal side affects,
typically using a combination of computer-based drug design,
medicinal chemistry and pharmacology.
Leucine
zipper
Protein
motif which binds DNA in which 4-5 Leucines are found at 7 amino acid
intervals. This motif is present typically in transcription factors
and other proteins that bind DNA.
Lexicon
In
Bioinformatics, a lexicon refers to a pre-defined list of terms that
together completely define the contents of a particular
database.
(strict.)
The component in the grammar which is in bare form a list of words or
lexical entries.
Library
A
large collection of compounds, peptides, cDNAs or genes which may be
screened in order to isolate cognate molecules.
Ligand
Any
small molecule that binds to a protein or receptor; the cognate
partner of many cellular proteins, enzymes, and receptors.
Linkage
The
association of genes (or genetic loci) on the same chromosome. Genes
that are linked together tend to be transmitted together.
Linkage
map
A
genetic map of a chromosome or genome delineated by mapping the
positions of genes to their chromosomes by their linkage to readily
identifiable genetic loci.
Locus
The
specific position occupied by a gene on a chromosome. At a given
locus, any one of the variant forms of a gene may be present. The
variants are said to be alleles of that gene.
Map
unit
A
measure of genetic distance between two linked genes that corresponds
to a recombination frequency of 1%.
Markov
chain
Any
multivariate probability density whose independence diagram is a
chain.The variables are ordered, and each variable "depends" only on
its neighbors in the sense of being conditionally independent of the
others. Markov chains are an integral component of hidden
Markov models.
Meiosis
A
process within the cell nucleus that results in the reduction of the
chromosome number from diploid (two copies of each chromosome) to
haploid (a single copy) through two reductive divisions in germ
cells.
Melting
(of DNA)
The
denaturation of double-stranded DNA into two single strands by the
application of heat. (Denaturation breaks the hydrogen bonds holding
the double-stranded DNA together).
Messenger
RNA (mRNA)
The
complementary RNA copy of DNA formed from a single-stranded DNA
template during transcription that migrates from the nucleus to the
cytoplasm where it is processed into a sequence carrying the
information to code for a polypeptide domain.
Methylation
The
addition of -CH3 (methyl) groups to a target site. Typically such
addition occurs on to the cytosine bases of DNA. (see maternal
imprinting).
Microarray
A 2D
array, typically on a glass, filter, or silicon wafer, upon which
genes or gene fragments are deposited or synthesized in a
predetermined spatial order allowing them to be made available as
probes in a high-throughput, parallel manner.
Microfluidics
The
miniaturization of chemical reactions or pharmacalogical assays into
microscopic tubes or vessels in order to greatly increase their
throughput, by placing many of them side-by-side in an
array.
Mimetics
Compounds
that mimic the function of other molecules via their high degree of
structural (conformational) similarity, and hence physio-chemical
properties.
Missense
mutation
A
point mutation in which one codon (triplet of bases) is changed into
another designating a different amino acid.
Mitosis
The
nuclear division that results in the replication of the genetic
material and its redistribution into each of the daughter cells
during cell division.
Modeling
In
bioinformatics, modeling usually refers to molecular modeling, a
process whereby the three-dimensional architecture of biological
molecules is interpreted (or predicted), visually represented, and
manipulated in order to determine their molecular properties.
(general) A series of mathematical equations or procedures which
simulate a real-life process, given a set of assumptions, boundary
parameters, and initial conditions.
Monomer
A
single unit of any biological molecule or macromolecule, such as an
amino acid, nucleic acid, polypeptide domain, or protein.
Monovalent
Having
one binding site; strictly, an atom with only one free electron
available for binding in its highest energy shell.
Motif
A
conserved element of a protein sequence alignment that usually
correlates with a particular function. Motifs are generated from a
local multiple protein sequence alignment corresponding to a region
whose function or structure is known. It is sufficient that it is
conserved, and is hence likely to be predictive of any subsequent
occurrence of such a structural/functional region in any other novel
protein sequence.
Multigene
family
A set
of genes derived by duplication of an ancestral gene, followed by
independent mutational events resulting in a series of independent
genes either clustered together on a chromosome or dispersed
throughout the genome.
Multiple
(sequence) alignment
A
Multiple Alignment of k sequences is a rectangular array,
consisting of characters taken from the alphabet A, that
satisfies the following conditions: There are exactly k rows;
ignoring the gap character, row number i is exactly the
sequence sI; and each column contains at least one
character different from "-". In practice multiple sequence
alignments include a cost/weight function, that defines the penalty
for the insertion of gaps (the "-" character) and weights identities
and conservative substitutions accordingly. Multiple alignment
algorithms attempt to create the optimal alignment defined as the one
with the lowest cost/weight score.
