title: Predicting the Mutating Distribution at Antigenic Sites of the Influenza Virus.
abstract: Mutations of the influenza virus lead to antigenic changes that cause recurrent epidemics and vaccine resistance. Preventive measures would benefit greatly from the ability to predict the potential distribution of new antigenic sites in future strains. By leveraging the extensive historical records of HA sequences for 90 years, we designed a computational model to simulate the dynamic evolution of antigenic sites in A/H1N1. With templates of antigenic sequences, the model can effectively predict the potential distribution of future antigenic mutants. Validation on 10932 HA sequences from the last 16 years showing that the mutated antigenic sites of over 94% of reported strains fell in our predicted profile. Meanwhile, our model can successfully capture 96% of antigenic sites in those dominant epitopes. Similar results are observed on the complete set of H3N2 historical data, supporting the general applicability of our model to multiple sub-types of influenza. Our results suggest that the mutational profile of future antigenic sites can be predicted based on historical evolutionary traces despite the widespread, random mutations in influenza. Coupled with closely monitored sequence data from influenza surveillance networks, our method can help to forecast changes in viral antigenicity for seasonal flu and inform public health interventions.
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.|Department of Computational Regulatory Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.|The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an, China.
authors.forename: Shuning
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Ruixin
authors.initials: R
authors.lastname: Zhu
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Qiu
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Qiu
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Qingchen
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Computational Regulatory Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yungang
authors.initials: Y
authors.lastname: He
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Tang
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.|Shanghai Center for Bioinformation technology, Shanghai, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Cao
mesh_terms: D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D003198:Computer Simulation; D019143:Evolution, Molecular; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000821:virology; D008957:Models, Genetic; D009154:Mutation
chemical_list: D000956:Antigens, Viral
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