scAMZI: attention-based deep autoencoder with zero-inflated layer for clustering scRNA-seq data.

Abstract

Background: Clustering scRNA-seq data plays a vital role in scRNA-seq data analysis and downstream analyses. Many computational methods have been proposed and achieved remarkable results. However, there are several limitations of these methods. First, they do not fully exploit cellular features. Second, they are developed based on gene expression information and lack of flexibility in integrating intercellular relationships. Finally, the performance of these methods is affected by dropout event.

Results: We propose a novel deep learning (DL) model based on attention autoencoder and zero-inflated (ZI) layer, namely scAMZI, to cluster scRNA-seq data. scAMZI is mainly composed of SimAM (a Simple, parameter-free Attention Module), autoencoder, ZINB (Zero-Inflated Negative Binomial) model and ZI layer. Based on ZINB model, we introduce autoencoder and SimAM to reduce dimensionality of data and learn feature representations of cells and relationships between cells. Meanwhile, ZI layer is used to handle zero values in the data. We compare the performance of scAMZI with nine methods (three shallow learning algorithms and six state-of-the-art DL-based methods) on fourteen benchmark scRNA-seq datasets of various sizes (from hundreds to tens of thousands of cells) with known cell types. Experimental results demonstrate that scAMZI outperforms competing methods.

Conclusions: scAMZI outperforms competing methods and can facilitate downstream analyses such as cell annotation, marker gene discovery, and cell trajectory inference. The package of scAMZI is made freely available at https://doi.org/10.5281/zenodo.13131559 .