Efficient Generation of Paired Single‐Cell Multiomics Profiles by Deep Learning

Recent advances in single‐cell sequencing technology have made it possible to measure multiple paired omics simultaneously in a single cell such as cellular indexing of transcriptomes and epitopes by sequencing (CITE‐seq) and single‐nucleus chromatin accessibility and mRNA expression sequencing (SNARE‐seq). However, the widespread application of these single‐cell multiomics profiling technologies has been limited by their experimental complexity, noise in nature, and high cost. In addition, single‐omics sequencing technologies have generated tremendous and high‐quality single‐cell datasets but have yet to be fully utilized. Here, single‐cell multiomics generation (scMOG), a deep learning‐based framework to generate single‐cell assay for transposase‐accessible chromatin (ATAC) data in silico is developed from experimentally available single‐cell RNA‐seq measurements and vice versa. The results demonstrate that scMOG can accurately perform cross‐omics generation between RNA and ATAC, and generate paired multiomics data with biological meanings when one omics is experimentally unavailable and out of training datasets. The generated ATAC, either alone or in combination with measured RNA, exhibits equivalent or superior performance to that of the experimentally measured counterparts throughout multiple downstream analyses. scMOG is also applied to human lymphoma data, which proves to be more effective in identifying tumor samples than the experimentally measured ATAC data. Finally, the performance of scMOG is investigated in other omics such as proteomics and it still shows robust performance on surface protein generation.