Multiplex
sequencing
Approach
to high-throughput sequencing that uses several pooled DNA samples
run through gels simultaneously and then separated and
analyzed.
Mutagen
Any
agent that can cause an increase in the rate of mutations in an
organism.
Mutation
An
inheritable alteration to the genome that includes genetic (point or
single base) changes, or larger scale alterations such as chromosomal
deletions or rearrangements.
Naked
DNA
Pure,
isolated DNA devoid of any proteins that may bind to it.
NCEs
(New Chemical Entity)
Compounds
identified as potential drugs that are sent from research and
development into clinical trials to determine their
suitability.
Nested
PCR
The
second round amplification of an already PCR-amplified sequence using
a new pair of primers which are internal to the original primers.
Typically done when a single PCR reaction generates insufficient
amounts of product.
Neural
net
A
neural net is an interconnected assembly of simple processing
elements, units or nodes, whose functionality is loosely based on the
animal brain. The processing ability of the network is stored in the
inter-unit connection strengths, or weights, obtained by a process of
adaptation to, or learning from, a set of training patterns. Neural
nets are used in bioinformatics to map data and make predictions,
such as taking a multiple alignment of a protein family as a training
set in order to identify novel members of the family from their
sequence data alone.
Nonsense
mutation
A
point mutation in which a codon specific for an amino-acid is
converted into a nonsense codon.
Northern
blotting
A
technique to identify RNA molecules by hybridization that is
analogous to Southern blotting (see Southern blotting).
Nuclease
Any
enzyme that can cleave the phosphodiester bonds of nucleic acid
backbones.
Nucleoside
A
five-carbon sugar covalently attached to a nitrogen base.
Nucleotide
A
nucleic acid unit composed of a five carbon sugar joined to a
phosphate group and a nitrogen base.
Object-Relational
Database
Object
databases combine the elements of object orientation and
object-oriented programming languages with database capabilities.
They provide more than persistent storage of programming language
objects. Object databases extend the functionality of object
programming languages (e.g., C++, Smalltalk, or Java) to provide
full-featured database programming capability. The result is a high
level of congruence between the data model for the application and
the data model of the database. Object-relational databases are
used in Bioinformatics to map molecular biological objects (such as
sequences, structures, maps and pathways) to their underlying
representations (typically within the rows and columns of relational
database tables.) This enables the user to deal with the biological
objects in a more intuitive manner, as they would in the laboratory,
without having to worry about the underlying data model of their
representation.
Oligonucleotide
A
short molecule consisting of several linked nucleotides (typically
between 10 and 60) covalently attached by phosphodiester
bonds.
Open
reading frame (ORF)
Any
stretch of DNA that potentially encodes a protein. Open reading
frames start with a start codon, and end with a termination codon. No
termination codons may be present internally. The identification of
an ORF is the first indication that a segment of DNA may be part of a
functional gene.
Operator
A
segment of DNA that interacts with the products of regulatory genes
and facilitates the transcription of one or more structural
genes.
Operon
A
unit of transcription consisting of one or more structural genes, an
operator, and a promoter.
Ortholog
Orthologs
are genes in different species that evolved from a common ancestral
gene by speciation. Normally, orthologs retain the same function in
the course of evolution. Identification of orthologs is critical for
reliable prediction of gene function in newly sequenced genomes. (See
also Paralogs.)
Overlapping
clones
Collection
of cloned sequences made by generating randomly overlapping DNA
fragments with infrequently cutting restriction enzymes.
Palindrome
A
region of DNA with a symmetrical arrangement of bases occuring about
a single point such that the base sequences on either side of that
point are identical (if the strands are both read in the same
direction) e.g 5í GAATTC 3í whose complementary
sequence is 3í CTTAAG 5í.
Pattern
Molecular
biological patterns usually occur at the level of the characters
making up the gene or protein sequence. A pattern language must be
defined in order to apply different criteria to different positions
of a sequence. In order to have position-specific comparison done by
a computer, a pattern-matching algorithm must allow alternative
residues at a given position, repetitions of a residue, exclusion of
alternative residues, weighting, and ideally, combinatorial
representation.
