PT  - JOURNAL ARTICLE
AU  - Wenkai Han
AU  - Yuqi Cheng
AU  - Jiayang Chen
AU  - Huawen Zhong
AU  - Zhihang Hu
AU  - Siyuan Chen
AU  - Licheng Zong
AU  - Irwin King
AU  - Xin Gao
AU  - Yu Li
TI  - Self-supervised contrastive learning for integrative single cell RNA-seq data analysis
AID  - 10.1101/2021.07.26.453730
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.26.453730
4099  - http://biorxiv.org/content/early/2021/07/27/2021.07.26.453730.short
4100  - http://biorxiv.org/content/early/2021/07/27/2021.07.26.453730.full
AB  - Single-cell RNA-sequencing (scRNA-seq) has become a powerful tool to reveal the complex biological diversity and heterogeneity among cell populations. However, the technical noise and bias of the technology still have negative impacts on the downstream analysis. Here, we present a self-supervised Contrastive LEArning framework for scRNA-seq (CLEAR) profile representation and the downstream analysis. CLEAR overcomes the heterogeneity of the experimental data with a specifically designed representation learning task and thus can handle batch effects and dropout events. In the task, the deep learning model learns to pull together the representations of similar cells while pushing apart distinct cells, without manual labeling. It achieves superior performance on a broad range of fundamental tasks, including clustering, visualization, dropout correction, batch effect removal, and pseudo-time inference. The proposed method successfully identifies and illustrates inflammatory-related mechanisms in a COVID-19 disease study with 43,695 single cells from peripheral blood mononuclear cells. Further experiments to process a million-scale single-cell dataset demonstrate the scalability of CLEAR. This scalable method generates effective scRNA-seq data representation while eliminating technical noise, and it will serve as a general computational framework for single-cell data analysis.Competing Interest StatementThe authors have declared no competing interest.