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Norton-Steele, A.

Publications and source records attributed to Norton-Steele, A..

2 recordsLinked to original sources

Development of a universal imaging "phenome" using Shape, Appearance and Motion (SAM) features and the SAM Observation Tool (SPOT)

Cells are plastic, highly heterogeneous and change over time. High-content timelapse imaging promises to reveal dynamic cell behaviors, enabling more accurate identification of cell state and cell fate prediction for biological hypothesis generation and perturbation screens. To empower live-cell imaging based screen, we report the development of 1) a Shape, Appearance, Motion (SAM) "phenome"; a universal set of 2185 image-derived features that act as a image-"transcriptome" to comprehensively quantify an objects instantaneous phenotype; 2) the SAM-Phenotype-Observation-Tool (SPOT), for image-"sequencing" analysis of phenomes. We validated the effectiveness of unbiased SAM-SPOT workflow on publicly available computer vision and 2D single cell imaging datasets. Importantly, we demonstrated that SAM-phenome outperformed features generated by deep learning AI models trained on >1 million fixed single cell and >5000 single cell video frames, respectively. SAM-phenome and SPOT delivers high-throughput, object-treatment-agnostic, comprehensive screening readouts of dynamics, promising to advance novel molecular target discovery and new medicine development.

bioinformatics↗

Identifying phenotype-genotype-function coupling in 3D organoid imaging using Shape, Appearance and Motion Phenotype Observation Tool (SPOT)

Live cells in tissue are plastic, phenotypically dynamic, and modify their function in response to genetic and environmental perturbations. To unleash the power of live-cell imaging to identify phenotype-genotype-function coupling over time, we report the development of a standardized Shape-Appearance-Motion (SAM) "phenome" and SAM-Phenotype-Observation-Tool (SPOT), that act as an image-"transcriptome" and image-"transcriptome analyzer" respectively, and provide unbiased and comprehensive description of morpho-dynamic phenotypes without prior knowledge. We developed and applied SAM-SPOT to our simulated organoids database with known ground-truth and >1.6 million mouse and human organoid instances with defined genetic and chemical perturbations. SAM-SPOT can effectively and robustly characterize 3D morpho-dynamics from 2D projection videos. Combined with single-cell RNA sequencing, SAM-SPOT revealed that altered WNT signaling, but not mutant RAS or p53, predisposes intestinal organoids to irregular morphogenesis. SAM-SPOT advances biomedical discovery by empowering live-cell imaging to identify phenotype-genotype-function relationships through large-scale and cost-effective label-free live-cell imaging.

cancer biology↗