Antigenic Cartography

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Principles of antibody assay

Concept of Shape space

  • Basic of antigenic cartography tracks back the concept of "shape space" first propound by Perelson and Oster back in 1979.
  • In this concept, antigen and antibody are considered as 'points in an abstract shape space' with their own coordinates which consist of abstract parameters. Distances between those points denote affinity with each other.

Perelson, A. S., & Oster, G. F. (1979). Theoretical studies of clonal selection: Minimal antibody repertoire size and reliability of self-non-self discrimination. Journal of Theoretical Biology, 81(4), 645–670. https://doi.org/10.1016/0022-5193(79)90275-3

Lapedes, A., & Farber, R. (2001). The geometry of shape space: Application to influenza. Journal of Theoretical Biology, 212(1), 57–69. https://doi.org/10.1006/jtbi.2001.2347

Klingenberg, C. P. (2020). Walking on Kendall’s Shape Space: Understanding Shape Spaces and Their Coordinate Systems. Evolutionary Biology, 47(4), 334–352. https://doi.org/10.1007/s11692-020-09513-x

生形貴男. (2011). 生物のかたちの測定と比較. 化石, 89, 39–54. https://doi.org/10.14825/kaseki.89.0_39

Multidimensional scaling (MDS)

  • 多次元尺度構成法 in Japanese
  • The follwings are comprehensive reviews of multidimensional scaling

Carroll, J. D., & Arabie, P. (1980). Multidimensional Scaling. Annual Review of Psychology, 31(1), 607–649. https://doi.org/10.1146/annurev.ps.31.020180.003135

Jaworska, N., & Chupetlovska-Anastasova, A. (2009). A Review of Multidimensional Scaling (MDS) and its Utility in Various Psychological Domains. Tutorials in Quantitative Methods for Psychology, 5(1), 1–10. https://doi.org/10.20982/tqmp.05.1.p001

倉林武. (1977). 多次元尺度構成法(MDS)の紹介. 人間工学, 13(4), 137–142. https://doi.org/10.5100/jje.13.137

奥喜正. (2012). 多次元尺度法概論とそのアルゴリズム. 流通経済大学流通情報学部紀要, 17(1), 257–274. https://rku.repo.nii.ac.jp/records/4942

小杉考司. (2019, August 6). 多次元尺度構成法 その基礎と広がり. 認知心理学会テクニカルレポート. https://cogpsy.jp/wp/wp-content/uploads/COGPSY-TR-002.pdf


  • The followings are standard textbooks

Nesselroade, J. R., & Cattell, R. B. (1988). Handbook of Multivariate Experimental Psychology (J. R. Nesselroade & R. B. Cattell, Eds.; 2nd ed.). Springer US. https://doi.org/10.1007/978-1-4613-0893-5

Borg, I., Groenen, P. J. F., & Mair, P. (2018). Applied Multidimensional Scaling and Unfolding. Springer International Publishing. https://doi.org/10.1007/978-3-319-73471-2

k-Means clustering

k-means法とは?可視化してわかりやすく解説 https://hogetech.info/algorithm/kmeans

Antigenic distance

  • Prior to the development of Antigenic cartography by Derek Smith, Smith first proposed the concept of Antigenic distance in this article.

Smith, D. J., Forrest, S., Ackley, D. H., & Perelson, A. S. (1999). Variable efficacy of repeated annual influenza vaccination. Proceedings of the National Academy of Sciences of the United States of America, 96(24), 14001–14006. https://doi.org/10.1073/pnas.96.24.14001


  • Along with popularization and spread of Antigenic cartography developed in 2004 by Derek Smith, more accurate and plausible measurements of antigenic distance was proposed by Cai et al.

Cai, Z., Zhang, T., & Wan, X. F. (2012). Antigenic distance measurements for seasonal influenza vaccine selection. Vaccine, 30(2), 448–453. https://doi.org/10.1016/j.vaccine.2011.10.051

Methodology of Antigenic cartography

  • The first propounders of Antigenic Cartography were Smith DJ et al. in 2004 by using hemagluttinin inhibition (HI) assay of influenza AH3N2 viruses.

Smith, D. J., Lapedes, A. S., de Jong, J. C., Bestebroer, T. M., Rimmelzwaan, G. F., Osterhaus, A. D. M. E., & Fouchier, R. A. M. (2004). Mapping the Antigenic and Genetic Evolution of Influenza Virus. Science, 305(5682), 371–376. https://doi.org/10.1126/science.1097211


  • The followings are well documented reviews of antigenic cartography.

Sitaras, I. (2020). Antigenic cartography: Overview and current developments. In Methods in Molecular Biology (Vol. 2123, pp. 61–68). Humana Press Inc. https://doi.org/10.1007/978-1-0716-0346-8_5

Fouchier, R. A. M., & Smith, D. J. (2010). Use of Antigenic Cartography in Vaccine Seed Strain Selection. Avian Diseases, 54(s1), 220–223. https://doi.org/10.1637/8740-032509-ResNote.1

伊藤公人. (2011). インフルエンザウイルスの抗原変異とバイオインフォマティクス. ウイルス, 61(1), 3–14. https://doi.org/10.2222/jsv.61.3


  • The following resource and original articles well describe the methodology of antigenic cartography

An introduction to antigenic cartography. (n.d.). Retrieved September 18, 2023, from https://acorg.github.io/Racmacs/articles/intro-to-antigenic-cartography.html

Sitaras, I., Kalthoff, D., Beer, M., Peeters, B., & de Jong, M. C. M. (2014). Immune escape mutants of highly pathogenic avian influenza H5N1 selected using polyclonal sera: Identification of key amino acids in the HA protein. PLoS ONE, 9(2). https://doi.org/10.1371/journal.pone.0084628

Sitaras, I., Spackman, E., de Jong, M. C. M., & Parris, D. J. (2020). Selection and antigenic characterization of immune-escape mutants of H7N2 low pathogenic avian influenza virus using homologous polyclonal sera. Virus Research, 290. https://doi.org/10.1016/j.virusres.2020.198188

Various research using Antigenic cartography

  • The followings are actual research using antigenic cartography other than previously mentioned

Anderson, C. S., McCall, P. R., Stern, H. A., Yang, H., & Topham, D. J. (2018). Antigenic cartography of H1N1 influenza viruses using sequence-based antigenic distance calculation. BMC Bioinformatics, 19(1). https://doi.org/10.1186/s12859-018-2042-4

Mykytyn, A. Z., Rissmann, M., Kok, A., Rosu, M. E., Schipper, D., Breugem, T. I., van den Doel, P. B., Chandler, F., Bestebroer, T., de Wit, M., van Royen, M. E., Molenkamp, R., Oude Munnink, B. B., de Vries, R. D., GeurtsvanKessel, C., Smith, D. J., Koopmans, M. P. G., Rockx, B., Lamers, M. M., … Haagmans, B. L. (2022). Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct. Science Immunology, 7(75), 4450. https://doi.org/10.1126/sciimmunol.abq4450

Rössler, A., Netzl, A., Knabl, L., Bante, D., Wilks, S. H., Borena, W., von Laer, D., Smith, D. J., & Kimpel, J. (2023). Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography. Nature Communications, 14(1), 5224. https://doi.org/10.1038/s41467-023-41049-4