Genomic similarity to quantitatively evaluate the reassortment potential of H7N9 with other subtypes of avian influenza viruses.

Abstract

INTRODUCTION: The H7N9 influenza virus poses a significant public health threat due to its potential for reassortment and cross-species transmission. This study aims to systematically evaluate the genomic similarity between H7N9 and other influenza A subtypes to identify strains with high reassortment potential and characterize their spatiotemporal and host distribution patterns. METHODS: We analyzed nearly 4,000 H7N9 sequences from GISAID and NCBI, alongside representative sequences of other influenza A subtypes. Open reading frames were extracted, and a genomic similarity index was constructed using Euclidean distance, dot product, and cosine similarity measures, with weights optimized via principal component analysis. The index was applied to quantify inter-subtype similarity and predict reassortment-prone strains. RESULTS: High sequence similarity was observed between H7N9 and cognate subtypes (e.g., H7N3, H15N9), with H7N3 exhibiting the highest similarity index (1.00). Validation using known reassortant strains, such as A/Yixing/805/2022 (H3N2), confirmed that strains with high reassortment potential showed significantly elevated similarity scores across all gene segments (p< 0.001). High-similarity outliers analysis identified 581 spillover events, temporally concentrated during 2014-2017, and spatially clustered in regions like the United States, Europe, and Hong Kong. Host analysis highlighted birds-especially chickens, ducks, and turkeys-as key reservoirs for reassortment. DISCUSSION: The genomic similarity index effectively identifies influenza A subtypes with high reassortment potential, supported by retrospective validation and spatiotemporal congruence with documented outbreaks. The concentration of high-similarity strains in specific hosts and regions underscores the role of ecological factors in viral evolution. These findings provide a predictive framework for monitoring emergent reassortants and inform targeted surveillance strategies.