提出可解释的单细胞数据批效应分析框架,能保留关键生物信号并生成可视化结果。
scMEDAL for the interpretable analysis of single-cell transcriptomics data with batch effect visualization using a deep mixed effects autoencoder
- 用双子网络分别建模批间差异与生物信号,避免信息丢失。
- 在自闭症、白血病等数据上提升疾病状态预测准确率。
- 支持生成反事实表达图,适合研究者理解数据来源影响。
单细胞RNA测序可实现细胞异质性的高分辨率分析,但区分生物信号与批效应仍是重大挑战。现有批校正算法通常抑制或丢弃批相关变异,而非建模。我们提出scMEDAL(单细胞混合效应深度自编码器学习)框架,通过两个互补子网络分别建模批无关与批特异性效应。核心创新scMEDAL-RE为随机效应贝叶斯自编码器,学习批特异性表示,同时保留常被标准校正方法丢失的与批效应共混的生物学意义信息。互补的固定效应子网络scMEDAL-FE通过对抗学习实现默认批校正。在自闭症、白血病、心血管疾病等多种条件、细胞类型及技术与生物效应下评估显示,scMEDAL-RE生成可解释的批特异性嵌入,优于scVI、Scanorama、Harmony、SAUCIE等主流方法,在疾病状态、供体组别和组织类型预测上更准确。scMEDAL还提供生成式可视化,包括细胞在其他批次下的反事实表达重构。该框架可替换固定效应组件,保持scMEDAL-RE的预测能力与可视化优势。总体而言,scMEDAL是一种灵活且可解释的框架,增强对细胞异质性与数据采集过程的理解。
原文摘要 · Abstract (English)
Single-cell RNA sequencing enables high-resolution analysis of cellular heterogeneity, yet disentangling biological signal from batch effects remains a major challenge. Existing batch-correction algorithms suppress or discard batch-related variation rather than modeling it. We propose scMEDAL, single-cell Mixed Effects Deep Autoencoder Learning, a framework that separately models batch-invariant and batch-specific effects using two complementary subnetworks. The principal innovation, scMEDAL-RE, is a random-effects Bayesian autoencoder that learns batch-specific representations while preserving biologically meaningful information confounded with batch effects signal often lost under standard correction. Complementing it, the fixed-effects subnetwork, scMEDAL-FE, trained via adversarial learning provides a default batch-correction component. Evaluations across diverse conditions (autism, leukemia, cardiovascular), cell types, and technical and biological effects show that scMEDAL-RE produces interpretable, batch-specific embeddings that complement both scMEDAL-FE and established correction methods (scVI, Scanorama, Harmony, SAUCIE), yielding more accurate prediction of disease status, donor group, and tissue. scMEDAL also provides generative visualizations, including counterfactual reconstructions of a cell's expression as if acquired in another batch. The framework allows substitution of the fixed-effects component with other correction methods, while retaining scMEDAL-RE's enhanced predictive power and visualization. Overall, scMEDAL is a versatile, interpretable framework that complements existing correction, providing enhanced insight into cellular heterogeneity and data acquisition.
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