Pathways
Bioinformatics
strives to define representations of key biological datatypes,
algorithms and inference procedures, including sequences, structures,
biological pathways and reactions. Representing and computing with
biological pathways requires ontologies for representing pathway
knowledge; User interfaces to these databases; Physico-chemical
properties of enzymes and their substrates in pathways; And pathway
analysis of whole genomes including identifying common patterns
across species and species differences.
Paralog
Paralogs
are genes related by duplication within a genome. Orthologs retain
the same function in the course of evolution, whereas paralogs evolve
new functions, even if these are related to the original
one.
Parameters
Parameters
are user-selectable values, typically experimentally determined, that
govern the boundaries of an algorithm or program. For instance,
selection of the appropriate input parameters governs the success of
a search algorithm. Some of the most common search parameters in
bioinformatics tools include the stringency of an alignment search
tool, and the weights (penalties) provided for mismatches and
gaps.
Peptide
A
short stretch of amino acids each covalently coupled by a peptide
(amide) bond.
Peptide
bond (amide bond)
A
covalent bond formed between two amino acids when the amino group of
one is linked to the carboxy group of another (resulting in the
elimination of one water molecule).
Phage
(Bacteriophage)
A
virus that infects bacterial cells and serves as a useful vector for
introducing genes into bacteria for a number of purposes.
Phage
display
A
technique in which phage are engineered to fuse a foreign peptide or
protein with their capsid (surface) proteins and hence display it on
their cell surfaces. The immobilized phage may then be used as a
screen to see what ligands bind to the expressed fusion protein
exhibited (displayed) on the phage surface.
Pharmacogenomics
The
use of (DNA-based) genotyping in order to target pharmaceutical
agents to specific patient populations. Genetic differences are known
to affect responses to many types of drug therapy, and
pharmacogenomics analysis serves to customize the use of
pharmaceuticals for specific subgroups of patients.The rationale for
this approach is that observed gene expression differences may
correlate with, and explain, the differences in side effects and
efficacy to drugs in humans.
Pharmacophore
The
three dimensional spatial arrangment of atoms, substituents,
functional groups, or chemical features that together are sufficient
to describe the pharmacologically active components of a drug
molecule or molecule series.
Phenotype
Any
observable feature of an organism that is the result of one or more
genes.
Phylum
The
segmentation of the animal kingdom into about 30 major groups
collectively known as phyla. The members of each phylum share the
same basic structure and organization. For instance, fish, birds, and
human beings belong to one phylum - the Chordata - because all have
spinal cords.
Physical
map
A
physical map consists of a linearly ordered set of DNA fragments
encompassing the genome or region of interest. Physical maps are of
two types, macro-restriction maps and ordered clone maps. The former
consists of an ordered set of large DNA fragments generated by using
restriction enzymes whose recognition sequences are infrequently
represented in the genome. An ordered clone map consists of an
overlapping collection of cloned DNA fragments. The DNA may be cloned
into any one of the available vector systems--YACs, cosmids, phage,
or even plasmids. Major advantages of ordered clone
maps are
that they are of high resolution and directly provide the clones for
further study.
Plasmid
Any
replicating DNA element that can exist in the cell independently of
the chromosomes. Synthetic plasmids are used for DNA cloning. Most
commonly found in bacterial cells.
Pleitropy
The
multiple effects on an organismís phenotype due to a single
gene or allele e.g the cytokines which can bind to multiple cellular
receptors and effect growth and multiple immune pathways.
Point
mutation
A
mutation in which a single nucleotide in a DNA sequence is
substituted by another nucleotide.
Poly(A)
tail
The
stretch of Adenine (A) residues at the 3í end of eukaryotic
mRNA that is added to the pre-mRNA as it is processed, before its
transport from the nucleus to the cytoplasm and subsequent
translation at the ribosome.
Polyadenylation
site
A
site on the 3í-end of messenger RNA (mRNA) that signals the
addition of a series of Adenines during the RNA processing step and
before the mRNA migrates to the cytoplasm. These so-called
poly(A) "tails" increase mRNA stability andallow one to isolate mRNA
from cells by PCR-amplification using poly(T) primers.
Polygenic
inheritance
Inheritance
involving alleles at many genetic loci.
Polymerase
chain reaction (PCR )
Technique
used to amplify or generate large amounts of replica DNA of a segment
of any DNA whose "flanking" sequences are known. Oligonucleotide
primers which bind these flanking sequences are used by an enzyme
(Taq polymerase) to copy the sequence in between the primers. Cycles
of heat to break apart the DNA strands, cooling to allow the primers
to bind, and heating again to allow the enzyme to copy the
intervening sequence lead to a doubling of DNA at each cycle. The
reactions are typically carried out on a regulated heating block and
consist of 30-35 cycles of repeated amplification of all the DNA
present. Single molecules of "target" DNA can be amplified to
microgram amounts of DNA. The target DNA can be of any
origin.
