GLOBE: a contrastive learning-based framework for integrating single-cell transcriptome datasets.

ABSTRACT

Integration of single-cell transcriptome datasets from multiple sources plays an important role in investigating complex biological systems. The key to integration of transcriptome datasets is batch effect removal. Recent methods attempt to apply a contrastive learning strategy to correct batch effects. Despite their encouraging performance, the optimal contrastive learning framework for batch effect removal is still under exploration. We develop an improved contrastive learning-based batch correction framework, GLOBE. GLOBE defines adaptive translation transformations for each cell to guarantee the stability of approximating batch effects. To enhance the consistency of representations alignment, GLOBE utilizes a loss function that is both hardness-aware and consistency-aware to learn batch effect-invariant representations. Moreover, GLOBE computes batch-corrected gene matrix in a transparent approach to support diverse downstream analysis. Benchmarking results on a wide spectrum of datasets show that GLOBE outperforms other state-of-the-art methods in terms of robust batch mixing and superior conservation of biological signals. We further apply GLOBE to integrate two developing mouse neocortex datasets and show GLOBE succeeds in removing batch effects while preserving the contiguous structure of cells in raw data. Finally, a comprehensive study is conducted to validate the effectiveness of GLOBE.