Inferring gene regulatory networks by hypergraph generative model

Summary We present hypergraph variational autoencoder (HyperG-VAE), a Bayesian deep generative model that leverages hypergraph representation to model single-cell RNA sequencing (scRNA-seq) data. The model features a cell encoder with a structural equation model to account for cellular heterogeneity and construct gene regulatory networks (GRNs) alongside a gene encoder using hypergraph self-attention to identify gene modules. The synergistic optimization of encoders via a decoder improves GRN inference, single-cell clustering, and data visualization, as validated by benchmarks. HyperG-VAE effectively uncovers gene regulation patterns and demonstrates robustness in downstream analyses, as shown in B cell development data from bone marrow. Gene set enrichment analysis of overlapping genes in predicted GRNs confirms the gene encoder’s role in refining GRN inference. Offering an efficient solution for scRNA-seq analysis and GRN construction, HyperG-VAE also holds the potential for extending GRN modeling to temporal and multimodal single-cell omics.