scI2CL: Effectively Integrating Single-cell Multi-omics by Intra- and Inter-omics Contrastive Learning

TL;DR

scI2CL is a novel contrastive learning framework that effectively integrates single-cell multi-omics data, enabling improved cellular analysis such as clustering, subtyping, and trajectory inference, surpassing existing methods.

Contribution

The paper introduces scI2CL, a new contrastive learning-based method for multi-omics data fusion that enhances cellular representation learning and downstream analysis accuracy.

Findings

Outperforms eight state-of-the-art methods in cell clustering.

Successfully distinguishes latent monocyte subpopulations.

Accurately reconstructs cell developmental trajectories.

Abstract

Single-cell multi-omics data contain huge information of cellular states, and analyzing these data can reveal valuable insights into cellular heterogeneity, diseases, and biological processes. However, as cell differentiation \& development is a continuous and dynamic process, it remains challenging to computationally model and infer cell interaction patterns based on single-cell multi-omics data. This paper presents scI2CL, a new single-cell multi-omics fusion framework based on intra- and inter-omics contrastive learning, to learn comprehensive and discriminative cellular representations from complementary multi-omics data for various downstream tasks. Extensive experiments of four downstream tasks validate the effectiveness of scI2CL and its superiority over existing peers. Concretely, in cell clustering, scI2CL surpasses eight state-of-the-art methods on four widely-used real-world datasets. In cell subtyping, scI2CL effectively distinguishes three latent monocyte cell subpopulations, which are not discovered by existing methods. Simultaneously, scI2CL is the only method that correctly constructs the cell developmental trajectory from hematopoietic stem and progenitor cells to Memory B cells. In addition, scI2CL resolves the misclassification of cell types between two subpopulations of CD4+ T cells, while existing methods fail to precisely distinguish the mixed cells. In summary, scI2CL can accurately characterize cross-omics relationships among cells, thus effectively fuses multi-omics data and learns discriminative cellular representations to support various downstream analysis tasks.