PhenoRipper: software for rapidly profiling microscopy images. A method for high-throughput gene expression signature analysis. Biodiversity of small molecules-a new perspective in screening set selection. A new phenotypic lexicon for accelerated translation: rise of the machines. Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Morphological profiles of RNAi-induced gene knockdown are highly reproducible but dominated by seed effects. Toward performance-diverse small-molecule libraries for cell-based phenotypic screening using multiplexed high-dimensional profiling. Multiplex cytological profiling assay to measure diverse cellular states. A screen for morphological complexity identifies regulators of switch-like transitions between discrete cell shapes. A map of directional genetic interactions in a metazoan cell. A hierarchical map of regulatory genetic interactions in membrane trafficking. Mapping genetic interactions in human cancer cells with RNAi and multiparametric phenotyping. Laufer, C., Fischer, B., Billmann, M., Huber, W. Systems survey of endocytosis by multiparametric image analysis. Clustering phenotype populations by genome-wide RNAi and multiparametric imaging. An approach for extensibly profiling the molecular states of cellular subpopulations. Small molecules discovered in a pathway screen target the Rho pathway in cytokinesis. Integration of chemical and RNAi multiparametric profiles identifies triggers of intracellular mycobacterial killing. Morphobase, an encyclopedic cell morphology database, and its use for drug target identification. Linking phenotypes and modes of action through high-content screen fingerprints. Comparison of methods for image-based profiling of cellular morphological responses to small-molecule treatment. Integrating high-content screening and ligand-target prediction to identify mechanism of action. Image-based multivariate profiling of drug responses from single cells. Compound classification using image-based cellular phenotypes. The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease. Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of mean graph and COMPARE algorithm. Origins of regulated cell-to-cell variability. Cellular heterogeneity: do differences make a difference? Cell 141, 559–563 (2010). Multidimensional drug profiling by automated microscopy. Increasing the content of high-content screening: an overview. The beautiful cell: high-content screening in drug discovery. Integrating phenotypic small-molecule profiling and human genetics: the next phase in drug discovery. Phenotypic screening in cancer drug discovery - past, present and future. The contribution of mechanistic understanding to phenotypic screening for first-in-class medicines. Cell culture and image acquisition takes 2 weeks feature extraction and data analysis take an additional 1–2 weeks. Profiles of cell populations treated with different experimental perturbations can be compared to suit many goals, such as identifying the phenotypic impact of chemical or genetic perturbations, grouping compounds and/or genes into functional pathways, and identifying signatures of disease. Next, an automated image analysis software identifies individual cells and measures ∼1,500 morphological features (various measures of size, shape, texture, intensity, and so on) to produce a rich profile that is suitable for the detection of subtle phenotypes. Cells are plated in multiwell plates, perturbed with the treatments to be tested, stained, fixed, and imaged on a high-throughput microscope. This protocol describes the design and execution of experiments using Cell Painting, which is a morphological profiling assay that multiplexes six fluorescent dyes, imaged in five channels, to reveal eight broadly relevant cellular components or organelles. In morphological profiling, quantitative data are extracted from microscopy images of cells to identify biologically relevant similarities and differences among samples based on these profiles.
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