The transcriptomics section of this guide provides definitions and resources for transcriptomics related terms.
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(Alternative phrasing) - These are alternative phrases for the terms, which can be synonyms, acronyms, or other ways of referring to the concept.
[See also] - These are terms that are related to the defined term.
The type of transactivation domain found in transcriptional activators such as Gal4. This domain contains a stretch of acidic amino acids and is required for interactions with co-activators.
A post-transcriptional gene regulation mechanism in eukaryotes in which multiple protein products are produced by a single gene through alternative splicing combinations of the RNA transcript.
RNAs that bind segments of mRNA in trans to inhibit translation.
Oligonucleic acids that bind to a specific target molecule, such as a small molecule, protein or nucleic acid. Nucleic acid aptamers are typically developed through in vitro selection schemes but are also found naturally (for example, RNA aptamers in riboswitches).
Effector proteins of small RNA-directed silencing. Small RNAs guide Argonautes to their RNA targets. Argonaute proteins are characterized by two domains PIWI (a ribonuclease domain) and Piwi Argonaute and Zwille (PAZ; an ssRNA-binding module).
A method for enriching whole genomic DNA for many regions of interest by hybridization to an array containing RNA or DNA sequences complementary to the regions of interest.
ATP-dependent nucleosome-remodelling complex
A transcriptional regulatory complex that uses the energy obtained from ATP hydrolysis to move or displace histone octamers from DNA.
A conserved mRNA splicing mechanism. It is composed of the splicing signals and the core of the machinery is formed by five spliceosomal small nuclear ribonucleoproteins and an unknown number of proteins.
A system used by most next-generation sequencing platforms. When a one-base-encoded probe or a sequencing-by-synthesis approach is used, each signal is correctly correlated to a base.
A framework of statistical inference in which previous beliefs (or data) and likelihoods are combined to estimate a parameter of interest given the observed data.
A statistical perspective that focuses on the probability distribution of parameters before and after observing the data.
Refers to two (possibly different) variants located on both alleles of the same gene.
An individual protein that is uniquely produced in a diseased state.
The use of artificial methods to modify the genetic material of living organisms or cells to produce novel compounds or to perform new functions.
When n statistical tests are carried out, each has the potential (probability, p, the significance level) to return a false-positive result. If tests are independent of each other, the so-called experiment-wise probability that one or more tests show a false-positive result is approximately np. So, to achieve an experiment-wise false-positive rate of p, each individual test must only be allowed a false-positive error rate of p/n, which is referred to as the Bonferroni correction.
A statistical approach that is often used to generate confidence intervals (measures of variation) around parameter estimates in which the data are re-sampled repeatedly (with replacement) using computer Monte Carlo simulations.
A conserved structural domain of ~40–50 amino acids that is commonly found in proteins associated with chromatin remodeling and with proteins that bind to acetylated lysine residues in histones.
Nuclear bodies that are associated with the maturation of ribonucleoprotein complexes.
Cap Analysis of Gene Expression
The high-throughput sequencing of concatamers of DNA tags that are derived from the initial nucleotides of 5′ mRNA.
A zinc-finger protein associated with diverse context-dependent effects on transcription.
An ATP-dependent enzymatic process that alters histone–DNA interactions or regulates the position of nucleosomes. Chromatin remodelling can also be ATP-independent in the case of the facilitates chromatin transcription (FACT) complex.
The propensity of transcription factors (TFs) to be inhibited from binding motifs due to reversible chromatin features such as modification of DNA (CpG methylation) or presence and actions of chromatin proteins (such as nucleosomes).
Specific, largely non-overlapping areas in the nucleus that each chromosome occupies.
Chromosome-associated regulatory RNAs
Regulatory RNAs associated with the chromatin.
(carRNAs)
Non-coding DNA sequences that regulate transcription of genes located on the same chromosome. They include enhancers, promoters, insulators, silencing elements and tethering elements. Different classes of CREs can be identified using a combination of molecular markers, including chromatin accessibility and epigenetic modifications.
(CRE, CREs)
The production of an exact copy—specifically, an exact genetic copy—of a gene, cell, or organism.
A mathematical algorithm that organizes a set of items according to their similarity. For example, genes can be clustered according to their similarity in pattern of expression.
Groups of DNA templates in close spatial proximity, generated either though bead-based amplification or by solid-phase amplification. Bead-based approaches rely on emulsions to maintain template isolation during amplification. Solid-phase approaches rely on the template-to-bound-adapter ratio to probabilistically bind template molecules at a sufficient distance from each other.