Polymorphism
(lit.
many forms) The existence of a gene in a population in at least two
different forms at a frequency far higher than that attributable to
recurrent mutation alone. Variations in a population may be measured
by determining the rate of mutation in polymorphic genes (see
SNPs).
Polypeptide
A
single chain of covalently attached amino acids joined by peptide
bonds. Polypeptide chains usually fold into a compact, stable form (a
domain) that is part (or all) of the final protein.
Positional
cloning
Method
used to define the location of a gene on a chromosome and use this
information to identify and clone the gene. The location of the gene
is determined by linkage analysis of DNA from a large family
containing afflicted and normal members to identify linkages between
the transmission of the disease gene and observable genetic markers.
This information is then used to screen (by chromosomal jumping and
walking) the location for putative genes. The disease gene must be
compared between the afflicted and normal family members and be shown
to be different in the two groups. The full sequencing of the gene
will then provide information regarding the characteristics and
function of the gene product, and a potential explanation for the
cause of the disease.
Post-transcriptional
modification
Alterations
made to pre-mRNA before it leaves the nucleus and becomes mature
mRNA.
Post-translational
modification
Alterations
made to a protein after its synthesis at the ribosome. These
modifications, such as the addition of carbohydrate or fatty acid
chains, may be critical to the function of the protein.
Primary
sequence (protein)
The
linear sequence of a polypeptide or protein.
Primary
structure (protein)
see
primary sequence.
Primer
A
short oligonucleotide that provides a free 3í hydroxyl for DNA
or RNA synthesis by the appropriate polymerase (DNA polymerase or RNA
polymerase).
Probe
Any
biochemical that is labelled or tagged in some way so that it can be
used to identify or isolate a gene, RNA, or protein.
Profile
Sequence
profiles are usually derived from multiple alignments of sequences
with a known relationship, and consist of tables of position-specific
scores and gap-penalties. Each position in the profile contains
scores for all of the possible amino acids, as well as one penalty
score for opening and one for continuing a gap at the specified
position. Attempts have been made to further improve the sensitivity
of the profile by refining the procedures to construct a profile
starting from a given multiple alignment. Other representations for
sequence domains or motifs do not necessarily require the presence of
a correct and complete multiple alignment, such as hidden Markov
models.
Prokaryote
An
organism or cell that lacks a membrane-bounded nucleus. Bacteria and
blue-green algae are the only surviving prokaryotes (cf.
Eukaryote).
Promoter
(site)
A
promoter site is defined by its recognition by eukaryotic RNA
polymerase II; its activity in a higher eukaryote; by experimentally
evidence, or homology and sufficient similarity to an experimentally
defined promoter; and by observed biological function.
Protein
families
Sets
of proteins that share a common evolutionary origin reflected by
their relatedness in function which is usually reflected by
similarities in sequence, or in primary, secondary or tertiary
structure. Subsets of proteins with related structure and
function.
Proteome
The
entire protein complement of a given organism.
Proteomics
The
study of the proteome. Typically, the cataloging of all the expressed
proteins in a particular cell or tissue type, obtained by identifying
the proteins from cell extracts using a combination of 2D gel
electrophoresis and mass spectrometry. The large scale analysis of
the protein composition and function. (cf genomics)
Purine
A
nitrogen-containing compound with a double-ring structure. The parent
compound of Adenine and Guanine.
Pyrimidine
A
nitrogen-containing compound with a single six-membered ring
structure. The parent compound of Thymidine and Cytosine.
Query
(sequence)
A
DNA, RNA of protein sequence used to search a sequence database in
order to identify close or remote family members (homologs) of known
function, or sequences with similar active sites or regions
(analogs), from whom the function of the query may be
deduced.
Rational
drug design (Structure based drug design)
The
development of drugs based on the 3-dimensional molecular structure
of a particular target.
Reading
frame
A
sequence of codons beginning with an intiation codon and ending with
a termination codon, typically of at least 150 bases (50 amino acids)
coding for a polypeptide or protein chain (see ORF and
URF).
Reagents
Sources
of biological or chemical material that can be used as the starting
blocks in laboratory experiments. Reagents can range from chemicals
needed to perform a particular chemical reaction, constituents of a
laboratory protocol, or clones to be used in a large-scale gene
expression study.
