Researchers from the National Center for Genomic Analysis (CNAG) have published the first cellular atlas of inflammation, a comprehensive database that analysed more than 6.5 million blood cells from 1,000 individuals, including both healthy subjects and patients with 19 different diseases. This CNAG study, based at the Barcelona Science Park, in collaboration with the École Polytechnique Fédérale de Lausanne (EPFL, Switzerland), has been published in the journal Nature Medicine and lays the groundwork for the development of precision diagnostic tools, enabling faster identification of patients with autoimmune and inflammatory diseases, infections, and tumours, such as breast or colorectal cancer.

The study proposes an innovative approach: turning the cells themselves into biomarkers, key to helping uncover some of the mysteries underlying pathological inflammatory conditions. “Immune cells in the blood carry footprints of disease, which they acquire as they circulate through our system. Reading them at cellular resolution allows us to turn cells into living biomarkers, contributing to the generation of precision diagnostics,” explains Dr. Holger Heyn, lead author of the study and head of the Single-Cell Genomics Group at CNAG. “We provide proof of concept for turning immune cells into a universal diagnostic tool, a concept we are now taking into the clinical prototyping phase.”

The research analyses inflammatory signals from immune cells in the blood and what they can reveal about the diseases affecting patients. Through detailed analysis of the different cellular states that drive disease progression, the study shows how inflammation changes depending on the condition. Using the new cellular atlas, researchers identified molecular indicators that act as guiding signals, leading to a deeper understanding of the underlying biology and enabling precise classification of these diseases. To identify these signals, the researchers analysed inflammatory genes that coordinate the immune response, identifying programs that activate immune cells, guide their movement, defend against harmful agents, and trigger defence mechanisms.

This genetic knowledge helps differentiate each disease and classify patients according to their unique inflammatory signatures. In the case of systemic lupus erythematosus, an aggressive autoimmune disorder, the maps revealed that certain immune cellular states are associated with more severe forms of the disease. One of the key signals involved is the interferon response, a natural defence mechanism that normally helps fight viruses. In lupus, this signal is constantly active, which can overstimulate the immune system and worsen inflammation. This discovery helps researchers understand why some cases become chronic and more aggressive.

A generative artificial intelligence tool that learns from inflammatory states

In addition to applying the latest single-cell genomics techniques available at CNAG, the research introduces a second innovation: the use of AI to classify patients based on data from individual cells that make up the different maps of the inflammation atlas. The researchers developed a generative AI model capable of learning from the cellular states and genetic activity captured in the atlas, with the aim of projecting biological patterns onto future patients.

This new approach lays the foundation for a precision medicine tool that could accelerate diagnosis and guide more personalized treatments, improving both quality of life and clinical management for individuals affected by diseases with inflammatory conditions. Dr. Juan Nieto, an immunologist in the Single-Cell Genomics Group at CNAG and also a lead author of the study, notes: “This atlas helps us move toward more personalized care. By understanding the specific inflammatory patterns of each patient, clinicians could select treatments earlier and more accurately, reducing trial and error and improving patient care.”

Following the publication of this open-access resource, which has already been tested with patient samples as a personalized diagnostic tool, the researchers are now working on the next phase of the project. Their efforts focus on establishing the protocols necessary to ensure data quality and standardization, with the goal of building a solid foundation that will allow its integration into clinical practice, making it accessible to hospitals and healthcare institutions in the future.

The study was made possible thanks to data from DocTIS, a multicenter project funded by the European Union aimed at improving treatment effectiveness in inflammatory diseases of the immune system, as well as through collaboration with an extensive network of national and European hospitals.

» Article of reference: Jiménez-Gracia, L., Maspero, D., Aguilar-Fernández, S. et al. Interpretable inflammation landscape of circulating immune cells. Nat Med (2026). Doi: 10.1038/s41591-025-04126-3

» Link to the news: CNAG website [+]