The joining of genetic lineages to common ancestors when they are traced backwards in time.
The portion of a gene or an mRNA which actually codes for a protein.
(Coding sequence, CDS)
Genetic markers that allow the determination of both alleles at a diploid locus (for example, microsatellites, allozymes and single nucleotide polymorphisms); these differ from dominant markers in which the determination of heterozygotes is not always possible (or example, RAPDs and AFLPs).
A codon is a sequence of three DNA or RNA nucleotides that corresponds with a specific amino acid or stop signal during protein synthesis.
A multisubunit protein complex that mediates sister-chromatid cohesion in mitosis and is essential for topologically associating domain (TAD) formation.
Comparative anchor-tag sequences
Exon sequences that are conserved across taxa allowing the design of primers that amplify in divergent species (for example, across mammal orders). CATS-like primers speed the discovery of SNPs (in exons or introns) and comparative genome mapping across taxa.
(CATS)
A spurious association between a risk factor (a gene, exposure or interaction) and disease induced by the joint associations of some other variable with the risk factor and the disease that are independent of the risk factor. Confounding can also distort the magnitude of the association of a true risk factor with disease or mask it.
The transfer of genetic information from a donor to a recipient cell by a conjugative or mobile genetic element, often a conjugative plasmid.
Algorithms designed to learn from the data to uncover connections. CNNs are frequently used in image recognition and have been increasingly used to uncover relationships in biological data.
(CNN, CNNs)
The number of sequence reads that have alignments that overlap a certain position. Because current sequencing strategies produce random reads, resulting in an uneven distribution of reads across the genome, a high average coverage is required to assure that most bases in the genome are covered by multiple reads.
A sequence of at least 200 bp with a greater number of CpG sites than expected for its GC content. These regions are often GC rich, typically undermethylated, and are found upstream of many mammalian genes.
(Recombination)
The CCCTC binding factor (CTCF) is a zinc-finger transcription factor that is enriched at the boundaries of TADs.
An RNase III family endonuclease that processes dsRNAs into small interfering RNAs.
The conversion of a continuous signal to a discrete signal.
Classical statistical pattern-recognition methods that are used to categorize samples into two classes of data.
A form of selection in which extreme phenotypes are more fit than intermediate forms.
The process of genetically adapting an animal or plant to better suit the needs of human beings (for example, breeding cattle for milk production).
A visualization technique that allows the easy identification of matching nucleotides or amino acids (letters) between two sequences. For example, for two sequences X and Y, each letter has a unique coordinate on the x axis and the y axis respectively. When two letters are the same at a specified coordinate, a dot is plotted in the matrix at that position.
A twofold rotational symmetry relationship (in this case, a DNA arrangement in which a 5′→3′ sequence on one strand is juxtaposed with the same 5′→3′ sequence on the opposite strand). Transcripts from such regions have the capacity to form stem–loop structures.
Recombination between nonhomologous sequences.
The increase in risk (or proportion of population variation) that is conferred by a given causal variant.
The size of the ideal constant-size population, in which the effects of random drift would be the same as those seen in the actual population.
(Ne)
The prevalent endogenous viral elements that are derived from retroviruses that have become integrated into the genome.
(ERV RNAs, ERVs, ERV RNA)
An intermediate phenotype that is heritable and associated with a disease but is not itself a symptom of the disease. Although there is little evidence to support the theory, it has been argued that endophenotypes would be a more tractable target for genetic analysis than the relevant disease state itself.
Interactions driven by the binding energy between molecules, such as homotypic interactions among chromatin states.
Changes that increase the number of accessible microstates in the system and do not require input energy.
Environment-responsive promoters
Promoters that directly transduce environmental signals (for example, heavy metal ions, hormones, chemicals or temperature) that are captured by their associated sensory transcription factors.
Epidermal differentiation complex
A gene complex of >50 genes that encode proteins involved in terminal differentiation and cornification of skin epidermal keratinocytes.
(EDC)
Literally means 'outside conventional genetics'; this term describes any heritable change in gene expression that is not caused by a change in DNA sequence.
The state of those mechanisms that regulate gene expression and are transmitted to daughter cells.
In the context of transient transfection, this term refers to a plasmid target that is extra chromosomal.
Features (such as feathers) that evolved by selection for one purpose (such as warmth) and were later adapted to a new purpose (such as flight).