Recessive
Any
trait that is expressed phenotypically only when present on both
alleles of a gene (cf dominant).
Recombinant
DNA (rDNA)
DNA
molecules resulting from the fusion of DNA from different sources.
The technology employed for splicing DNA from different sources and
for amplifying the resultant heterogenous DNA.
Recombination
A new
combination of alleles resulting from the rearrangement occuring by
crossing-over or by independent assortment (see crossing
over).
Recursion
An
algorithmic procedure whereby an algorithm calls on itself to perform
a calculation until the result exceeds a threshold, in which case the
algorithm exits. Recursion is a powerful procedure with which to
process data and is computationally quite efficient.
Regulatory
gene
A DNA
sequence that functions to control the expression of other genes by
producing a protein that modulates the synthesis of their products
(typically by binding to the gene promoter). (cf. Structural
gene).
Relational
Database
A
database that follows E. F. Coddís 11 rules, a series of
mathematical and logical steps for the organization and systemization
of data into a software system that allows easy retrieval, updating,
and expansion. An RDBMS stores data in a database consisting of one
or more tables of rows and columns. The rows correspond to a record
(tuple); the columns correspond to attributes (fields) in the record.
In an RDBMS, a view, defined as a subset of the database that is the
result of the evaluation of a query, is a table. RDBMSs use
Structured Query Language (SQL) for data definition, data management,
and data access and retrieval. Relational and object-relational
databases are used extensively in bioinformatics to store sequence
and other biological data.
Relational
Database Management Systems (RDBMS)
A
software system that includes a database architecture, query
language, and data loading and updating tools and other ancillary
software that together allow the creation of a relational database
application.
Repeats
(repeat sequences)
Repeat
sequences and approximate repeats occur throughout the DNA of higher
organisms (mammals). For example, the Alu sequences of length
about 300 characters, appear hundreds of thousands of times in Human
DNA with about 87% homology to a consensus Alu string. Some
short substrings such as TATA-boxes, poly-A and (TG)* also appear
more often than by chance. Repeat sequences may also occur within
genes, as mutations or alterations to those genes. Repetitive
sequences, especially mobile elements, have many applications in
genetic research. DNA transposons and retroposons are routinely used
for insertional mutagenesis, gene mapping, gene tagging, and gene
transfer in several model systems.
Repetitive
elements
Repetitive
elements provide important clues about chromosome dynamics,
evolutionary forces, and mechanisms for exchange of genetic
information between organisms The most ubiquitous class of repetitive
elements in the DNA sequence in primate genomes is the Alu
family of interspersed repeats which have arisen in the last 65
million years of evolution Alu repeats belong to a class of
sequences defined as short interspersed elements (SINEs).
Approximately 500,000 Alu SINEs exist within the human genome,
representing about 5% of the genome by mass.
Replication
The
synthesis of an informationally identical macromolecule (e.g. DNA)
from a template molecule.
Repressor
The
protein product of a regulatory gene that combines with a specific
operator (regulatory DNA sequence) and hence blocks the transcription
of genes in an operon.
Restriction
enzyme (restriction endonuclease)
A
type of enzyme that recognizes specific DNA sequences (usually
palindromic sequences 4, 6, 8 or 16 base pairs in length) and
produces cuts on both strands of DNA containing those sequences only.
The "molecular scissors" of rDNA technology.
Restriction
fragment length polymorphisms (RFLPs)
Variation
within the DNA sequences of organisms of a given species that can be
identified by fragmenting the sequences using restriction enzymes,
since the variation lies within the restriction site. RFLPs can be
used to measure the diversity of a gene in a population.
Restriction
map
A
physical map or depiction of a gene (or genome) derived by ordering
overlapping restriction fragments produced by digestion of the DNA
with a number of restriction enzymes.
Reverse
Genetics
The
use of protein information to elucidate the genetic sequence encoding
that protein. Used to describe the process of gene isolation starting
with a panel of afflicted patients (see positional
cloning).
Reverse
transcriptase
A DNA
polymerase that can synthesise a complementary DNA (cDNA) strand
using RNA as a template - a so-called RNA-dependent DNA
polymerase.
Reverse
transcriptase-PCR (RT-PCR)
Procedure
in which PCR amplification is carried out on DNA that is first
generated by the conversion of mRNA to cDNA using reverse
transcriptase.
Ribonucleic
acid (RNA)
A
category of nucleic acids in which the component sugar is ribose and
consisting of the four nucleotides Thymidine, Uracil, Guanine, and
Adenine. The three types of RNA are messenger RNA (mRNA), transfer
RNA (tRNA) and ribosomal RNA (rRNA).
