A heterogeneous graph cross-omics attention model for single-cell representation learning

Abstract

Single-cell multi-omics sequencing technologies allow simultaneous measurement of transcriptome and epigenome profiles in the same cell, providing unprecedented opportunities to dissect cell heterogeneity. Despite great efforts, conjoint analysis of single-cell multi-omics data still suffers from sparsity, high dimensionality and binary. In this study, we present a heterogeneous graph cross-omics attention model (scHGA), a computational tool based on a heterogeneous graph neural network combining two attention mechanisms to jointly analyze single-cell multi-omics data based on different protocols data, including SNARE-seq, scMT-seq and sci-CAR. To avoid the cell heterogeneity of single-omics data, scHGA automatically learns a cell association graph to capture neighbor information. The latent representation of aggregated cells generated by hierarchical attention can fuse knowledge across different omics to dissect cellular heterogeneity, providing a better scheme to characterize the features of cells. scHGA is an effective exploration of graph neural networks in single-cell multi-omics analysis, providing new insights into the understanding of single-cell sequencing data.