Deng Kaiwen, Xu Xinya, Zhou Manqi, Li Hongyang, Keller Evan T, Shelley Gregory, Lu Annie, Garmire Lana, Guan Yuanfang
Gilbert S. Omenn Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, MI, USA.
Nat Commun. 2025 Jan 2;16(1):21. doi: 10.1038/s41467-024-55434-0.
Single-cell sequencing provides detailed insights into individual cell behaviors within complex systems based on the assumption that each cell is uniquely isolated. However, doublets-where two or more cells are sequenced together-disrupt this assumption and can lead to potential data misinterpretations. Traditional doublet detection methods primarily rely on simulated genomic data, which may be less effective in homogeneous cell populations and can introduce biases from experimental processes. Therefore, we introduce ImageDoubler in this study, an innovative image-based model that identifies doublets and missing samples leveraging the Fluidigm single-cell sequencing image data. Our approach showcases a notable doublet detection efficacy, achieving a rate up to 93.87% and registering a minimum improvement of 33.1% in F1 scores compared to existing genomic-based methods. This advancement highlights the potential of using imaging to glean insight into developing doublet detection algorithms and exposes the limitations inherent in current genomic-based techniques.
单细胞测序基于每个细胞被独特分离的假设,提供了对复杂系统中单个细胞行为的详细洞察。然而,双联体(即两个或更多细胞一起被测序)破坏了这一假设,并可能导致潜在的数据误解。传统的双联体检测方法主要依赖模拟基因组数据,这在同质细胞群体中可能效果较差,并且可能引入实验过程中的偏差。因此,我们在本研究中引入了ImageDoubler,这是一种创新的基于图像的模型,它利用Fluidigm单细胞测序图像数据识别双联体和缺失样本。我们的方法展示了显著的双联体检测效率,与现有的基于基因组的方法相比,实现了高达93.87%的检出率,F1分数最低提高了33.1%。这一进展凸显了利用成像技术深入了解双联体检测算法的潜力,并揭示了当前基于基因组技术固有的局限性。