scDTL: enhancing single-cell RNA-seq imputation through deep transfer learning with bulk cell information.

The increasing single-cell RNA sequencing (scRNA-seq) data enable researchers to explore cellular heterogeneity and gene expression profiles, offering a high-resolution view of the transcriptome at the single-cell level. However, the dropout events, which are often present in scRNA-seq data, remaining challenges for downstream analysis. Although a number of studies have been developed to recover single-cell expression profiles, their performance may be hindered due to not fully exploring the inherent relations between genes. To address the issue, we propose scDTL, a deep transfer learning based approach for scRNA-seq data imputation by harnessing the bulk RNA-sequencing information. We firstly employ a denoising autoencoder trained on bulk RNA-seq data as the initial imputation model, and then leverage a domain adaptation framework that transfers the knowledge learned by the bulk imputation model to scRNA-seq learning task. In addition, scDTL employs a parallel operation with a 1D U-Net denoising model to provide gene representations of varying granularity, capturing both coarse and fine features of the scRNA-seq data. Finally, we utilize a cross-channel attention mechanism to fuse the features learned from the transferred bulk imputation model and U-Net model. In the evaluation, we conduct extensive experiments to demonstrate that scDTL could outperform other state-of-the-art methods in the quantitative comparison and downstream analyses.