Joint representation and visualization of derailed cell states with Decipher.

Achille Nazaret, Joy Linyue Fan, Vincent-Philippe Lavallée, Cassandra Burdziak, Andrew E Cornish, Vaidotas Kiseliovas, Robert L Bowman, Ignas Masilionis, Jaeyoung Chun, Shira E Eisman, James Wang, Justin Hong, Lingting Shi, Ross L Levine, Linas Mazutis, David Blei, Dana Pe'er, Elham Azizi
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Abstract

Biological insights often depend on comparing conditions such as disease and health, yet we lack effective computational tools for integrating single-cell genomics data across conditions or characterizing transitions from normal to deviant cell states. Here, we present Decipher, a deep generative model that characterizes derailed cell-state trajectories. Decipher jointly models and visualizes gene expression and cell state from normal and perturbed single-cell RNA-seq data, revealing shared and disrupted dynamics. We demonstrate its superior performance across diverse contexts, including in pancreatitis with oncogene mutation, acute myeloid leukemia, and gastric cancer.

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深度生成模型解读急性髓性白血病的脱轨轨迹。
单细胞基因组学有可能以一种无偏倚的方式绘制细胞状态及其动态,以响应疾病等扰动。然而,阐明细胞状态从健康到疾病的转变需要分析来自扰动样本和未扰动参考样本的数据。现有的整合和联合可视化来自不同背景的单细胞数据集的方法往往会消除关键的生物学差异,或者不能正确地协调共享机制。我们提出了Decipher模型,该模型结合了变分自编码器和深度指数族来重建脱轨轨迹(https://github.com/azizilab/decipher)。破译联合代表正常和受干扰的单细胞RNA-seq数据集,揭示共享和破坏的动态。它进一步引入了一种新的方法来可视化数据,而不需要UMAP或TSNE等方法。我们在急性髓性白血病患者骨髓标本的数据上展示了Decipher,表明它成功地表征了与正常造血的差异,并识别了当每个患者获得NPM1驱动突变时被破坏的转录程序。
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