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( A-C ) ( D - H) ( I M) (N -R ) (S- T ) (U-Z )
N
Pure, isolated DNA devoid of any proteins that may bind to it.
Compounds identified as potential drugs that are sent from research and development into clinical trials to determine their suitability.
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.
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.
A point mutation in which a codon specific for an amino-acid is converted into a nonsense codon.
A technique to identify RNA molecules by hybridization that is analogous to Southern blotting (see Southern blotting).
Any enzyme that can cleave the phosphodiester bonds of nucleic acid backbones.
A five-carbon sugar covalently attached to a nitrogen base.
A nucleic acid unit composed of a five carbon sugar joined to a phosphate group and a nitrogen base.
O
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.
A short molecule consisting of several linked nucleotides (typically between 10 and 60) covalently attached by phosphodiester bonds.
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.
A segment of DNA that interacts with the products of regulatory genes and facilitates the transcription of one or more structural genes.
A unit of transcription consisting of one or more structural genes, an operator, and a promoter.
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.)
Collection of cloned sequences made by generating randomly overlapping DNA fragments with infrequently cutting restriction enzymes.
P
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 5' GAATTC 3' whose complementary sequence is 3' CTTAAG 5'.
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.
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.
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 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.
A short stretch of amino acids each covalently coupled by a peptide (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).
A virus that infects bacterial cells and serves as a useful vector for introducing genes into bacteria for a number of purposes.
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.
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.
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.
Any observable feature of an organism that is the result of one or more genes.
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.
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.
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.
The multiple effects on an organism's 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.
A mutation in which a single nucleotide in a DNA sequence is substituted by another nucleotide.
The stretch of Adenine (A) residues at the 3' 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.
A site on the 3'-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.
Inheritance involving alleles at many genetic loci.
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.
(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).
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.
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.
Alterations made to pre-mRNA before it leaves the nucleus and becomes mature mRNA.
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.
The linear sequence of a polypeptide or protein.
see primary sequence.
A short oligonucleotide that provides a free 3' hydroxyl for DNA or RNA synthesis by the appropriate polymerase (DNA polymerase or RNA polymerase).
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.
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.
An organism or cell that lacks a membrane-bounded nucleus. Bacteria and blue-green algae are the only surviving prokaryotes (cf. Eukaryote).
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.
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.
The entire protein complement of a given organism.
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)
A nitrogen-containing compound with a double-ring structure. The parent compound of Adenine and Guanine.
A nitrogen-containing compound with a single six-membered ring structure. The parent compound of Thymidine and Cytosine.
Q
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.
R
The development of drugs based on the 3-dimensional molecular structure of a particular target.
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).
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.
Any trait that is expressed phenotypically only when present on both alleles of a gene (cf dominant).
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.
A new combination of alleles resulting from the rearrangement occuring by crossing-over or by independent assortment (see crossing over).
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.
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).
A database that follows E. F. Codd's 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.
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.
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 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.
The synthesis of an informationally identical macromolecule (e.g. DNA) from a template molecule.
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.
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.
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.
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.
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).
A DNA polymerase that can synthesise a complementary DNA (cDNA) strand using RNA as a template - a so-called RNA-dependent DNA polymerase.
Procedure in which PCR amplification is carried out on DNA that is first generated by the conversion of mRNA to cDNA using reverse transcriptase.
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).