Park Cameron, Mani Shouvik, Beltran-Velez Nicolas, Maurer Katie, Gohil Satyen, Li Shuqiang, Huang Teddy, Knowles David A, Wu Catherine J, Azizi Elham
Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
Irving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA.
bioRxiv. 2023 Nov 16:2023.11.14.566956. doi: 10.1101/2023.11.14.566956.
Characterizing cell-cell communication and tracking its variability over time is essential for understanding the coordination of biological processes mediating normal development, progression of disease, or responses to perturbations such as therapies. Existing tools lack the ability to capture time-dependent intercellular interactions, such as those influenced by therapy, and primarily rely on existing databases compiled from limited contexts. We present DIISCO, a Bayesian framework for characterizing the temporal dynamics of cellular interactions using single-cell RNA-sequencing data from multiple time points. Our method uses structured Gaussian process regression to unveil time-resolved interactions among diverse cell types according to their co-evolution and incorporates prior knowledge of receptor-ligand complexes. We show the interpretability of DIISCO in simulated data and new data collected from CAR-T cells co-cultured with lymphoma cells, demonstrating its potential to uncover dynamic cell-cell crosstalk.
表征细胞间通讯并追踪其随时间的变化对于理解介导正常发育、疾病进展或对诸如治疗等扰动的反应的生物过程的协调至关重要。现有工具缺乏捕捉时间依赖性细胞间相互作用的能力,例如受治疗影响的相互作用,并且主要依赖于从有限背景编译的现有数据库。我们提出了DIISCO,这是一个贝叶斯框架,用于使用来自多个时间点的单细胞RNA测序数据来表征细胞相互作用的时间动态。我们的方法使用结构化高斯过程回归,根据不同细胞类型的共同进化揭示它们之间的时间分辨相互作用,并纳入受体-配体复合物的先验知识。我们展示了DIISCO在模拟数据和从与淋巴瘤细胞共培养的CAR-T细胞收集的新数据中的可解释性,证明了其揭示动态细胞间串扰的潜力。