Structure-preserved dimension reduction using joint triplets sampling for multi-batch integration of single-cell transcriptomic data.

Abstract

Dimension reduction (DR) plays an important role in single-cell RNA sequencing (scRNA-seq), such as data interpretation, visualization and other downstream analysis. A desired DR method should be applicable to various application scenarios, including identifying cell types, preserving the inherent structure of data and handling with batch effects. However, most of the existing DR methods fail to accommodate these requirements simultaneously, especially removing batch effects. In this paper, we develop a novel structure-preserved dimension reduction (SPDR) method using intra- and inter-batch triplets sampling. The constructed triplets jointly consider each anchor's mutual nearest neighbors from inter-batch, k-nearest neighbors from intra-batch and randomly selected cells from the whole data, which capture higher order structure information and meanwhile account for batch information of the data. Then we minimize a robust loss function for the chosen triplets to obtain a structure-preserved and batch-corrected low-dimensional representation. Comprehensive evaluations show that SPDR outperforms other competing DR methods, such as INSCT, IVIS, Trimap, Scanorama, scVI and UMAP, in removing batch effects, preserving biological variation, facilitating visualization and improving clustering accuracy. Besides, the two-dimensional (2D) embedding of SPDR presents a clear and authentic expression pattern, and can guide researchers to determine how many cell types should be identified. Furthermore, SPDR is robust to complex data characteristics (such as down-sampling, duplicates and outliers) and varying hyperparameter settings. We believe that SPDR will be a valuable tool for characterizing complex cellular heterogeneity.