Secondary
structure (protein)
The
organization of the peptide backbone of a protein that occurs as a
result of hydrogen bonds e.g alpha helix, Beta pleated
sheet.
Selectivity
Selectivity
of bioinformatics similarity search algorithms is defined as the
significance threshold for reporting database sequence matches. As an
example, for BLAST searches, the parameter E is interpreted as the
upper bound on the expected frequency of chance occurrence of a match
within the context of the entire database search. E may be
thought of as the number of matches one expects to observe by chance
alone during the database search.
Sense
strand
The
strand of double-stranded DNA that acts as the template strand for
RNA synthesis. Typically only one gene product is produced per gene,
reading from the sense strand only. (Some viruses have open reading
frames in both the sense and the antisense strands).
Sensitivity
Sensitivity
of bioinformatics similarity search algorithms centers around two
areas: First, how well can the method detect biologically meaningful
relationships between two related sequences in the presence of
mutations and sequencing errors; Secondly how does the heuristic
nature of the algorithm affect the probability that a matching
sequence will not be detected. At the user's discretion, the speed of
most similarity search programs can be sacrificed in exchange for
greater sensitivity - with an emphasis on detecting lower scoring
matches.
Sequence
Tagged Site (STS)
A
unique sequence from a known chromosomal location that can be
amplified by PCR. STSs act as physical markers for genomic mapping
and cloning.
Sexual
PCR (Molecular Diversity)
Sexual
PCR is a form of PCR in which similar, but not identical, DNA
sequences are reassembled to obtain novel juxtapositions, simulating
the result of genetic recombination. The result is the creation of an
array of related genes which may possess improved characteristics. By
repeated rounds of recombination, selection and PCR-based
amplification vastly improved gene-products, such as enzymes with
greater activity, may be generated and selected.
Shotgun
cloning
The
cloning of an entire gene segment or genome by generating a random
set of fragments using restriction endonucleases to create a gene
library that can be subsequently mapped and sequenced to reconstruct
the entire genome.
Similarity
(homology) search
Given
a newly sequenced gene, there are two main approaches to the
prediction of structure and function from the amino acid sequence.
Homology methods are the most powerful and are based on the detection
of significant extended sequence similarity to a protein of known
structure, or of a sequence pattern characteristic of a protein
family. Statistical methods are less successful but more general and
are based on the derivation of structural preference values for
single residues, pairs of residues, short oligopeptides or short
sequence patterns. The transfer of structure/function information to
a potentially homologous protein is straightforward when the sequence
similarity is high and extended in length, but the assessment of the
structural significance of sequence similarity can be difficult when
sequence similarity is weak or restricted to a short
region.
Signal
sequence (leader sequence)
A
short sequence added to the amino-terminal end of a polypeptide chain
that forms an amphipathic helix allowing the nascent polypeptide to
migrate through membranes such as the endoplasmic reticulum or the
cell membrane. It is cleaved from the polypeptide after the protein
has crossed the membrane.
Single
nucleotide polymorphisms (SNPs)
Variations
of single base pairs scattered throughout the human genome that serve
as measures of the genetic diversity in humans. About 1 million SNPs
are estimated to be present in the human genome, and SNPs are useful
markers for gene mapping studies.
Single-pass
sequencing
Rapid
sequencing of large segments of the genome of an organism by
isolating as many expressed (cDNA) sequences as possible and
performing single sequencer runs on their 5í or 3í
ends. Single-pass sequencing typically results in individual,
error-prone sequencing reads of 400-700 bases, depending on the type
of sequencer used. However, if many of these are generated from
numerous clones from different tissues, they may be overlapped and
assembled to remove the errors and generate a contiguous sequence for
the entire expressed gene.
Site
Sites
in sequences can be located either in DNA (e.g. binding sites,
cleavage sites) or in proteins. In order to identify a site in DNA,
ambiguity symbols are used to allow several different symbols at one
position. Proteins, however, need a different mechanism (see
Pattern). Restriction enzyme cleavage sites, for instance, have the
following properties: limited length (typically, less than 20
base pairs); definition of the cleavage site and its appearance (3',
5' overhang or blunt); definition of the binding site.
Southern
blotting
A
procedure for the identification of DNA by transmitting a fragment
isolated on an agarose gel to a nitrocellulose filter where it can be
hybridized with a complementary "probe" sequence.
