CCST: Cell clustering for spatial transcriptomics data with graph neural network

Abstract Spatial transcriptomics data can provide high-throughput gene expression profiling and spatial structure of tissues simultaneously. An essential question of its initial analysis is cell clustering. However, most existing studies rely on only gene expression information and cannot utilize spatial information efficiently. Taking advantages of two recent technical development, spatial transcriptomics and graph neural network, we thus introduce CCST, C ell C lustering for S patial T ranscriptomics data with graph neural network, an unsupervised cell clustering method based on graph convolutional network to improve ab initio cell clustering and discovering of novel sub cell types based on curated cell category annotation. CCST is a general framework for dealing with various kinds of spatially resolved transcriptomics. With application to five in vitro and in vivo spatial datasets, we show that CCST outperforms other spatial cluster approaches on spatial transcriptomics datasets, and can clearly identify all four cell cycle phases from MERFISH data of cultured cells, and find novel functional sub cell types with different micro-environments from seqFISH+ data of brain, which are all validated experimentally, inspiring novel biological hypotheses about the underlying interactions among cell state, cell type and micro-environment.