数据集不平衡对单细胞数据整合的影响，这一成果由加拿大大学健康网络Bo Wang、Hassaan Maan和多伦多大学Kieran R. Campbell研究组合作取得。该研究于2024年3月1日发表于国际学术期刊《自然-生物技术》杂志。

在这项研究中，研究人员检测了不同样本中存在的细胞类型、每种细胞类型的细胞数和细胞类型比例差异，如何影响数据整合后的下游分析。Iniquitate方法评估了数据集之间不平衡扰动后整合结果的稳健性。在2,600次整合实验中，对五种最先进单细胞RNA测序整合技术进行的基准测试表明，样本不平衡对下游分析和整合结果的生物学解释有重大影响。

不平衡扰动可导致无监督聚类、细胞类型分类、差异表达和标记基因注释、查询-参考映射和轨迹推断出现统计学上的显著差异。研究人员通过新引入的属性-聚合细胞类型支持和最小细胞类型中心距，量化了不平衡的影响。为了更好地描述和减弱不平衡的影响，该研究为整合方法用户引入了平衡聚类指标和不平衡整合指南。

据悉，整合多个样本和不同条件产生的单细胞转录组数据的计算方法，通常不会考虑不同数据集所测量细胞类型的不平衡性。

附：英文原文

Title: Characterizing the impacts of dataset imbalance on single-cell data integration

Author: Maan, Hassaan, Zhang, Lin, Yu, Chengxin, Geuenich, Michael J., Campbell, Kieran R., Wang, Bo

Issue&Volume: 2024-03-01

Abstract: Computational methods for integrating single-cell transcriptomic data from multiple samples and conditions do not generally account for imbalances in the cell types measured in different datasets. In this study, we examined how differences in the cell types present, the number of cells per cell type and the cell type proportions across samples affect downstream analyses after integration. The Iniquitate pipeline assesses the robustness of integration results after perturbing the degree of imbalance between datasets. Benchmarking of five state-of-the-art single-cell RNA sequencing integration techniques in 2,600 integration experiments indicates that sample imbalance has substantial impacts on downstream analyses and the biological interpretation of integration results. Imbalance perturbation led to statistically significant variation in unsupervised clustering, cell type classification, differential expression and marker gene annotation, query-to-reference mapping and trajectory inference. We quantified the impacts of imbalance through newly introduced properties—aggregate cell type support and minimum cell type center distance. To better characterize and mitigate impacts of imbalance, we introduce balanced clustering metrics and imbalanced integration guidelines for integration method users.

DOI: 10.1038/s41587-023-02097-9

Source: https://www.nature.com/articles/s41587-023-02097-9