The exome is the collection of known exons in our genome: this is the portion of the genome that is translated into proteins. As exons comprise only 1% of the genome and contain the most easily understood, functionally relevant information, sequencing of only the exome is a cheaper method of identifying most of the variants that are most likely to affect a trait.
Exon-primed intron-crossing PCR
EPIC primers are designed in conserved exons and amplify intron sequences that are generally more polymorphic than exons, which are therefore useful for the development of SNP or RFLP markers.
(EPIC-PCR, EPIC PCR)
The rate of phenotypic change that results from the continuing accumulation of new mutations (expressed mutation rate = total mutation rate − neutral mutation rate).
Short DNA sequences (several hundred base pairs) that are produced by reverse transcription of mRNA into DNA. ESTs are cDNAs that consist of exons and the sequences that flank exons. The sequencing of ESTs allows rapid identification ('tagging') of genes and can expedite DNA marker (SNP) development in coding genes.
(EST, ESTs)
Reversibly condensed chromatin conformation that is transcriptionally silent.
The proportion of false-positive test results out of all positive (significant) tests (note that the FDR is conceptually different to the significance level).
(FDR)
A study design in which many members of a family across several generations are sequenced. These studies are used to understand how phenotypes manifest within a particular genotype background.
Markers used to correct for drift that may occur during an experiment. These can be fluorescent beads or labels on the DNA that remain constant throughout the imaging experiment.
Disposable parts of a next-generation sequencing routine. Template DNA is immobilized within the flow cell where fluid reagents can be streamed into the cell and flushed away.
Fluorescence resonance energy transfer
A system in which energy can be transferred from one light-sensitive molecule to another. When the two molecules are in close proximity (≤30 nm), energy transferred between the two molecules modulates the intensity of a fluorescence signal.
(FRET, Förster resonance energy transfer, Forster resonance energy transfer)
If all four possible gametes are observed for two bi-allelic loci then this test infers that a recombination event must have occurred between them (under an infinite sites mutation model).
(FGT)
Fourier transform infrared spectroscopy
A spectroscopy method that simultaneously collects the absorption, emission and photoconductivity of a wide spectral range at high resolution to measure the intensity and wavelength of light required to vibrate molecules in a sample.
The process of breaking large RNA fragments into smaller fragments. This can be achieved mechanically (by passing the RNA through a narrow passage), by sonication or enzymatically.
A genomic sequence that provides a function that is under selection and tends to be conserved between species. For example, a protein-coding region or transcription-factor binding site.
Alignment programs deal with insertions and deletions (indels) by introducing a 'gap' in the sequence that contains the deletion. The introduction of gaps and their extension decreases the overall alignment score by a certain value. This value is defined by a gap-opening penalty and a gap-extension penalty, both of which are used as parameters in alignment programs.
A technique used to separate molecules on the basis of their ability to migrate through a semisolid gel in response to an electric current.
General transcription machinery
RNA polymerase II together with the general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH.
An organism whose genome has been artificially changed.
(GMO)
The simultaneous genotyping of hundreds of loci from across the genome, which ideally includes mapped loci and different classes of loci such as allozymes, microsatellites and AFLPs, or synonymous (non-coding) and non-synonymous nucleotide polymorphisms.
An examination of common genetic variation across the genome that is designed to identify associations with traits, such as common diseases.
(GWAS)
Epigenetic marks that are differentially established during male and female gametogenesis and lead to allele-specific gene expression after fertilization.
Selection on traits that increase the relative fitness of populations or lineages of organisms at some fitness cost to individuals. All of the feasible mechanisms require selection on lineages or small interbreeding groups of related individuals in subdivided populations.
Helicos Genetic Analysis System
A sequencing technology based on single nucleotide addition. Each nucleotide contains a ‘virtual terminator’ that prevents the incorporation of multiple nucleotides per cycle.
The proportion of total phenotypic variation that can be attributed to genetic effects (broad sense) or purely additive genetic effects (narrow sense). Narrow-sense heritability predicts the initial response of a population to selection and decreases over the course of selection.
A phenotype that is at least partially transmitted genetically from parents to offspring.
A densely packaged form of chromatin that is associated with repressive histone modifications, DNA methylation and gene silencing.
A probabilistic model that is applied to protein- and DNA-sequence pattern recognition. HMMs represent a system as a set of discrete states and as transitions between those states. Each transition has an associated probability. HMMs are valuable because they enable a search or alignment algorithm to be built on firm probabilistic bases, and the parameters (transition probabilities) can be easily trained on a known data set.
