The field of high-content screening and analysis consists of a set of methodologies for automated discovery in cell biology and drug development using large amounts of image data. In most cases, imaging is carried out by automated microscopes, often assisted by automated liquid handling and cell culture. Image processing, computer vision, and machine learning are used to automatically process high-dimensional image data into meaningful cell biological results. The key is creating automated analysis pipelines typically consisting of 4 basic steps: (1) image processing (normalization, segmentation, tracing, tracking), (2) spatial transformation to bring images to a common reference frame (registration), (3) computation of image features, and (4) machine learning for modeling and interpretation of data. An overview of these image analysis tools is presented here, along with brief descriptions of a few applications. (Journal of Biomolecular Screening 2010:726-734)

BackgroundDrug discovery and development has been aided by high throughput screening methods that detect compound effects on a single target. However, when using focused initial screening, undesirable secondary effects are often detected late in the development process after significant investment has been made. An alternative approach would be to screen against undesired effects early in the process, but the number of possible secondary targets makes this prohibitively expensive.ResultsThis paper describes methods for making this global approach practical by constructing predictive models for many target responses to many compounds and using them to guide experimentation. We demonstrate for the first time that by jointly modeling targets and compounds using descriptive features and using active machine learning methods, accurate models can be built by doing only a small fraction of possible experiments. The methods were evaluated by computational experiments using a dataset of 177 assays and 20,000 compounds constructed from the PubChem database.ConclusionsAn average of nearly 60% of all hits in the dataset were found after exploring only 3% of the experimental space which suggests that active learning can be used to enable more complete characterization of compound effects than otherwise affordable. The methods described are also likely to find widespread application outside drug discovery, such as for characterizing the effects of a large number of compounds or inhibitory RNAs on a large number of cell or tissue phenotypes.

Supplementary data are available at Bioinformatics online.