CellContrast: Reconstructing spatial relationships in single-cell RNA sequencing data via deep contrastive learning.

A vast amount of single-cell RNA sequencing (SC) data have been accumulated via various studies and consortiums, but the lack of spatial information limits its analysis of complex biological activities. To bridge this gap, we introduce CellContrast, a computational method for reconstructing spatial relationships among SC cells from spatial transcriptomics (ST) reference. By adopting a contrastive learning framework and training with ST data, CellContrast projects gene expressions into a hidden space where proximate cells share similar representation values. We performed extensive benchmarking on diverse platforms, including SeqFISH, Stereo-seq, 10X Visium, and MERSCOPE, on mouse embryo and human breast cells. The results reveal that CellContrast substantially outperforms other related methods, facilitating accurate spatial reconstruction of SC. We further demonstrate CellContrast's utility by applying it to cell-type co-localization and cell-cell communication analysis with real-world SC samples, proving the recovered cell locations empower more discoveries and mitigate potential false positives.