How can we spot when avian influenza jumps between species? The answer lies in FluWarning, a digital platform that flags unusual changes in flu virus genomes. Developed by researchers from Politecnico di Milano and the University of Milan, the system scans viral genetic code for subtle but significant mutations that may signal spillover—from birds to cattle or to humans.
The study, recently published in Science Advances, was carried out under the SENSIBLE project (Small‑data Early WarNing System for viral Pathogens In puBLic hEalth). The FluWarning team includes Anna Bernasconi, Professor Stefano Ceri and researcher Tommaso Alfonsi from the Department of Electronics, Information and Bioengineering at Politecnico di Milano, and Professor Matteo Chiara of the University of Milan’s Biosciences Department.
Data from GISAID, a global repository of virus sequences and accompanying metadata, formed the basis of the research. FluWarning was first trained on sequences from the 2009 H1N1 swine flu outbreak, a well‑documented case of animal‑to‑human transmission. It was then applied to the H5N1 avian strain, which, over the past year, has also been found in U.S. cattle.
The platform employs a statistical anomaly‑detection algorithm. Depending on configuration, it can flag individual sequences or clusters of anomalous sequences. FluWarning learns the typical genetic patterns of influenza viruses and issues a warning whenever a sequence differs markedly. Each alert is reviewed by virologists to confirm or dismiss potential spillover events.
- Reassortant virus. Credit: Politecnico di Milano
- FluWarning's alert system. Credit: Politecnico di Milano
“Its straightforward installation and the ability to analyze data for specific regions and timeframes make FluWarning accessible to many laboratories and regional genomic surveillance units,” Bernasconi explains. “The system is fully operational and can provide daily updates on genetic changes.”
During 2024–2025, two H5N1 genotypes were linked to separate outbreaks in the United States, with many dairy cattle testing positive for bird flu.
“FluWarning detected viral activity clusters in several U.S. states, notably California, where an emergency was declared on 18 December 2024 due to cattle‑to‑bird flu concerns,” Chiara reports. “The system even flagged alerts before official notifications appeared and identified key mutations in the hemagglutinin (HA) gene, the protein that determines host cell entry.”
The tool tracked viral evolution and pinpointed characteristic markers of the Californian strains.
“FluWarning represents a major advance for identifying viral changes that could threaten animals or humans,” Ceri concludes. “By making this technology widely available, we aim to strengthen global surveillance for this critical health issue.”