A multi-use deep learning method for CITE-seq and single-cell RNA-seq data integration with cell surface protein prediction and imputation.

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CITE-seq, a single-cell multi-omics technology that measures RNA and protein expression simultaneously in single cells, has been widely applied in biomedical research, especially in immune related disorders and other diseases such as influenza and COVID-19. Despite the proliferation of CITE-seq, it is still costly to generate such data. Although data integration can increase information content, this raises computational challenges. First, combining multiple datasets is prone to batch effects that need to be addressed. Secondly, it is difficult to combine multiple CITE-seq datasets because the protein panels in different datasets may only partially overlap. Integrating multiple CITE-seq and single-cell RNA-seq (scRNA-seq) datasets is important because this allows the utilization of as many data as possible to uncover cell population heterogeneity. To overcome these challenges, we present sciPENN, a multi-use deep learning approach that supports CITE-seq and scRNA-seq data integration, protein expression prediction for scRNA-seq, protein expression imputation for CITE-seq, quantification of prediction and imputation uncertainty, and cell type label transfer from CITE-seq to scRNA-seq. Comprehensive evaluations spanning multiple datasets demonstrate that sciPENN outperforms other current state-of-the-art methods.