MTGO-SC, A Tool to Explore Gene Modules in Single-Cell RNA Sequencing Data.

The identification of functional modules in gene interaction networks is a key step in understanding biological processes. Network interpretation is essential for unveiling biological mechanisms, candidate biomarkers, or potential targets for drug discovery/repositioning. Plenty of biological module identification algorithms are available, although none is explicitly designed to perform the task on single-cell RNA sequencing (scRNA-seq) data. Here, we introduce MTGO-SC, an adaptation for scRNA-seq of our biological network module detection algorithm MTGO. MTGO-SC isolates gene functional modules by leveraging on both the network topological structure and the annotations characterizing the nodes (genes). These annotations are provided by an external source, such as databases and literature repositories (e.g., the Gene Ontology, Reactome). Thanks to the depth of single-cell data, it is possible to define one network for each cell cluster (typically, cell type or state) composing each sample, as opposed to traditional bulk RNA-seq, where the emerging gene network is averaged over the whole sample. MTGO-SC provides two complexity levels for interpretation: the gene-gene interaction and the intermodule interaction networks. MTGO-SC is versatile in letting the users define the rules to extract the gene network and integrated with the Seurat scRNA-seq analysis pipeline. MTGO-SC is available at https://github.com/ne1s0n/MTGOsc.