High-content screeningHigh-content screening (HCS), also known as high-content analysis (HCA) or cellomics, is a method that is used in biological research and drug discovery to identify substances such as small molecules, peptides, or RNAi that alter the phenotype of a cell in a desired manner. Hence high content screening is a type of phenotypic screen conducted in cells involving the analysis of whole cells or components of cells with simultaneous readout of several parameters.
High-throughput screeningHigh-throughput screening (HTS) is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handling devices, and sensitive detectors, high-throughput screening allows a researcher to quickly conduct millions of chemical, genetic, or pharmacological tests. Through this process one can quickly recognize active compounds, antibodies, or genes that modulate a particular biomolecular pathway.
Dose–response relationshipThe dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure (or doses) to a stimulus or stressor (usually a chemical) after a certain exposure time. Dose–response relationships can be described by dose–response curves. This is explained further in the following sections. A stimulus response function or stimulus response curve is defined more broadly as the response from any type of stimulus, not limited to chemicals.
Drug discoveryIn the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by serendipitous discovery, as with penicillin. More recently, chemical libraries of synthetic small molecules, natural products or extracts were screened in intact cells or whole organisms to identify substances that had a desirable therapeutic effect in a process known as classical pharmacology.
Phenotypic screeningPhenotypic screening is a type of screening used in biological research and drug discovery to identify substances such as small molecules, peptides, or RNAi that alter the phenotype of a cell or an organism in a desired manner. Phenotypic screening must be followed up with identification (sometimes referred to as target deconvolution) and validation, often through the use of chemoproteomics, to identify the mechanisms through which a phenotypic hit works. Phenotypic screening historically has been the basis for the discovery of new drugs.
Schild equationIn pharmacology, Schild regression analysis, based upon the Schild equation, both named for Heinz Otto Schild, are tools for studying the effects of agonists and antagonists on the response caused by the receptor or on ligand-receptor binding. Dose-response curves can be constructed to describe response or ligand-receptor complex formation as a function of the ligand concentration. Antagonists make it harder to form these complexes by inhibiting interactions of the ligand with its receptor.
Classical pharmacologyIn the field of drug discovery, classical pharmacology, also known as forward pharmacology, or phenotypic drug discovery (PDD), relies on phenotypic screening (screening in intact cells or whole organisms) of chemical libraries of synthetic small molecules, natural products or extracts to identify substances that have a desirable therapeutic effect. Using the techniques of medicinal chemistry, the potency, selectivity, and other properties of these screening hits are optimized to produce candidate drugs.
Sequence homologySequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speciation event (orthologs), or a duplication event (paralogs), or else a horizontal (or lateral) gene transfer event (xenologs). Homology among DNA, RNA, or proteins is typically inferred from their nucleotide or amino acid sequence similarity.
Therapeutic indexThe therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. The related terms therapeutic window or safety window refer to a range of doses optimized between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity.
OrganismAn organism () is any biological living system that functions as an individual life form. All organisms are composed of cells (cell theory). The idea of organism is based on the concept of minimal functional unit of life. Three traits have been proposed to play the main role in qualification as an organism: noncompartmentability – structure that cannot be divided without its functionality loss, individuality – the entity has simultaneous holding of genetic uniqueness, genetic homogeneity and autonomy, distinctness – genetic information has to maintain open-system (a cell).
Morphology (biology)Morphology is a branch of biology dealing with the study of the form and structure of organisms and their specific structural features. This includes aspects of the outward appearance (shape, structure, colour, pattern, size), i.e. external morphology (or eidonomy), as well as the form and structure of the internal parts like bones and organs, i.e. internal morphology (or anatomy). This is in contrast to physiology, which deals primarily with function.
Multicellular organismA multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism. All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni- and partially multicellular, like slime molds and social amoebae such as the genus Dictyostelium. Multicellular organisms arise in various ways, for example by cell division or by aggregation of many single cells. Colonial organisms are the result of many identical individuals joining together to form a colony.
Homology (biology)In biology, homology is similarity due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologous structures is the forelimbs of vertebrates, where the wings of bats and birds, the arms of primates, the front flippers of whales and the forelegs of four-legged vertebrates like dogs and crocodiles are all derived from the same ancestral tetrapod structure. Evolutionary biology explains homologous structures adapted to different purposes as the result of descent with modification from a common ancestor.
Shotgun sequencingIn genetics, shotgun sequencing is a method used for sequencing random DNA strands. It is named by analogy with the rapidly expanding, quasi-random shot grouping of a shotgun. The chain-termination method of DNA sequencing ("Sanger sequencing") can only be used for short DNA strands of 100 to 1000 base pairs. Due to this size limit, longer sequences are subdivided into smaller fragments that can be sequenced separately, and these sequences are assembled to give the overall sequence.
Green fluorescent proteinThe green fluorescent protein (GFP) is a protein that exhibits bright green fluorescence when exposed to light in the blue to ultraviolet range. The label GFP traditionally refers to the protein first isolated from the jellyfish Aequorea victoria and is sometimes called avGFP. However, GFPs have been found in other organisms including corals, sea anemones, zoanithids, copepods and lancelets. The GFP from A. victoria has a major excitation peak at a wavelength of 395 nm and a minor one at 475 nm.
Gene targetingGene targeting is a biotechnological tool used to change the DNA sequence of an organism (hence it is a form of Genome Editing). It is based on the natural DNA-repair mechanism of Homology Directed Repair (HDR), including Homologous Recombination. Gene targeting can be used to make a range of sizes of DNA edits, from larger DNA edits such as inserting entire new genes into an organism, through to much smaller changes to the existing DNA such as a single base-pair change.
Protein superfamilyA protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if no sequence similarity is evident. Sequence homology can then be deduced even if not apparent (due to low sequence similarity). Superfamilies typically contain several protein families which show sequence similarity within each family.
DNA barcodingDNA barcoding is a method of species identification using a short section of DNA from a specific gene or genes. The premise of DNA barcoding is that by comparison with a reference library of such DNA sections (also called "sequences"), an individual sequence can be used to uniquely identify an organism to species, just as a supermarket scanner uses the familiar black stripes of the UPC barcode to identify an item in its stock against its reference database.