Splice
site
The
sequence found at the 5í and 3í region of exon/intron
boundaries, usually defined by a consensus sequence:
Intron
5í
CAGGTAAGT---------TNCAGG 3í
A G C
T
N
represents any nucleotide; the bottom line represents alternative
nucleotides at the indicated positions.
Splice
form
By
using alternative splicing, a single message precursor from DNA can
generate an entire family of mRNAs and proteins. This can be utilized
to create specificity in cell-cell or cell-ligand interactions. A
cell may produce a given protein, but it will be a different
splice-form of the protein than that produced by an adjacent cell. In
this manner, the two cells have the potential to interact differently
with other cells or molecules. Two places where this has been
extremely important is in the production of cell-surface specificity
proteins in the immune and nervous systems.
Splicing
The
joining together of separate DNA or RNA component parts. For example,
RNA splicing in eukaryotes involves the removal of introns and the
stitching together of the exons from the pre-mRNA transcript before
maturation.
Solvent
accessibility
The
surface area (typically measured in square angstroms) of a biological
molecule, usually a protein, that is exposed to solvent in its
native, folded form. Determining the solvent accessibility of a
protein helps define which amino acids in its molecular sequence are
on the exterior of the molecule, and thus available to participate in
interactions with other molecules.
Structural
gene
Gene
which encodes a structural protein (cf. Regulatory gene).
Structure
prediction
Algorithms
that predict the secondary, tertiary and sometimes even quarternary
structure of proteins from their sequences. Determining protein
structure from sequence has been dubbed "the second half of the
Genetic Code" since it is the folded tertiary structure of a protein
that governs how it functions as a gene product. As yet most
structure prediction methods are only partially successful, and
typically work best for certain well-defined classes of
proteins.
Substitution
matrix
A
model of protein evolution at the sequence level resulting in the
development of a set of widely used substitution matrices. These are
frequently called Dayhoff, MDM (Mutation Data Matrix), BLOSUM or PAM
(Percent Accepted Mutation) matrices. They are derived from global
alignments of closely related sequences. Matrices for greater
evolutionary distances are extrapolated from those for lesser
ones.
Subtraction
library
A
cDNA library that only contains cDNAs uniquely expressed in a given
cell or tissue. e.g T cells and B cells will express many common
RNAs, as well as a very small percentage which will be unique for T
cells and B cells respectively. To make a T cell subtraction library,
the cDNA from a T cell library is hybridized with a vast excess of B
cell RNA. The commonly expressed genes will result in RNA-cDNA
hybrids which can be removed (or subtracted) to leave only T cell
specific cDNAs.
Tentative
Consensus (TC)
The
identification of a sequence from an EST cluster that represents part
or all of a complete gene. TCs are usually determined by
clustering ESTs allowing for sequencing errors, artefacts such as
chimeric clones, and naturally occuring biological phenomena such as
alternative splicing. Creation of a cluster allows one to
generate a consensus sequence and then identify a long open reading
frame which would suggest the possibility of that consensus
representing a bona fide gene.
Tentative
Human Consensus sequences (THCs)
A
consensus sequence generated from human EST fragments. THCs may be
validated by comparison against databases of known human gene
sequences, human genomic sequences, or by identification of the ORFs
or other sequence features contained within the consensus as
belonging to a known human gene product.
Tertiary
structure
Folding
of a protein chain via interactions of its sideschain molecules
including formation of disulphide bonds between cysteine
residues.
Thymine
A
pyrimidine base found in DNA but not in RNA.
Tissue
Section
of an organ that consists of a largely homogenous population of cell
types. Since many organs are multifunctional, they have developed
highly specialized cell types to perform different functions.
Identifying the section of an organ that is homogenous for a
particular cell type ensures that the gene expression profiles
extracted from those cells will accurately resemble the class of
cells that make up the tissue.
Transcript
The
single-stranded mRNA chain that is assembled from a gene
template.
Transcription
The
assembly of complementary single-stranded RNA on a DNA
template.
Transcription
factors
A
group of regulatory proteins that are required for transcription in
eukaryotes. Transcription factors bind to the promoter region of a
gene and facilitate transcription by RNA polymerase.
Transfer
RNA (tRNA)
A
small RNA molecule that recognizes a specific amino acid, transports
it to a specific codon in the mRNA, and positions it properly in the
nascent polypeptide chain.
Transformation
A
genetic alteration to a cell as a result of the incorporation of DNA
from a genetically diferent cell or virus; can also refer to the
introduction of DNA into bacterial cells for genetic
manipulation.
