scRNA-seq Data Clustering by Cluster-aware Iterative Contrastive Learning

Single-cell RNA sequencing (scRNA-seq) enables researchers to analyze gene expression at single-cell level. One important task in scRNA-seq data analysis is unsupervised clustering, which helps identify distinct cell types, laying down the foundation for other downstream analysis tasks. In this paper, we propose a novel method called Cluster-aware Iterative Contrastive Learning (CICL in short) for scRNA-seq data clustering, which utilizes an iterative representation learning and clustering framework to progressively learn the clustering structure of scRNA-seq data with a cluster-aware contrastive loss. CICL consists of a Transformer encoder, a clustering head, a projection head and a contrastive loss module. First, CICL extracts the feature vectors of the original and augmented data by the Transformer encoder. Then, it computes the clustering centroids by K-means and employs the student t-distribution to assign pseudo-labels to all cells in the clustering head. The projection-head uses a Multi-Layer Perceptron (MLP) to obtain projections of the augmented data. At last, both pseudo-labels and projections are used in the contrastive loss to guide the model training. Such a process goes iteratively so that the clustering result becomes better and better. Extensive experiments on 25 real world scRNA-seq datasets show that CICL outperforms the SOTA methods. Concretely, CICL surpasses the existing methods by from 14% to 280%, and from 5% to 133% on average in terms of performance metrics ARI and NMI respectively.