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 8 healthy controls, 10 active SLE patients (APs) and 8 remission SLE patients (RPs). SCANCell identified decreased inter-cluster interactions of CD8(+) T cells in APs compared with 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.

Automated summary

This study developed a method called SCANCell to quantify the direct association network of cell clusters and applied it to a systemic lupus erythematosus cohort. The results showed that SCANCell can reveal inter-cluster interactions and provide insights into disease pathogenesis and therapeutic strategies.