(HMM)
A family of small, highly conserved basic proteins that are found in the chromatin of all eukaryotic cells and that associate with DNA to form a nucleosome. Two each of the core histones H2A, H2B, H3 and H4 make up an octameric nucleosome, around which DNA winds.
Covalent modifications to histone proteins, such as methylation, acetylation, phosphorylation, ubiquitylation and sumoylation, that take place at lysine, serine, threonine, arginine and other residues. Histone modifications are catalysed by a diverse panel of enzymes referred to as writers, removed by a different set of proteins known as erasers, and recognized by chromatin-binding proteins known as readers. Activity of CREs is directly linked to distinct histone modifications due to the activities of writers, erasers and readers.
Histone octamer lateral surface
The positively charged outer surface of the histone octamer around which DNA is wrapped.
Structurally distinct, non-typical versions of histone proteins. They are encoded by independent genes and are often subject to regulation that is distinct from that of the canonical histones.
A technique similar to ChIP–seq in which proteins bound to RNA — such as splicing factors — are immunoprecipitated and the RNA fragments are sequenced.
A sequence run of identical bases.
An alternative base pairing in which the purine is flipped and form different hydrogen bonds with partner bases. For adenines, the second hydrogen bond with the pyrimidine base is formed with N6 rather than N1. These alternative base pairs allow for additional structures beyond double helix including triplexes and quadruplexes.
A group of linked regulatory homeobox genes that are involved in patterning the animal body axis during development. Homeobox genes are defined as those that contain an 180-base-pair sequence that encodes a DNA-binding helix–lturn–helix motif (a homeodomain).
Offspring that are produced by crossing two different populations within a single species.
Low activity of forms of a gene.
Refers to a variant that results in reduced but not eliminated function of the gene product.
Two or more alleles are identical by descent if they are identical copies of the same ancestral allele.
Two or more alleles are identical by state if they are identical. Alleles which are identical by state may or may not be identical by descent owing to the possibility of multiple mutation events.
A locus with monoallelic expression determined by the parental origin of the allele.
The epigenetic marking of a gene on the basis of parental origin, which in somatic tissues results in monoallelic expression.
Refers to the phenomenon of some individuals who carry a pathogenic variant who do not exhibit clinical signs.
A small insertion or deletion of nucleotides. If it occurs in an exon and is not a multiple of three in length, it results in a frameshift and usually the loss of gene function.
A model that assumes that there are an infinite number of nucleotide sites and consequently that each new mutation occurs at a different locus.
The tendency of different traits to vary jointly in a coordinated manner throughout a morphological structure or even a whole organism.
The ratio of odds ratios for the relationship of one factor (for example, a gene) with disease across the levels of another factor (for example, an environmental exposure); as such, it is a measure of departure from a multiplicative joint effect.
A set of molecular components of the cell, such as proteins, and the interactions between them. The interactions can be physical (protein A binds protein B) or correlative (perturbing protein A alters protein B's activity).
A phenomenon in which the occurrence of a crossover recombination at one position on a chromosome suppresses the frequency of additional, nearby crossovers; inhibition decreases with physical distance.
The relative position of an intron within or between codons. Phase zero, one and two are defined by the position of an intron between two codons or after the first or second nucleotide of a codon, respectively.
Proteins produced from the same genetic locus but which differ in exon order or combination.
Pairs of structurally distinct restriction enzymes with the same recognition sequence and the same cleavage positions.
The non-random association of alleles. For example, alleles of SNPs that reside near one another on a chromosome often occur in non-random combinations owing to infrequent recombination. Linkage disequilibrium is useful in genome-wide association studies as it reduces the number of SNPs that must be interrogated to determine genotypes across the genome. Conversely, strong linkage disequilibrium can complicate the identification of functional variants.
(LD)
Reads derived from the 10X Genomics synthetic long-read platform. These are discontinuous reads each sharing the same barcode, thus they are derived from the same original long molecule.
This occurs when a phenotype is caused by mutations at more than one gene locus, which suggests that the products of the genes belong to the same metabolic pathway.
The logarithm of the likelihood ratio (odds) for genetic linkage versus no linkage at a given value of the recombination fraction.
(Logarithm of odds score)
A statistical model for the dependency of a binomial (two-class) phenotype on a number of risk factors. The probability, p, for one of the two phenotype states is expressed in the form of its logit, log(p/(1 – p)), which is assumed to be predicted by the linear combination (weighted sum) of the risk factors.
Non-coding RNAs longer than 200 nucleotides.
