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Advances in spatially-resolved transcriptomics (SRT) technologies have propelled the development of new computational analysis methods to unlock biological insights. As the cost of generating these data decreases, these technologies provide an exciting opportunity to create large-scale atlases that integrate SRT data across multiple tissues, individuals, species, or phenotypes to perform population-level analyses. Here, we describe unique challenges of varying spatial resolutions in SRT data, as well as highlight the opportunities for standardized preprocessing methods along with computational algorithms amenable to atlas-scale datasets leading to improved sensitivity and reproducibility in the future.
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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 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).
View Article and Find Full Text PDFGigascience
January 2025
Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
Background: Pancreatic ductal adenocarcinoma (PDAC), the most common and aggressive form of pancreatic cancer, exhibits profound intratumor morphological heterogeneity, complicating the elucidation of the underlying molecular mechanisms driving its progression.
Results: We present and validate an optimized framework for RNA sequencing (RNA-seq) of multiple spatially resolved laser micro-dissected tumor areas (LMD-seq), along with methodological and analytical details to maximize reproducibility and data mining. This approach enhances sensitivity in detecting lowly expressed genes, outperforming single-cell RNA-seq methods, particularly in identifying rare tumor cell populations and transcriptional programs with low expression.
Small Methods
September 2025
Despite the availability of numerous approved immunotherapies for various cancers, durable progression-free survival remains relatively uncommon among patients with advanced cancer. As research into immunotherapy intensifies, the heterogeneity and complexity of the tumor microenvironment (TME) have emerged as critical determinants of treatment response and a major obstacle to understanding tumor resistance mechanisms. Recent advances in spatially resolved transcriptomics (SRT) enable transcriptome-wide measurement of gene expression while preserving essential spatial information, which supports the characterization of the features of the TME.
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