Prediction of antigenic evolution of influenza viruses through Bayesian estimation using statistics on strings

• Project/Area Number: 16H02863
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Intelligent informatics
• Research Institution: Hokkaido University
• Principal Investigator: Ito Kimihito 北海道大学, 人獣共通感染症リサーチセンター, 教授 (60396314)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: インフルエンザウイルス / 抗原変異 / データ同化 / 粒子フィルタ / インフルエンザ / 変異予測 / 抗原変異予測 / 文字列統計量 / ベイズ推定 / 文字列推定量

Outline of Final Research Achievements

By integrating the quasi spices theory with infectious disease modelling, we developed a mathematical model of viral sequences, infection, and herd immunity. Actual observations of viral sequences and the number of reported cases of H1N1 2009 pandemic viruses were integrated into computer simulations, and parameters in the model were estimated by the data assimilation technique called the particle filter. For every 30 days 100,000 simulations were ran and filter distributions of parameters were calculated using amino acid sequences observed in the corresponding periods. Six-month period predictions were made using the estimated parameters. As a result, the developed method predicts the actual amino acid substitutions on the hemagglutinin molecule with a precision ratio of 79% and recall ratio of 53% .

Academic Significance and Societal Importance of the Research Achievements

インフルエンザの予防にはワクチン接種が有効であるが，人の免疫圧による選択淘汰を受けてウイルスの遺伝子が変異し続けるため， ワクチン株を頻繁に更新しなければならない。そこで，本研究では，ワクチン株を先回りして準備するために，感染症数理疫学と集団遺伝学を融合し，ウイルスの遺伝子配列の文字列統計量から，感染症流行モデルのパラメータを推定する手法を開発し，その予測精度を明らかにした。本手法は 6カ月後のアミノ酸置換を，適合率79%，再現率53%で予測できることが明らかになり，今後のワクチン政策への応用が期待される。

