arXiv:2508.18304q-bio.GNcs.AI2025-08

通过对比学习融合单细胞多组学数据,提升细胞表征精度。

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

  • 引入组内与组间对比学习,整合多组学互补信息。
  • 在4个数据集上超越8种主流方法,精准识别3类单核细胞亚群。
  • 唯一能正确构建造血干细胞到记忆B细胞的发育轨迹,适合生物机制研究。

单细胞多组学数据蕴含丰富的细胞状态信息,分析这些数据有助于揭示细胞异质性、疾病机制和生物过程。然而,由于细胞分化与发育是连续动态过程,基于单细胞多组学数据计算建模并推断细胞互作模式仍具挑战。本文提出scI2CL,一种基于组内与组间对比学习的单细胞多组学融合框架,旨在从互补的多组学数据中学习全面且具有判别性的细胞表征,支持多种下游任务。在四个下游任务的大量实验验证中,scI2CL表现优异,优于现有主流方法。具体而言,在细胞聚类任务中,scI2CL在四个常用真实数据集上超越八种先进方法;在细胞亚型识别中,成功区分出三种未被现有方法发现的潜在单核细胞亚群;同时,scI2CL是唯一能准确重建从造血干细胞及祖细胞到记忆B细胞的细胞发育轨迹的方法;此外,它还解决了两类CD4+ T细胞亚群之间的细胞类型误分类问题,而现有方法无法精确区分混合细胞。综上,scI2CL能准确刻画细胞间的跨组学关系,有效融合多组学数据,学习判别性细胞表征,支持多样化的下游分析任务。

原文摘要 · Abstract (English)

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.

单细胞多组学对比学习细胞谱系

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