SCANCell reveals diverse inter-cluster interaction patterns in systemic lupus erythematosus across the disease spectrum.

MOTIVATION High-dimensional mass cytometry (CyTOF), which provides both cellular signatures and inter-cluster interactions like the antagonism between immune activation and suppression, and the pro-inflammatory synergy, sheds light on the cellular and molecular basis of disease pathogenesis. However, revealing the aberrance of inter-cluster communication networks in CyTOF datasets remains a significant challenge. RESULTS Here, we developed Sample Classification and direct Association Network among Cell clusters (SCANCell) that quantifies the direct association (DA) network of cell clusters. SCANCell was applied to profile inter-cluster interaction patterns of a well-recruited systemic lupus erythematosus (SLE) cohort, including eight healthy controls (HCs), ten active SLE patients (APs), and eight remission SLE patients (RPs). SCANCell identified decreased inter-cluster interactions of CD8+ T cells in APs compared to RPs, and enhanced DA of CD8+ T cells after stimulation with immunostimulatory cytokine interleukin-2 in vitro. These discoveries prove that SCANCell can uncover pathology- and drug stimulation- associated inter-cluster interactions, which potentially benefits understanding of pathogenesis and novel therapeutic strategies. AVAILABILITY The main processing scripts of SCNACell are available at https://github.com/Lxc417/SCANCell. Other codes for the following data statistics are available from the corresponding author upon request. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.