A5090361492- Cell Image Analysis Techniques
- Image Processing Techniques and Applications
- Single-cell and spatial transcriptomics
- Advanced Fluorescence Microscopy Techniques
- Neuroscience and Neural Engineering
- Metabolomics and Mass Spectrometry Studies
- Adipose Tissue and Metabolism
- Genomics and Rare Diseases
- Pluripotent Stem Cells Research
- Biomedical Text Mining and Ontologies
- Lipid metabolism and biosynthesis
- 3D Printing in Biomedical Research
- Genomics and Phylogenetic Studies
- Digital Imaging for Blood Diseases
- Peroxisome Proliferator-Activated Receptors
- Genetic Associations and Epidemiology
- CRISPR and Genetic Engineering
- Genomic variations and chromosomal abnormalities
Broad Institute
2019-2025
Abstract The identification of genetic and chemical perturbations with similar impacts on cell morphology can elucidate compounds’ mechanisms action or novel regulators pathways. Research methods for identifying such similarities has lagged due to a lack carefully designed well-annotated image sets cells treated perturbations. Here we create Resource dataset, CPJUMP1, in which each perturbed gene’s product is known target at least two compounds the dataset. We systematically explore...
Abstract Identifying genetic and chemical perturbations with similar impacts on cell morphology can reveal compounds’ mechanisms of action or novel regulators pathways. Research methods for identifying such similarities has lagged due to a lack carefully designed well-annotated image sets cells treated perturbations. Here, we create Resource dataset, CPJUMP1, where each perturbed gene is known target at least two compounds in the dataset. We systematically explore directionality correlations...
Cellular exposure to free fatty acids (FFAs) is implicated in the pathogenesis of obesity-associated diseases. However, there are no scalable approaches comprehensively assess diverse FFAs circulating human plasma. Furthermore, assessing how FFA-mediated processes interact with genetic risk for disease remains elusive. Here, we report design and implementation acid library comprehensive ontologies (FALCON), an unbiased, scalable, multimodal interrogation 61 structurally FFAs. We identified a...
Abstract In image-based profiling, software extracts thousands of morphological features cells from multi-channel fluorescence microscopy images, yielding single-cell profiles that can be used for basic research and drug discovery. Powerful applications have been proven, including clustering chemical genetic perturbations based on their similar impact, identifying disease phenotypes by observing differences in between healthy diseased cells, predicting assay outcomes using machine learning,...
Quantitative microscopy is a powerful method for performing phenotypic screens from which image-based profiling can extract wealth of information, termed profiles. These profiles be used to elucidate the changes in cellular phenotypes across cell populations different patient samples or following genetic chemical perturbations. One such Cell Painting assay, provides morphological insight through imaging eight compartments. Here, we examine performance assay multiple high-throughput...
Abstract Single-cell resolution technologies warrant computational methods that capture cell heterogeneity while allowing efficient comparisons of populations. Here, we summarize populations by adding features’ dispersion and covariances to population averages, in the context image-based profiling. We find data fusion is critical for these metrics improve results over prior alternatives, providing at least ~20% better performance predicting a compound’s mechanism action (MoA) gene’s pathway.
Advances in high-throughput microscopy have enabled the rapid acquisition of large numbers high-content images. Whether by deep learning or classical algorithms, image analysis pipelines then produce single-cell features. To process these single-cells for downstream applications, we present Pycytominer, a user-friendly, open-source python package that implements bioinformatics steps, known as image-based profiling. We demonstrate Pycytominers usefulness machine project to predict nuisance...
Abstract Human induced pluripotent stem cell-derived (iPSC) neural cultures offer clinically relevant models of human diseases, including Amyotrophic Lateral Sclerosis, Alzheimer’s, and Autism Spectrum Disorder. In situ characterization the spatial-temporal evolution cell state in 3D culture subsequent 2D dissociated based on protein expression levels localizations is essential to understanding differentiation, disease phenotypes, sample-to-sample variability. Here, we apply PR obe-based I...
Widespread sequencing has yielded thousands of missense variants predicted or confirmed as disease-causing. This creates a new bottleneck: determining the functional impact each variant - largely painstaking, customized process undertaken one few genes at time. Here, we established high-throughput imaging platform to assay coding variation on protein localization, evaluating 3,547 over 1,000 and phenotypes. We discovered that mislocalization is common consequence variation, affecting about...
Quantitative microscopy is a powerful method for performing phenotypic screens from which image-based profiling can extract wealth of information, termed profiles. These profiles be used to elucidate the changes in cellular phenotypes across cell populations different patient samples or following genetic chemical perturbations. One such Cell Painting assay, provides morphological insight through imaging eight compartments. Here, we examine performance assay multiple high-throughput...
Cellular exposure to free fatty acids (FFA) is implicated in the pathogenesis of obesity-associated diseases. However, studies date have assumed that a few select FFAs are representative broad structural categories, and there no scalable approaches comprehensively assess biological processes induced by diverse circulating human plasma. Furthermore, assessing how these FFA- mediated interact with genetic risk for disease remains elusive. Here we report design implementation FALCON (Fatty Acid...
Abstract Human induced pluripotent stem cell-derived (iPSC) neural cultures offer clinically relevant models of human diseases, including Amyotrophic Lateral Sclerosis, Alzheimer’s, and Autism Spectrum Disorder. In situ characterization the spatial-temporal evolution cell state in 2D 3D culture organoids based on protein expression levels localizations is essential to understanding differentiation, disease phenotypes, sample-to-sample variability. Here we apply PRobe-based Imaging for...