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Abstract The field of spatially resolved transcriptomics (SRT) has greatly advanced our understanding of cellular microenvironments by integrating spatial information with molecular data collected from multiple tissue sections or individuals. However, methods for multi-sample spatial clustering are lacking, and existing methods primarily rely on molecular information alone. This paper introduces BayeSMART, a Bayesian statistical method designed to identify spatial domains across multiple samples. BayeSMART leverages artificial intelligence (AI)-reconstructed single-cell level information from the paired histology images of multi-sample SRT datasets while simultaneously considering the spatial context of gene expression. The AI integration enables BayeSMART to effectively interpret the spatial domains. We conducted case studies using four datasets from various tissue types and SRT platforms, and compared BayeSMART with alternative multi-sample spatial clustering approaches and a number of state-of-the-art methods for single-sample SRT analysis, demonstrating that it surpasses existing methods in terms of clustering accuracy, interpretability, and computational efficiency. BayeSMART offers new insights into the spatial organization of cells in multi-sample SRT data.more » « less
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Abstract Current clustering analysis of spatial transcriptomics data primarily relies on molecular information and fails to fully exploit the morphological features present in histology images, leading to compromised accuracy and interpretability. To overcome these limitations, we have developed a multi-stage statistical method called iIMPACT. It identifies and defines histology-based spatial domains based on AI-reconstructed histology images and spatial context of gene expression measurements, and detects domain-specific differentially expressed genes. Through multiple case studies, we demonstrate iIMPACT outperforms existing methods in accuracy and interpretability and provides insights into the cellular spatial organization and landscape of functional genes within spatial transcriptomics data.more » « less
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Abstract BackgroundRecent developments to segment and characterize the regions of interest (ROI) within medical images have led to promising shape analysis studies. However, the procedures to analyze the ROI are arbitrary and vary by study. A tool to translate the ROI to analyzable shape representations and features is greatly needed. ResultsWe developed SAFARI (shape analysis for AI-segmented images), an open-source package with a user-friendly online tool kit for ROI labelling and shape feature extraction of segmented maps, provided by AI-algorithms or manual segmentation. We demonstrated that half of the shape features extracted by SAFARI were significantly associated with survival outcomes in a case study on 143 consecutive patients with stage I–IV lung cancer and another case study on 61 glioblastoma patients. ConclusionsSAFARI is an efficient and easy-to-use toolkit for segmenting and analyzing ROI in medical images. It can be downloaded from the comprehensive R archive network (CRAN) and accessed athttps://lce.biohpc.swmed.edu/safari/.more » « less
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A recent technology breakthrough in spatial molecular profiling (SMP) has enabled the comprehensive molecular characterizations of single cells while preserving spatial information. It provides new opportunities to delineate how cells from different origins form tissues with distinctive structures and functions. One immediate question in SMP data analysis is to identify genes whose expressions exhibit spatially correlated patterns, called spatially variable (SV) genes. Most current methods to identify SV genes are built upon the geostatistical model with Gaussian process to capture the spatial patterns. However, the Gaussian process models rely on ad hoc kernels that could limit the models' ability to identify complex spatial patterns. In order to overcome this challenge and capture more types of spatial patterns, we introduce a Bayesian approach to identify SV genes via a modified Ising model. The key idea is to use the energy interaction parameter of the Ising model to characterize spatial expression patterns. We use auxiliary variable Markov chain Monte Carlo algorithms to sample from the posterior distribution with an intractable normalizing constant in the model. Simulation studies using both simulated and synthetic data showed that the energy‐based modeling approach led to higher accuracy in detecting SV genes than those kernel‐based methods. When applied to two real spatial transcriptomics (ST) datasets, the proposed method discovered novel spatial patterns that shed light on the biological mechanisms. In summary, the proposed method presents a new perspective for analyzing ST data.more » « less
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