A mixture-of-experts deep generative model for integrated analysis of single-cell multiomics data.

The recent development of single-cell multiomics analysis has enabled simultaneous detection of multiple traits at the single-cell level, providing deeper insights into cellular phenotypes and functions in diverse tissues. However, currently, it is challenging to infer the joint representations and learn relationships among multiple modalities from complex multimodal single-cell data. Here, we present scMM, a novel deep generative model-based framework for the extraction of interpretable joint representations and crossmodal generation. scMM addresses the complexity of data by leveraging a mixture-of-experts multimodal variational autoencoder. The pseudocell generation strategy of scMM compensates for the limited interpretability of deep learning models, and the proposed approach experimentally discovered multimodal regulatory programs associated with latent dimensions. Analysis of recently produced datasets validated that scMM facilitates high-resolution clustering with rich interpretability. Furthermore, we show that crossmodal generation by scMM leads to more precise prediction and data integration compared with the state-of-the-art and conventional approaches.