Research Products

• [Int'l Joint Research] Icahn School of Medicine at Mount Sinai(米国)
• [Journal Article] Influenza Virus Infection Induces a Narrow Antibody Response in Children but a Broad Recall Response in Adults (2020)
  • Author(s): Meade Philip、Kuan Guillermina、Strohmeier Shirin、Maier Hannah E.、Amanat Fatima、Balmaseda Angel、Ito Kimihito、Kirkpatrick Ericka、Javier Andres、Gresh Lionel、Nachbagauer Raffael、Gordon Aubree、Krammer Florian
  • Journal Title: mBio Volume: 11 Issue: 1
  • DOI: 10.1128/mbio.03243-19
• [Journal Article] Fowl Adenovirus (FAdV) Recombination with Intertypic Crossovers in Genomes of FAdV-D and FAdV-E, Displaying Hybrid Serological Phenotypes (2019)
  • Author(s): Schachner Anna、Gonzalez Gabriel、Endler Lukas、Ito Kimihito、Hess Michael
  • Journal Title: Viruses Volume: 11 Issue: 12 Pages: 1094-1094
  • DOI: 10.3390/v11121094
• [Journal Article] Estimating Transmission Potential of H5N1 Viruses Among Humans in Egypt Using Phylogeny, Genetic Distance and Sampling Time Interval (2019)
  • Author(s): Mohamed Wessam、Ito Kimihito、Omori Ryosuke
  • Journal Title: Frontiers in Microbiology Volume: 10 Pages: 2765-2765
  • DOI: 10.3389/fmicb.2019.02765
• [Journal Article] 季節性インフルエンザの流行予測 (2019)
  • Author(s): 渡邉真治，伊藤公人，佐藤裕徳
  • Journal Title: インフルエンザ Volume: 20 Pages: 205-210
• [Journal Article] Inferring epidemiological dynamics of infectious diseases using Tajima's D statistic on nucleotide sequences of pathogens (2017)
  • Author(s): Kim Kiyeon、Omori Ryosuke、Ito Kimihito
  • Journal Title: Epidemics Volume: 21 Pages: 21-29
  • DOI: 10.1016/j.epidem.2017.04.004
  • Peer Reviewed / Open Access
• [Journal Article] Identification of the same polyomavirus species in different African horseshoe bat species is indicative of short-range host-switching events (2017)
  • Author(s): Carr M, Gonzalez G, Sasaki M, Dool SE, Ito K, Ishii A, Hang'ombe BM, Mweene AS, Teeling EC, Hall WW, Orba Y, Sawa H
  • Journal Title: Journal of General Virology Volume: 98 Issue: 11 Pages: 2771-2785
  • DOI: 10.1099/jgv.0.000935
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Discovery of African bat polyomaviruses and infrequent recombination in the large T antigen in the Polyomaviridae. (2017)
  • Author(s): Carr M, Gonzalez G, Sasaki M, Ito K, Ishii A, Hangombe BM, Mweene AS, Orba Y, Sawa H
  • Journal Title: Journal of General Virology Volume: 98(4) Issue: 4 Pages: 726-738
  • DOI: 10.1099/jgv.0.000737
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular dynamics simulation of the influenza A(H3N2) hemagglutinin trimer reveals the structural basis for adaptive evolution of the recent epidemic clade 3C.2a (2017)
  • Author(s): Yokoyama M, Fujisaki S, Shirakura M, Watanabe S, Odagiri T, Ito K, Sato H
  • Journal Title: Frontiers in Microbiology Volume: 8 Pages: 584-584
  • DOI: 10.3389/fmicb.2017.00584
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Defining the antibody cross-reactome against the influenza virus surface glycoproteins (2017)
  • Author(s): Nachbagauer R, Choi A, Hirsh A, Margine I, Iida S, Barrera A, Ferres M, Albrecht RA, Garcia-Sastre A, Bouvier NM, Ito K, Medina RA, Palese P, Krammer F
  • Journal Title: Nature Immunol Volume: [Epub ahead of print] Issue: 4 Pages: 464-473
  • DOI: 10.1038/ni.3684
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An optimistic protein assembly from sequence reads salvaged an uncharacterized segment of mouse picobirnavirus. (2017)
  • Author(s): Gonzalez G, Sasaki M, Kamiya T, Burkitt-Gray L, Tsuji NM, Sawa H, Ito K.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 40447-40447
  • DOI: 10.1038/srep40447
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Isolation of a simian immunodeficiency virus from a malbrouck (Chlorocebus cynosuros). (2016)
  • Author(s): Carr M, Kawaguchi A, Sasaki M, Gonzalez G, Ito K, Thomas Y, Hang'ombe BM, Mweene AS, Zhao G, Wang D, Orba Y, Ishii A, Sawa H.
  • Journal Title: Arch Virol. Volume: 162 Issue: 2 Pages: 543-548
  • DOI: 10.1007/s00705-016-3129-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tracking the evolution of polymerase genes of influenza A viruses during interspecies transmission between avian and swine hosts (2016)
  • Author(s): Karnbunchob N, Omori R, Tessmer H, Ito K
  • Journal Title: Front Microbiol Volume: 7 Pages: 2118-2118
  • DOI: 10.3389/fmicb.2016.02118
  • NAID: 120005955478
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Estimating the Lineage Dynamics of Human Influenza B Viruses (2016)
  • Author(s): Mayumbo Nyirenda, Ryosuke Omori, Heidi L. Tessmer, Hiroki Arimura, Kimihito Ito
  • Journal Title: PLoS ONE Volume: 11(11) Issue: 11 Pages: e0166107-e0166107
  • DOI: 10.1371/journal.pone.0166107
  • NAID: 120005946864
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multi-reassortant G3P[3] group A rotavirus in a horseshoe bat in Zambia. (2016)
  • Author(s): Sasaki M, Orba Y, Sasaki S, Gonzalez G, Ishii A, Hang'ombe BM, Mweene AS, Ito K, Sawa H.
  • Journal Title: J Gen Virol. Volume: 97 Issue: 10 Pages: 2488-2493
  • DOI: 10.1099/jgv.0.000591
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Divergent bufavirus harboured in megabats represents a new lineage of parvoviruses (2016)
  • Author(s): Sasaki M, Gonzalez G, Wada Y, Setiyono A, Handharyani E, Rahmadani I, Taha S, Adiani S, Latief M, Kholilullah ZA, Subangkit M, Kobayashi S, Nakamura I, Kimura T, Orba Y, Ito K, Sawa H
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 24257-24257
  • DOI: 10.1038/srep24257
  • NAID: 120005906794
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Inferring epidemiological dynamics of infectious diseases using Tajima's D statistic on nucleotide sequences of pathogens (2017)
  • Author(s): Ito Kimihito、Kim Kiyeon、Omori Ryosuke
  • Organizer: Epidemics6 - International Conference on Infectious Disease Dynamics
  • Int'l Joint Research
• [Presentation] 病原体の集団遺伝学と感染症の数理疫学の融合 (2017)
  • Author(s): 伊藤公人
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 仙台国際センター，仙台
  • Invited
• [Presentation] バイオインフォマティクスによるインフルエンザウイルス研究 (2017)
  • Author(s): 伊藤公人
  • Organizer: 新興・再興感染症制御プロジェクト 新興再興事業・J-GRID合同シンポジウム 『感染症研究連携のフロンティア』
  • Place of Presentation: 国立感染症研究所，東京
• [Presentation] インフルエンザウイルスの集団遺伝学 (2016)
  • Author(s): 伊藤公人
  • Organizer: ゲノム多様性解析ワークショップ
  • Place of Presentation: 北海道大学学術交流会館，札幌
  • Year and Date: 2016-12-05
• [Presentation] Predicting antigenic changes of influenza viruses through data assimilation (2016)
  • Author(s): Kimihito Ito
  • Organizer: Innovative Mathematical Modeling for the Analysis of Infectious Disease Data
  • Place of Presentation: 神戸大学瀧川記念学術交流会館，神戸
  • Year and Date: 2016-10-11
  • Int'l Joint Research
• [Presentation] Prediction using evolutionary statistics of influenza A viruses (2016)
  • Author(s): Kimihito Ito
  • Organizer: Modelling Influenza Conference
  • Place of Presentation: Princeton University, Princeton, USA
  • Year and Date: 2016-07-06
  • Int'l Joint Research