Li Ruiqi, Qu Rihao, Parisi Fabio, Strino Francesco, Lam Hainan, Stanley Jay S, Cheng Xiuyuan, Myung Peggy, Kluger Yuval
Computational Biology & Biomedical Informatics Program, Yale University, New Haven, CT, USA.
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Commun Biol. 2025 Jul 16;8(1):1058. doi: 10.1038/s42003-025-08485-y.
Identifying accurate cell markers in single-cell RNA-seq data is crucial for understanding cellular diversity and function. Localized Marker Detector (LMD) is a novel tool to identify "localized genes"-genes exclusively expressed in groups of highly similar cells-thereby characterizing cellular diversity in a multi-resolution and fine-grained manner. LMD constructs a cell-cell affinity graph, diffuses the gene expression value across the cell graph, and assigns a score to each gene based on its diffusion dynamics. LMD's candidate markers can be grouped into functional gene modules, which accurately reflect cell types, subtypes, and other sources of variation such as cell cycle status. We apply LMD to mouse bone marrow and hair follicle dermal condensate datasets, where it facilitates cross-sample comparisons by identifying shared and sample-specific gene signatures and novel cell populations, without requiring batch effect correction or integration. We also assess the performance of LMD across ten single-cell RNA sequencing datasets, compare it to eight existing methods with similar objectives, and find that LMD outperforms the other methods evaluated.
在单细胞RNA测序数据中识别准确的细胞标志物对于理解细胞多样性和功能至关重要。局部标志物检测器(LMD)是一种新型工具,用于识别“局部基因”——即在高度相似的细胞群体中特异性表达的基因——从而以多分辨率和细粒度的方式表征细胞多样性。LMD构建细胞-细胞亲和图,在细胞图上扩散基因表达值,并根据其扩散动力学为每个基因分配一个分数。LMD的候选标志物可以分组为功能基因模块,这些模块准确反映细胞类型、亚型以及其他变异来源,如细胞周期状态。我们将LMD应用于小鼠骨髓和毛囊真皮凝聚物数据集,通过识别共享的和样本特异性的基因特征以及新的细胞群体,LMD有助于跨样本比较,而无需批次效应校正或整合。我们还在十个单细胞RNA测序数据集上评估了LMD的性能,将其与八个具有类似目标的现有方法进行比较,发现LMD优于其他评估方法。
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