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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]
For example, in a knock-out screen, one or more genes are completely deleted and the deletion mutants are tested for phenotypes. Such screens have been done for all genes in many bacteria and even complex organisms, such as C. elegans. [1] A reverse genetic screen typically begins with a gene sequence followed by targeted inactivation. [9]
High-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.
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.
Phenotypic screening of chemical libraries is used to identify drug targets (forward genetics or chemoproteomics) or to validate those targets in experimental models of disease (reverse genetics). [2] Recent applications of this topic have been implicated in signal transduction, which may play a role in discovering new cancer treatments. [3]
Chemogenomics Staubli robot retrieves assay plates from incubators. Chemogenomics, or chemical genomics, is the systematic screening of targeted chemical libraries of small molecules against individual drug target families (e.g., GPCRs, nuclear receptors, kinases, proteases, etc.) with the ultimate goal of identification of novel drugs and drug targets. [1]
This can be skipped by obtaining a commercially available library. 2. Screen: Cells are transduced with lentiviral particles containing the sgRNA library, Cas9, and other necessary components. Cells may be transduced in bulk (pooled screen), or in individual wells (arrayed screen). 3: Measurement & Analysis.
A simple screen involves randomly mutating DNA with chemicals or radiation and then selecting those that display the desired trait. For organisms where mutation is not practical, scientists instead look for individuals among the population who present the characteristic through naturally-occurring mutations.