论文标题
通过各种因果推断和精致的关系信息来预测细胞反应
Predicting Cellular Responses with Variational Causal Inference and Refined Relational Information
论文作者
论文摘要
预测细胞在扰动下的反应可能会给药物发现和个性化治疗剂带来重要的好处。在这项工作中,我们提出了一个新的图形贝叶斯因果推理框架,以预测细胞的基因表达在反事实扰动下(该细胞未经实际收到的扰动),利用代表生物学知识的信息以基因调节网络(GRN)形式来帮助个性化细胞反应预测。针对数据自适应GRN,我们还开发了用于图形卷积网络的邻接矩阵更新技术,并在预训练期间使用它来完善GRN,这对基因关系和增强模型性能产生了更多见解。此外,我们在框架内提出了一个可靠的估计器,以实现边际扰动效应的渐近有效估计,这在先前的工作中尚待进行。通过广泛的实验,我们表现出与对个体反应预测的最先进的深度学习模型相比,我们的方法的优势。
Predicting the responses of a cell under perturbations may bring important benefits to drug discovery and personalized therapeutics. In this work, we propose a novel graph variational Bayesian causal inference framework to predict a cell's gene expressions under counterfactual perturbations (perturbations that this cell did not factually receive), leveraging information representing biological knowledge in the form of gene regulatory networks (GRNs) to aid individualized cellular response predictions. Aiming at a data-adaptive GRN, we also developed an adjacency matrix updating technique for graph convolutional networks and used it to refine GRNs during pre-training, which generated more insights on gene relations and enhanced model performance. Additionally, we propose a robust estimator within our framework for the asymptotically efficient estimation of marginal perturbation effect, which is yet to be carried out in previous works. With extensive experiments, we exhibited the advantage of our approach over state-of-the-art deep learning models for individual response prediction.