Deep generative models in single-cell omics

Abstract

Deep Generative Models (DGMs) are becoming instrumental for inferring probability distributions inherent to complex processes, such as most questions in biomedical research. For many years, there was a lack of mathematical methods that would allow this inference in the scarce data scenario of biomedical research. The advent of single-cell omics has finally made square the so-called "skinny matrix", allowing to apply mathematical methods already extensively used in other areas. Moreover, it is now possible to integrate data at different molecular levels in thousands or even millions of samples, thanks to the number of single-cell atlases being collaboratively generated. Additionally, DGMs have proven useful in other frequent tasks in single-cell analysis pipelines, from dimensionality reduction, cell type annotation to RNA velocity inference. In spite of its promise, DGMs need to be used with caution in biomedical research, paying special attention to its use to answer the right questions and the definition of appropriate error metrics and validation check points that confirm not only its correct use but also its relevance. All in all, DGMs provide an exciting tool that opens a bright future for the integrative analysis of single-cell -omics to understand health and disease.

Keywords: Data integration; Deep generative models; Diffusion model; Generative adversarial network; Multi-omics; Variational autoencoder; scATAC-seq; scRNA-seq.