Transgene
A
foreign gene that is introduced into a cell or whole organism
(eg.transgenic mice) for therapeutic or experimental
purposes.
Translation
The
process of converting RNA to protein by the assembly of a polypeptide
chain from an mRNA molecule at the ribosome.
Transmembrane
region
The
region of a transmembrane protein that actually spans the
membrane. Transmembrane regions are usually hydrophobic in
order to be thermodynamically compatible with the lipid bilayer
portion of the membrane. They may consist of either
alpha-helical or beta-strand secondary structure elements, but in
either case the external residues (the ones facing the membrane) are
invariably hydrophobic while the internal residues may be hydrophilic
(as in the case of a pore or channel) or polar. One common
transmembrane structural domain is the seven-helix bundle seen in
numerous channel proteins.
Tissue
Section
of an organ that consists of a largely homogenous population of cell
types. Since many organs are multifunctional, they have developed
highly specialized cell types to perform different functions.
Identifying the section of an organ that is homogenous for a
particular cell type ensures that the gene expression profiles
extracted from those cells will accurately resemble the class of
cells that make up the tissue.
Unidentified
reading frame (URF)
An
open reading frame encoding a protein of undefined
function.
Uracil
Nitrogenous
pyrimidine base found in RNA but not DNA.
Variable
numbers of tandem repeats (VNTRs)
DNA
sequence blocks of 2-60 base pairs which are repeated from two to
more than 20 times in different individuals. This polymorphism makes
VNTRs very useful DNA markers used in genomic mapping, linkage
analysis and also DNA fingerprinting.
Variation
(genetic)
Variation
in genetic sequences and the detection of DNA sequence variants
genome-wide allow studies relating the distribution of sequence
variation to a population history. This in turn allows one to
determine the density of SNPS or other markers needed for gene
mapping studies. Quantitation of these variations together with
analytical tools for studying sequence variation also relate genetic
variations to phenotype.
Vector
Any
agent that transfers material (typically DNA) from one host to
another. Typically DNA vectors are autonomous DNA elements (such as
plasmids) that can be manipulated and integrated into a hostís
DNA or recombinant viruses.
Virtual
libraries
The
creation and storage of vast collections of molecular structures in
an electronic database. These databases may be queried for subsets
that exhibit specific physicochemical features, or may be "virtually
screened" for their ability to bind a drug target. This process may
be performed prior to the synthesis and testing of the molecules
themselves.
Visualization
Visualization
is the process of representing abstract scientific data as images
that can aid in understanding the meaning of the data.
Weight
matrix
The
density of binding sites in a gene or sequence can be used to derive
a ratio of density for each element in a pattern of interest. The
combined individual density ratios of all elements are then
collectively used to build a scoring profile known as a weight
matrix. This profile can be used to test the prediction of the
identification of the selected pattern and the ability of the
algorithm to discriminate them from non-pattern sequences.
Western
blot
Technique
in which specific antibodies are used to identify their antigens from
a mixture of proteins. Typically, these proteins mixtures are first
separated by electrophoresis and then transfered onto nylon sheets by
electrotransfer. Radiolabeled or enzyme-linked antibodies are
incubated with the sheets and unbound antibodies washed away allowing
the position of the bound antibody to be revealed by autoradiography
or color which is formed upon addition of a substrate.
Wild
type
Form
of a gene or allele that is considered the "standard" or most
common.
X
chromosome
In
mammals, the sex chromosome that is found in two copies in the
homogametic sex (female in humans) and one copy in the hererogametic
sex (male in humans).
Yeast
2-hybrid system
A
yeast-based method used to simultaneously identify, and clone the
gene for, proteins interacting with a known protein. The basis of
this method is a "transcriptional reporter assay" (see definition) in
which reporter gene expression is dependent on two domains. The first
domain is linked to the known protein. The second domain is
genetically linked to a library. If the library is screened against
the known protein the two domains will interact only if a protein
from the library binds the known protein, resulting in transcription
activation of the reporter gene, and a blue color. The "blue yeast
clone" will contain the gene encoding the newly identified
protein.
Z-DNA
A
conformation of DNA existing as a left-handed double helix (the
phosphate-sugar backbone forms a left-handed zig-zag course), which
may play a role in gene regulation.
Zinc
fingers
A
protein motif formed by the interaction of repeated cysteine and
histidine residues with a zinc ion. The spacing of the repeats
results in finger like arrangements of the protein loops formed from
the interaction which interact with DNA. These motifs are typically
found in transcription factors.
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