An ideal small-molecule screening library would be enriched in non-redundant bioactive compounds that maximize the performance diversity of the library. The construction of such libraries would be aided by a rapid feedback mechanism between synthetic organic chemistry and biology that could indicate during library construction (rather than years later) the transformations and scaffolds that maximize performance diversity. Several groups at the Broad Institute have recently developed assays that annotate small-molecule bioactivity in a rapid, highly multiplexed, and unbiased manner. To assess the suitability of these assays for real-time annotation, cells were treated with a suite of isomeric pyrroles, aziridines, and imines. This dataset reveals that the imaging-based "Cell Painting" assay can 1) distinguish the biological activities of small molecules that are constitutional isomers, and 2) reveal non-obvious trends in those activities.
Images
Images were acquired on an ImageXpress Micro epifluorescent microscope at 20x magnification over 5 fluorescent channels using 6 stains (Cell Painting assay).
BBBC040 dataset
Ground truth
Each assay compound (30 in total) and positive control compound (4 in total) was assayed in quadruplicate at six different assay concentrations. 1,140 cellular features were calculated and assigned to each well/treatment condition.
Please contact Christopher Gerry regarding this dataset.
Published results using this image set
Gerry CJ et al. (2016). Real-Time Biological Annotation of Synthetic Compounds. Journal of the American Chemical Society, 138 (28) pp 8920-8927. doi: 10.1021/jacs.6b04614. PMID: 27398798. PMCID: PMC4976700. (Research article)
