Abstract

Existing clustering methods for characterizing cell populations from single-cell RNA sequencing are constrained by several limitations stemming from the fact that clusters often cannot be homogeneous, particularly for transitioning populations. On the other hand, dominant cell populations within samples can be identified independently by their strong gene co-expression signatures using methods unrelated to partitioning. Here, we introduce a clustering method, CASCC (co-expression-assisted single-cell clustering), designed to improve biological accuracy using gene co-expression features identified using an unsupervised adaptive attractor algorithm. CASCC outperformed other methods as evidenced by multiple evaluation metrics, and our results suggest that CASCC can improve the analysis of single-cell transcriptomics, enabling potential new discoveries related to underlying biological mechanisms. The CASCC R package is publicly available at https://github.com/LingyiC/CASCC and https://zenodo.org/doi/10.5281/zenodo.10648327.

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