Unsupervised Deep Embedded Fusion Representation of Single-Cell Transcriptomics

Cell clustering is a critical step in analyzing single-cell RNA sequencing (scRNA-seq) data, which allows us to characterize the cellular heterogeneity of transcriptional profiling at the single-cell level. Single-cell deep embedded representation models have recently become popular since they can learn feature representation and clustering simultaneously. However, the model still suffers from a variety of significant challenges, including the massive amount of data, pervasive dropout events, and complicated noise patterns in transcriptional profiling. Here, we propose a Single-Cell Deep Embedding Fusion Representation (scDEFR) model, which develop a deep embedded fusion representation to learn fused heterogeneous latent embedding that contains both the transcriptome gene-level information and the cell topology information. We first fuse them layer by layer to obtain compressed representations of intercellular relationships and transcriptome information. After that, the zero-inflated negative binomial model (ZINB)-based decoder is proposed to capture the global probabilistic structure of the data and reconstruct the final gene expression information and cell graph. Finally, by simultaneously integrating the clustering loss, crossentropy loss, ZINB loss, and the cell graph reconstruction loss, scDEFR can optimize clustering performance and learn the latent representation in fused information under a joint mutual supervised strategy. We conducted extensive and comprehensive experiments on 15 single-cell RNA-seq datasets from different sequencing platforms to demonstrate the superiority of scDEFR over a variety of state-of-the-art methods.