Systematic investigation of cytokine signaling activity at the tissue and single-cell levels

CytoSig, an interactive database and model to predict cytokine signaling activity at bulk and single-cell levels. Cytokines are critical for intercellular communication in human health and disease, but the investigation of cytokine signaling activity has remained challenging due to the short half-lives of cytokines and the complexity/redundancy of cytokine functions. To address these challenges, we developed the Cytokine Signaling Analyzer (CytoSig; ), providing both a database of target genes modulated by cytokines and a predictive model of cytokine signaling cascades from transcriptomic profiles. We collected 20,591 transcriptome profiles for human cytokine, chemokine and growth factor responses. This atlas of transcriptional patterns induced by cytokines enabled the reliable prediction of signaling activities in distinct cell populations in infectious diseases, chronic inflammation and cancer using bulk and single-cell transcriptomic data. CytoSig revealed previously unidentified roles of many cytokines, such as BMP6 as an anti-inflammatory factor, and identified candidate therapeutic targets in human inflammatory diseases, such as CXCL8 for severe coronavirus disease 2019.

Automated summary

CytoSig is an interactive database and model for predicting cytokine signaling activity at bulk and single-cell levels. By analyzing 20,591 transcriptome profiles, it enables reliable prediction of signaling activities in different cell populations and reveals previously unknown roles of many cytokines.