Tejada-Lapuerta Alejandro, Bertin Paul, Bauer Stefan, Aliee Hananeh, Bengio Yoshua, Theis Fabian J
Institute of Computational Biology, Helmholtz Munich, Munich, Germany.
School of Computing, Information and Technology, Technical University of Munich, Munich, Germany.
Nat Genet. 2025 Apr;57(4):797-808. doi: 10.1038/s41588-025-02124-2. Epub 2025 Mar 31.
Advances in single-cell '-omics' allow unprecedented insights into the transcriptional profiles of individual cells and, when combined with large-scale perturbation screens, enable measuring of the effect of targeted perturbations on the whole transcriptome. These advances provide an opportunity to better understand the causative role of genes in complex biological processes. In this Perspective, we delineate the application of causal machine learning to single-cell genomics and its associated challenges. We first present the causal model that is most commonly applied to single-cell biology and then identify and discuss potential approaches to three open problems: the lack of generalization of models to novel experimental conditions, the complexity of interpreting learned models, and the difficulty of learning cell dynamics.
单细胞“组学”技术的进步使人们能够以前所未有的方式洞察单个细胞的转录谱,并且当与大规模扰动筛选相结合时,能够测量靶向扰动对整个转录组的影响。这些进展为更好地理解基因在复杂生物学过程中的因果作用提供了机会。在这篇观点文章中,我们阐述了因果机器学习在单细胞基因组学中的应用及其相关挑战。我们首先介绍最常用于单细胞生物学的因果模型,然后识别并讨论针对三个开放性问题的潜在方法:模型对新实验条件缺乏通用性、解释所学模型的复杂性以及学习细胞动态的困难。