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Integration of the evolving large-scale single-cell transcriptomes requires scalable batch-correction approaches. Here we propose a simple batch-correction method that is scalable for integrating super large-scale single-cell transcriptomes from diverse sources. The core idea of the method is encoding batch information of each cell as a trainable parameter and added to its expression profile; subsequently, a contrastive learning approach is used to learn feature representation of the additive expression profile. We demonstrate the scalability of the proposed method by integrating 18 million cells obtained from the Human Cell Atlas. Our benchmark comparisons with current state-of-the-art single-cell integration methods demonstrated that our method could achieve comparable data alignment and cluster preservation. Our study would facilitate the integration of super large-scale single-cell transcriptomes. The source code is available at https://github.com/xilinshen/Fugue.

Advancement in single-cell RNA sequencing leads to exponential accumulation of single-cell expression data. However, there is still lack of tools that could integrate these unlimited accumulation of single-cell expression data. Here, we presented a universal approach iSEEEK for integrating super large-scale single-cell expression via exploring expression rankings of top-expressing genes. We developed iSEEEK with 13.7 million single-cells. We demonstrated the efficiency of iSEEEK with canonical single-cell downstream tasks on five heterogenous datasets encompassing human and mouse samples. iSEEEK achieved good clustering performance benchmarked against well-annotated cell labels. In addition, iSEEEK could transfer its knowledge learned from large-scale expression data on new dataset that was not involved in its development. iSEEEK enables identification of gene-gene interaction networks that are characteristic of specific cell types. Our study presents a simple and yet effective method to integrate super large-scale single-cell transcriptomes and would facilitate translational single-cell research from bench to bedside.

Summary We developed Miscell, a self-supervised learning approach with deep neural network as latent feature encoder for mining information from single-cell transcriptomes. We demonstrated the capability of Miscell with canonical single-cell analysis tasks including delineation of single-cell clusters and identification of cluster-specific marker genes. We evaluated Miscell along with three state-of-the-art methods on three heterogeneous datasets. Miscell achieved at least comparable or better performance than the other methods by significant margin on a variety of clustering metrics such as adjusted rand index, normalized mutual information, and V-measure score. Miscell can identify cell-type specific markers by quantifying the influence of genes on cell clusters via deep learning approach., Graphical abstract, Highlights • We presented a deep learning approach Miscell to dissecting single-cell transcriptomes • Miscell achieved high performance on canonical single-cell analysis tasks • Miscell can transfer knowledge learned from single-cell transcriptomes to bulk tumors, Biological sciences; Neural networks; Transcriptomics