Cell segmentation-free inference of cell types from in situ transcriptomics data
Lars E. Borm,
Thuc Nghi Nguyen,
Posted 13 Oct 2019
bioRxiv DOI: 10.1101/800748
Posted 13 Oct 2019
Multiplexed fluorescence in situ hybridization techniques have enabled cell-type identification, linking transcriptional heterogeneity with spatial heterogeneity of cells. However, inaccurate cell segmentation reduces the efficacy of cell-type identification and tissue characterization. Here, we present a novel method called Spot-based Spatial cell-type Analysis by Multidimensional mRNA density estimation (SSAM), a robust cell segmentation-free computational framework for identifying cell-types and tissue domains in 2D and 3D. SSAM is applicable to a variety of in situ transcriptomics techniques and capable of integrating prior knowledge of cell types. We apply SSAM to three mouse brain tissue images: the somatosensory cortex imaged by osmFISH, the hypothalamic preoptic region by MERFISH, and the visual cortex by multiplexed smFISH. We found that SSAM detects regions occupied by known cell types that were previously missed and discovers new cell types.
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