sc-ImmuCC: hierarchical annotation for immune cell types in single-cell RNA-seq.

Accurately identifying immune cell types in single-cell RNA-sequencing (scRNA-Seq) data is critical to uncovering immune responses in health or disease conditions. However, the high heterogeneity and sparsity of scRNA-Seq data, as well as the similarity in gene expression among immune cell types, poses a great challenge for accurate identification of immune cell types in scRNA-Seq data. Here, we developed a tool named sc-ImmuCC for hierarchical annotation of immune cell types from scRNA-Seq data, based on the optimized gene sets and ssGSEA algorithm. sc-ImmuCC simulates the natural differentiation of immune cells, and the hierarchical annotation includes three layers, which can annotate nine major immune cell types and 29 cell subtypes. The test results showed its stable performance and strong consistency among different tissue datasets with average accuracy of 71-90%. In addition, the optimized gene sets and hierarchical annotation strategy could be applied to other methods to improve their annotation accuracy and the spectrum of annotated cell types and subtypes. We also applied sc-ImmuCC to a dataset composed of COVID-19, influenza, and healthy donors, and found that the proportion of monocytes in patients with COVID-19 and influenza was significantly higher than that in healthy people. The easy-to-use sc-ImmuCC tool provides a good way to comprehensively annotate immune cell types from scRNA-Seq data, and will also help study the immune mechanism underlying physiological and pathological conditions.