Most current single-cell analysis pipelines are limited to cell embeddings and rely heavily on clustering, while lacking the ability to explicitly model interactions between different feature types. Furthermore, these methods are tailored to specific tasks, as distinct single-cell problems are formulated differently. To address these shortcomings, here we present SIMBA, a graph embedding method that jointly embeds single cells and their defining features, such as genes, chromatin-accessible regions and DNA sequences, into a common latent space. By leveraging the co-embedding of cells and features, SIMBA allows for the study of cellular heterogeneity, clustering-free marker discovery, gene regulation inference, batch effect removal and omics data integration. We show that SIMBA provides a single framework that allows diverse single-cell problems to be formulated in a unified way and thus simplifies the development of new analyses and extension to new single-cell modalities. SIMBA is implemented as a comprehensive Python library ( https://simba-bio.readthedocs.io ).
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http://dx.doi.org/10.1038/s41592-023-01899-8 | DOI Listing |
PLoS Biol
January 2025
Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, Barcelona, Spain.
Fission yeast is an excellent model system that has been widely used to study the mechanism that control cell cycle progression. However, there is a lack of tools that allow to measure with high precision the duration of the different phases of the cell cycle in individual cells. To circumvent this problem, we have developed a fluorescent reporter that allows the quantification of the different phases of the cell cycle at the single-cell level in most genetic backgrounds.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China.
Single-cell sequencing technology provides apparent advantages in cell population heterogeneity, allowing individuals to better comprehend tissues and organs. Sequencing technology is currently moving beyond the standard transcriptome to the single-cell level, which is likely to bring new insights into the function of breast cells. In this study, we examine the primary cell types involved in breast development, as well as achievements in the study of scRNA-seq in the microenvironment, stressing the finding of novel cell subsets using single-cell approaches and analyzing the problems and solutions to scRNA-seq.
View Article and Find Full Text PDFMany agents that show promise in preclinical cancer models lack efficacy in patients due to patient heterogeneity that is not captured in traditional assays. To address this problem, we have developed GENEVA, a platform that measures the molecular and phenotypic consequences of drug perturbations within diverse populations of cancer cells at single-cell resolution, both and . Here, we apply GENEVA to study the KRAS G12C inhibitors, recapitulating known properties of these drugs and uncovering a previously unknown role for mitochondrial activation in cell death induced by KRAS inhibition.
View Article and Find Full Text PDFNat Commun
January 2025
Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Single cell ATAC-seq (scATAC-seq) experimental designs have become increasingly complex, with multiple factors that might affect chromatin accessibility, including genotype, cell type, tissue of origin, sample location, batch, etc., whose compound effects are difficult to test by existing methods. In addition, current scATAC-seq data present statistical difficulties due to their sparsity and variations in individual sequence capture.
View Article and Find Full Text PDFNat Genet
January 2025
Departments of Statistics and Human Genetics, University of Chicago, Chicago, IL, USA.
Profiling tumors with single-cell RNA sequencing has the potential to identify recurrent patterns of transcription variation related to cancer progression, and to produce therapeutically relevant insights. However, strong intertumor heterogeneity can obscure more subtle patterns that are shared across tumors. Here we introduce a statistical method, generalized binary covariance decomposition (GBCD), to address this problem.
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