Elucidating tumor heterogeneity from spatially resolved transcriptomics data by multi-view graph collaborative learning

利用多视图图协同学习从空间分辨转录组学数据阐明肿瘤异质性

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Abstract

Spatially resolved transcriptomics (SRT) technology enables us to gain novel insights into tissue architecture and cell development, especially in tumors. However, lacking computational exploitation of biological contexts and multi-view features severely hinders the elucidation of tissue heterogeneity. Here, we propose stMVC, a multi-view graph collaborative-learning model that integrates histology, gene expression, spatial location, and biological contexts in analyzing SRT data by attention. Specifically, stMVC adopting semi-supervised graph attention autoencoder separately learns view-specific representations of histological-similarity-graph or spatial-location-graph, and then simultaneously integrates two-view graphs for robust representations through attention under semi-supervision of biological contexts. stMVC outperforms other tools in detecting tissue structure, inferring trajectory relationships, and denoising on benchmark slices of human cortex. Particularly, stMVC identifies disease-related cell-states and their transition cell-states in breast cancer study, which are further validated by the functional and survival analysis of independent clinical data. Those results demonstrate clinical and prognostic applications from SRT data.

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