Smithy, J. W. | Search bioRxiv

bioRxiv2024

Decoding Spatial Tissue Architecture: A Scalable Bayesian Topic Model for Multiplexed Imaging Analysis

Recent progress in multiplexed tissue imaging is advancing the study of tumor microenvironments to enhance our understanding of treatment response and disease progression. Cellular neighborhood analysis is a popular computational approach for these complex image data. Despite its popularity, there are significant challenges, including high computational demands that limit feasibility for largescale applications and the lack of a principled strategy for integrative analysis across images. This absence hampers the precise and consistent identification of spatial features and tracking of their dynamics over disease progression. To overcome these challenges, we introduce SpatialTopic, a spatial topic model designed to decode high-level spatial architecture across multiplexed tissue images. SpatialTopic integrates both cell type and spatial information within a topic modelling framework, originally developed for natural language processing and adapted for computer vision. Spatial information is incorporated into the flexible design of documents, representing densely overlapping regions in images. We employ an efficient collapsed Gibbs sampling algorithm for model inference. We benchmarked the performance against five state-of-the-art algorithms through various case studies using different single-cell spatial transcriptomic and proteomic imaging platforms across different tissue types. We show that SpatialTopic is highly scalable on large-scale image datasets with millions of cells, along with high precision and interpretability. Our findings demonstrate that SpatialTopic consistently identifies biologically and clinically significant spatial "topics" such as tertiary lymphoid structures (TLSs) and tracks dynamic changes in spatial features over disease progression. Its computational efficiency and broad applicability across various molecular imaging platforms will enhance the analysis of large-scale tissue imaging datasets.

bioinformatics↗

bioRxiv2024

Spatial Immunophenotyping from Whole-Slide Multiplexed Tissue Imaging Using Convolutional Neural Networks

The multiplexed immunofluorescence (mIF) platform enables biomarker discovery through the simultaneous detection of multiple markers on a single tissue slide, offering detailed insights into intratumor heterogeneity and the tumor-immune microenvironment at spatially resolved single cell resolution. However, current mIF image analyses are labor-intensive, requiring specialized pathology expertise which limits their scalability and clinical application. To address this challenge, we developed CellGate, a deep-learning (DL) computational pipeline that provides streamlined, end-to-end whole-slide mIF image analysis including nuclei detection, cell segmentation, cell classification, and combined immuno-phenotyping across stacked images. The model was trained on over 750,000 single cell images from 34 melanomas in a retrospective cohort of patients using whole tissue sections stained for CD3, CD8, CD68, CK-SOX10, PD-1, PD-L1, and FOXP3 with manual gating and extensive pathology review. When tested on new whole mIF slides, the model demonstrated high precision-recall AUC. Further validation on whole-slide mIF images of 9 primary melanomas from an independent cohort confirmed that CellGate can reproduce expert pathology analysis with high accuracy. We show that spatial immuno-phenotyping results using CellGate provide deep insights into the immune cell topography and differences in T cell functional states and interactions with tumor cells in patients with distinct histopathology and clinical characteristics. This pipeline offers a fully automated and parallelizable computing process with substantially improved consistency for cell type classification across images, potentially enabling high throughput whole-slide mIF tissue image analysis for large-scale clinical and research applications.

bioinformatics↗