Molecular Phenotyping

A phenotype results from the expression of an organism’s genes as well as the influence of environmental factors and the interactions between them. A phenotype is the composite of an organism’s discernible characteristics or properties, for instance its biochemical or physiological properties, its development, morphology,  behaviour or phenology. 

Molecular phenotyping describes the technique of quantifying pathway reporter genes. That is, pre-selected genes that are modulated specifically by metabolic and signalling pathways in order to infer activity of these pathways. In most cases molecular phenotyping measures changes of pathway reporter gene expression to characterise modulation of pathway activities induced by disturbances such as stress in a cellular system in vitro. In such context, measurements at early time points are often more informative than later observations because they capture the primary response to the activity by the cellular system. Integrated with quantified changes of phenotype induced by perturbations, molecular phenotyping can identity pathways that contribute to the phenotypic changes. Presently, molecular phenotyping uses RNA sequencing and mRNA expression to infer pathway activities. Recent data suggests that by quantifying pathway reporter gene expression, molecular phenotyping is able to cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes concurrently.  Additionally, molecular phenotyping can be applicable to compounds with a range of binding specificities and is able to sort false positives derived from high content screening tests. Molecular phenotyping allows integration of data derived from in vitro and in vivo models as well as patient data into the drug discovery process within the fields of biotechnology, pharmacology and medicine. 

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