Single-cell multi-omics (scMulti-omics) allows the quantification of multiple modalities simultaneously to capture the intricacy of complex molecular mechanisms and cellular heterogeneity. Existing tools cannot effectively infer the active biological networks in diverse cell types and the response of these networks to external stimuli. Researchers from The Ohio State University have developed DeepMAPS for biological network inference from scMulti-omics. It models scMulti-omics in a heterogeneous graph and learns relations among cells and genes within both local and global contexts in a robust manner using a multi-head graph transformer. Benchmarking results indicate DeepMAPS performs better than existing tools in cell clustering and biological network construction. It also showcases competitive capability in deriving cell-type-specific biological networks in lung tumor leukocyte CITE-seq data and matched diffuse small lymphocytic lymphoma scRNA-seq and scATAC-seq data. In addition, we deploy a DeepMAPS webserver equipped with multiple functionalities and visualizations to improve the usability and reproducibility of scMulti-omics data analysis.
The workflow of DeepMAPS and HGT illustration
a The overall framework of DeepMAPS. Five main steps were included in carrying out cell clustering and biological gene network inference from the input scMulti-omics data. b The graph autoencoder was inserted with a HGT model. The integrated cell-gene matrix was used to build a heterogeneous graph include all cells (green) and genes (purple) as nodes. The HGT model is trained on multiple subgraphs (50 subgraphs as an example) that cover nodes in the whole graph as many as possible. Each subgraph is used to train the model with 100 epochs; thus, the whole training process iterates 5,000 times. The trained model is then applied to the whole graph to learn and update the embeddings of each node. c An illustration of embedding update process of the target node in a single HGT layer. The red circle in the upper panel indicates the target node and the black circle indicates the source nodes. Arrows represents for the connection between a target node and source nodes. Colored rectangles represent for embeddings of different nodes. The zoom in detailed process in the bottom panel shows the massage passing process and attention mechanism. The final output of one HGT layer is an update of node embedding for all nodes. HGT heterogeneous graph transformer.