3/18/2023 0 Comments Cellprofiler cell intensityWells with colchicine contain significantly fewer cells after 24hr (646☓7) compared to the control wells 4355☒64) p<0.001.īecause the phenotypic approach delivers quantitative data representing a cell’s complete response to specific drugs, researchers are no longer limited to a single specific measurement. This ability to relate changes in the phenotypic profile to a specific drug exposure helps researchers to narrow down the mechanism of action of each drug.Ĭolchicine treated HEK293 cells are phenotypically different from untreated control cells. These data are then used to generate detailed cell profiles which enable researchers to assess a compound’s effect on the entire phenotype. AI-driven software is used to segment these raw images into individual cells and specific cellular components, and extract quantitative measures of cellular features such as size, intensity and texture. Images are then captured using high-content imaging systems. Cells are cultured and treated with the experimental conditions of interest, either via transfection (genetic screening) or compound addition (small molecule), incubated, and then stained with cell paint dyes. The cell painting assay uses up to six fluorescent dyes to label up to eight cellular components and organelles. While the targeted approach to drug discovery is based on existing knowledge of a drug target or a specific hypothesis on its role in disease, the phenotypic profiling approach casts a wider net by capturing all the measurable features related to the cell’s phenotype. 3Įxamples of cells stained with dyes in a Cell Painting assay to detect key cellular components. Since it began work in 2013, Recursion already has four clinical-stage programs and 41 early discovery programs in its pipeline. Their machine learning algorithms enable them to uncover links that would otherwise have remained hidden. 2 Recursion’s workflow-integrating innovations in engineering, laboratory automation, and machine learning-enables it to quantify and processhundreds to thousands of phenotypic features. One example of a lab that is already succeeding with this approach is Recursion, a clinical-stage biotechnology company. High content screening (HCS)-based phenotypic profiling like cell painting is key to advancing drug discovery. It helps researchers identify novel drug candidates or targets that are capable of inducing phenotypes of interest in a more efficient and effective way, slashing the cost and time it takes to develop a drug. Phenotypic profiling is a strategy that uses rich image-based data to quantify cellular profiles, enabling, for example, systemic evaluation of cellular morphologies in response to drug exposure. To help improve their chances of success, the drug discovery community is increasingly embracing phenotypic profiling assays, combined with analysis powered by artificial intelligence (AI). Taking a phenotypic approach to drug discovery The more accurate the predictions on in vivo toxicity and potential adverse reactions, the more is the likelihood of success in clinical trials and getting drugs to market.Īngeline Lim, PhD, applications scientist and bioimaging specialist at Molecular Devices (left) and David Egan, PhD, co-founder and CEO, Core Life Analytics (right) are the authors of this article. When exposed to a drug, unexpected subcellular changes occur in vitro.
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