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Phenotypic 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. [1]
A genetic screen or mutagenesis screen is an experimental technique used to identify and select individuals who possess a phenotype of interest in a mutagenized population. [1] Hence a genetic screen is a type of phenotypic screen .
Given the increase in the use of phenotypic/visual screening as a cell biological tool, methods are required that permit systematic biochemical target identification if these molecules are to be of broad use. [6] Target identification has been defined as the rate limiting step in chemical genetics/high-content screening. [7]
In this context, a phenotypic screen is usually employed to identify drugs with a desired effect in vitro, such as inhibition of viral plaque formation. If a drug produces a positive test, the next step is to determine whether it is acting on a known or novel target. Chemoproteomics is thus a follow-up to phenotypic screening.
Over recent years, the genome-wide CRISPR screen has emerged as a powerful tool for performing large-scale loss-of-function screens, with low noise, high knockout efficiency and minimal off-target effects. Genome-wide CRISPR/Cas9 Knockout Screens: Workflow Overview. 1.
More recently, large-scale phenotypic screens have also been used in animals, e.g. to study lesser understood phenotypes such as behavior. In one screen, the role of mutations in mice were studied in areas such as learning and memory, circadian rhythmicity, vision, responses to stress and response to psychostimulants.
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Forward genetics is a molecular genetics approach of determining the genetic basis responsible for a phenotype. Forward genetics provides an unbiased approach because it relies heavily on identifying the genes or genetic factors that cause a particular phenotype or trait of interest.