(lncRNA, lncRNAs)
A model of how CTCF and cohesin are thought to form topologically associating domains (TADs), whereby cohesin is loaded onto the DNA and extrudes a loop until it is blocked by CTCF bound at the base of the loop.
An approach to genetic association studies that is focused on putatively functional SNPs, for example, identified by re-sequencing exons and other functional regions in relatively large samples, or directly in patients. This approach is also sometimes called direct.
The effects of a specific risk factor (gene or exposure) in the population as a whole, averaging over all other variables.
The process by which new genetic markers are obtained — for example, by re-sequencing a subset of chromosomes in a population sample. If those markers are population-specific then inferences that are based on them in other populations might be biased through so-called ascertainment bias.
A computational technique for the efficient numerical calculation of likelihoods.
(MCMC)
A method that selects the phylogenetic tree that has the highest probability of explaining the sequence data, under a specific model of substitution (changes in the nucleotide or amino-acid sequence).
A statistical test that is commonly used for the comparison of between-species divergence and within-species polymorphism at replacement and synonymous sites to infer adaptive protein evolution.
A multisubunit protein complex that bridges transcription factors and the basal RNA polymerase II transcriptional machinery.
A disease that is carried in families in either a dominant or recessive manner and that is typically controlled by variants of large effect in a single gene.
A technique for studying the relationship between a biomarker and disease indirectly by studying the relationship of each to a gene that influences the biomarker.
Refers to transcription factor (TF) motifs that are bound with higher affinity when CpG dinucleotides within the motif are methylated.
Refers to transcription factor (TF) motifs that are bound with lower affinity when CpG dinucleotides within the motif are methylated.
Evolutionary processes or changes over relatively short time periods — such as change in allele frequencies, genotypic composition or gene expression — within or between populations.
The small nuclear structures that reside in the cytoplasm and contain damaged DNA fragments which were not incorporated into the main nucleus after mitosis.
Ranging from 0 to 50%, this is the proportion of alleles at a locus that consists of the less frequent allele. This number does not take genotype into account.
(MAF)
A protein complex involved in the early stages of processing microRNA (miRNA) and RNA interference in animal cells.
A heterogeneous complex composed of mitochondrial RNA and proteins involved in RNA regulation.
(MRG, MRGs)
Molecular mechanism driving circadian rhythms, consisting of transcriptional–translational feedback loops of core clock genes.
The use of molecular genetic techniques — for example, multiplex PCR, pulse-field gel electrophoresis, Southern blotting and multilocus sequence typing — to genetically compare and characterize bacterial genomes.
A condition in which an animal contains multiple cell lineages with different genotypes.
The accumulated deleterious alleles that are carried by a population at any given time.
A region in which the frequency of mutation is greater than expected, owing to specific structural and/or functional features of the protein or gene.
Mutually exclusive alternative splicing
Only one of a set of two or more exons in a gene is included in the final transcript.
The process by which the cell destroys mRNAs that are untranslatable due to the presence of a premature stop codon in the coding region.
A large family ofDNA-binding transcription factors that are responsible for sensing various hormonal and environmental stimuli and mediating gene expression accordingly.
A subnuclear region in which components of the translational machinery are synthesized. It is a site of abundant transcription by RNA polymerase I and III.
Small germ-cell RNAs that interact with PIWI proteins. They are thought to be involved in the repression of retrotransposon expression during gametogenesis.
A 44 polypeptide complex, which consists of RNA polymerase II and the general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH. Its formation at TATA-containing core promoters is nucleated by binding of TATA-binding protein (a component of TFIID) to the TATA element in the promoter DNA sequence.
Precursor mRNA sequences that resemble exons — both in their size and in the presence of flanking splice-site sequences — but that are not normally recognized by the splicing machinery.
A cell-to-cell communication mechanism in many species of bacteria, whereby cells measure their local density (by the accumulation of a signalling molecule) and subsequently coordinate gene expression.
Small regulatory RNAs that can activate or repress gene expression by binding segments of mRNA in trans. They are typically expressed in response to an environmental signaling event.
A plant-specific pathway through which small RNAs (24 nucleotides long) target the de novo methyltransferase DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) to homologous genomic loci to establish DNA methylation, which leads to transcriptional gene silencing.
A process of post-transcriptional gene silencing in which small RNAs, often generated by the activity of an RNA-dependent RNA polymerase and a Dicer endoribonuclease, are bound by Argonaute proteins and target cleavage of homologous mRNA transcripts.
RNA isolated from cells are sequenced by next-generation sequencing after conversion to cDNA.
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