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Spatial transcriptomics enables the simultaneous measurement of morphological features and transcriptional profiles of the same cells or regions in tissues. Here we present multi-modal structured embedding (MUSE), an approach to characterize cells and tissue regions by integrating morphological and spatially resolved transcriptional data. We demonstrate that MUSE can discover tissue subpopulations missed by either modality as well as compensate for modality-specific noise. We apply MUSE to diverse datasets containing spatial transcriptomics (seqFISH+, STARmap or Visium) and imaging (hematoxylin and eosin or fluorescence microscopy) modalities. MUSE identified biologically meaningful tissue subpopulations and stereotyped spatial patterning in healthy brain cortex and intestinal tissues. In diseased tissues, MUSE revealed gene biomarkers for proximity to tumor region and heterogeneity of amyloid precursor protein processing across Alzheimer brain regions. MUSE enables the integration of multi-modal data to provide insights into the states, functions and organization of cells in complex biological tissues.
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http://dx.doi.org/10.1038/s41587-022-01251-z | DOI Listing |
NPJ Precis Oncol
September 2025
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Breast cancer is a highly heterogeneous disease with diverse outcomes, and intra-tumoral heterogeneity plays a significant role in both diagnosis and treatment. Despite its importance, the spatial distribution of intra-tumoral heterogeneity is not fully elucidated. Spatial transcriptomics has emerged as a promising tool to study the molecular mechanisms behind many diseases.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
School of Life Sciences, Anhui Medical University, Hefei, 230032, China; Translational Research Institute of Henan Provincial People's Hospital, Henan International Joint Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial Key Laboratory of Long Non-coding RNA and Cancer Metaboli
Melanoma is the most aggressive and lethal form of skin cancer, posing significant challenges for prognosis assessment and treatment. Recently, metabolic reprogramming and epigenetic regulation have gained attention for their roles in cancer progression. The role of the key metabolic enzyme dihydrolipoic acid succinyltransferase (DLST) in cancer is currently unclear.
View Article and Find Full Text PDFCell Syst
September 2025
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:
Spatial transcriptomics allows for the measurement of gene expression within the native tissue context. However, despite technological advancements, computational methods to link cell states with their microenvironment and compare these relationships across samples and conditions remain limited. To address this, we introduce Tissue Motif-Based Spatial Inference across Conditions (TissueMosaic), a self-supervised convolutional neural network designed to discover and represent tissue architectural motifs from multi-sample spatial transcriptomic datasets.
View Article and Find Full Text PDFPLoS One
September 2025
Institute of Computational Science and Technology, Guangzhou University, Guangzhou, China.
MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology, yet their spatial dynamics within tumor microenvironments (TMEs) remain underexplored due to technical limitations in current spatial transcriptomics (ST) technologies. To address this gap, we present STmiR, a novel XGBoost-based framework for spatially resolved miRNA activity prediction. STmiR integrates bulk RNA-seq data (TCGA and CCLE) with spatial transcriptomics profiles to model nonlinear miRNA-mRNA interactions, achieving high predictive accuracy (Spearman's ρ > 0.
View Article and Find Full Text PDFBioinformatics
September 2025
Department of Mathematical Sciences, The University of Texas at Dallas, TX United States.
Motivation: The advent of next-generation sequencing-based spatially resolved transcriptomics (SRT) techniques has reshaped genomic studies by enabling high-throughput gene expression profiling while preserving spatial and morphological context. Understanding gene functions and interactions in different spatial domains is crucial, as it can enhance our comprehension of biological mechanisms, such as cancer-immune interactions and cell differentiation in various regions. It is necessary to cluster tissue regions into distinct spatial domains and identify discriminating genes that elucidate the clustering result, referred to as spatial domain-specific discriminating genes (DGs).
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