Jaswinder K. Sethi

Ladies and gentlemen - Our Atlas of Human Inflammation today out in @NatureMedicine 💫 Welcome on stage: The Cell as a Living Biomarker🩸 We Built an Inflammation Atlas of Circulating Immune Cells. By profiling more than 6.5 million peripheral blood mononuclear cells from 1,047 patients across 19 inflammatory and immune-mediated diseases using single-cell RNA sequencing, we generated a unified, high-resolution reference of immune cell states in human disease. Despite decades of research, our understanding of Inflammation has largely remained fragmented, studied one disease at a time and often confined to specific tissues. We set out to take a different approach: to ask whether inflammation leaves a shared, measurable fingerprint at the systems level of circulating immune cells and whether this signal could be leveraged for Diagnostics and ultimately Precision Medicine. Blood, unlike tissue biopsies, is accessible, repeatable, and scalable, making it an ideal substrate for liquid biopsy approaches. The key question was whether it also contains sufficient biological signal to capture disease-driving inflammatory mechanisms❓ Using interpretable machine learning approaches, specifically gradient boosted decision trees (GBDT) combined with SHAP explanations, we asked whether single cells, and ultimately patients, could be classified based solely on their blood immune transcriptomes. !!! Disease-associated gene expression signatures enabled accurate classification within the study cohort, reinforcing the concept that immune cells in circulation function as “Living Biomarkers”🩸 We are now working toward a diagnostic prototype that brings these concepts closer to clinical reality. Together with hospital and industry partners, we aim to develop Foundation Models of immune cell plasticity that can operate across diseases and settings, enabling patient stratification, therapy monitoring, and outcome prediction from blood alone. Our long-term vision is a future in which a simple blood draw provides a systems-level readout of immune health, guiding diagnosis and treatment across inflammatory diseases. Immune cells are already doing the sensing. The challenge and opportunity is to learn how to listen. Please find the Nature Medicine Paper here: lnkd.in/eYV7pwrN