A novel approach to profile global circulation pathway of SARS-CoV-2 variants by site-based mutation dynamics

Hong Zheng; Shimin Su; Caiqi Liu; Jingzhi Lou; Lirong Cao; Yexian Zhang; Zhihui Zhang; Marc Ka Chun Chong; Benny Chung-Ying Zee; Peter Pak-Hang Cheung; Haogao Gu; Juan Pu; Leo Lit Man Poon; Hui-Ling Yen; Maggie Haitian Wang

arXiv · 2511.22841

A novel approach to profile global circulation pathway of SARS-CoV-2 variants by site-based mutation dynamics

Hong Zheng·Shimin Su·Caiqi Liu·Jingzhi Lou·Lirong Cao·Yexian Zhang·Zhihui Zhang·Marc Ka Chun Chong·Benny Chung-Ying Zee·Peter Pak-Hang Cheung·Haogao Gu·Juan Pu·Leo Lit Man Poon·Hui-Ling Yen·Maggie Haitian Wang

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Abstract

The genetic evolution of SARS-CoV-2 has caused recurring epidemic waves, understanding its global dispersal patterns is critical for effective surveillance. We developed the Site-based mutation dynamics - Equal Power Sampling (S-EPS) framework, a phylogenetic-free, bias-correcting framework for profiling viral source-sink dynamics. Applying S-EPS to 6.6 million SARS-CoV-2 genomes (March 2020 - June 2024) from 13 regions worldwide, we identified Africa and the Indian subcontinent as the predominant sources of key mutations. Southeast Asia serves as an early transmission hub, while Russia and South America mainly acted as sinks. Key mutations took longer to establish fitness in source regions than externally. Once an amino acid substitution on the receptor-binding domain reached 1% prevalence in major sources, there is an 80% probability it would spread elsewhere, with a 2-month median lead time (IQR: 1-4). Our findings underscore the importance of genetic surveillance, with S-EPS offering enhanced capability for monitoring emerging viral threats.

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Hong Zheng, Shimin Su, Caiqi Liu, Jingzhi Lou, Lirong Cao, Yexian Zhang, Zhihui Zhang, Marc Ka Chun Chong, Benny Chung-Ying Zee, Peter Pak-Hang Cheung, Haogao Gu, Juan Pu, Leo Lit Man Poon, Hui-Ling Yen, Maggie Haitian Wang. 2025-11-28. A novel approach to profile global circulation pathway of SARS-CoV-2 variants by site-based mutation dynamics. https://arxiv.org/abs/2511.22841

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