Learning discriminative and structural samples for rare cell types with deep generative model.

Cell types (subpopulations) serve as bio-markers for the diagnosis and therapy of complex diseases, and single-cell RNA-sequencing (scRNA-seq) measures expression of genes at cell level, paving the way for the identification of cell types. Although great efforts have been devoted to this issue, it remains challenging to identify rare cell types in scRNA-seq data because of the few-shot problem, lack of interpretability and separation of generating samples and clustering of cells. To attack these issues, a novel deep generative model for leveraging the small samples of cells (aka scLDS2) is proposed by precisely estimating the distribution of different cells, which discriminate the rare and non-rare cell types with adversarial learning. Specifically, to enhance interpretability of samples, scLDS2 generates the sparse faked samples of cells with $\ell _1$-norm, where the relations among cells are learned, facilitating the identification of cell types. Furthermore, scLDS2 directly obtains cell types from the generated samples by learning the block structure such that cells belonging to the same types are similar to each other with the nuclear-norm. scLDS2 joins the generation of samples, classification of the generated and truth samples for cells and feature extraction into a unified generative framework, which transforms the rare cell types detection problem into a classification problem, paving the way for the identification of cell types with joint learning. The experimental results on 20 datasets demonstrate that scLDS2 significantly outperforms 17 state-of-the-art methods in terms of various measurements with 25.12% improvement in adjusted rand index on average, providing an effective strategy for scRNA-seq data with rare cell types. (The software is coded using python, and is freely available for academic https://github.com/xkmaxidian/scLDS2).