Interpretable Inflammation Landscape of Circulating Immune cells (ILCIC_HealthyExercise)

Inflammation is a biological phenomenon beneficial for homeostasis, but unfavorable if dysregulated. Although major progress has been made in characterizing inflammation in specific diseases, a global, holistic understanding is still elusive. This is particularly intriguing, considering its function for human health and the potential for modern medicine if fully deciphered. Here, we leveraged advances in single-cell transcriptomics to delineate inflammatory processes of circulating immune cells during infection, immune-mediated inflammatory diseases and cancer. Our single-cell atlas of >6.5 million peripheral blood mononuclear cells from 1047 patients (56% female, 43% male) and 19 diseases allowed us to learn a comprehensive model of inflammation in circulating immune cells. The atlas expanded our current knowledge of the biology of inflammation of immune-mediated diseases, acute and chronic inflammatory diseases, infection and solid tumors, and laid the foundation to develop a disease classification framework using unsupervised as well as explainable machine learning. Beyond a disease-centered analysis, we charted altered activity of inflammatory molecules in peripheral blood cells, depicting discriminative inflammation-related genes to further understand mechanisms of inflammation. We present a rich resource for the community, and laid the groundwork for learning a classifier for inflammatory diseases, presenting cells in circulation as a potential tool for disease classification. Overall design: scRNA-seq from 8 human PBMC samples from healthy donors, undergoing different physical activity (4 active and 4 inactive).