Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure
Fig 4
Spike evolution of the 2009 influenza pandemic and SARS-CoV-2.
Comparison of the diversity of sequences (mutability map) and the on-rate maps. For A-B, panel i depicts the residue entropy as a function at different positions. For A-B, panel ii depicts the entropy of the residues is superimposed on the spike. Same color coding as in Fig 1C-ii. Panel iii. Scatter plot of the entropy of epitope clusters, against the epitope cluster on-rate computed for the spike. (A) Sequence entropy of HA for the pandemic flu H1N1 (2009–2017) (sequences taken from www.gisaid.org, and [40]). The correlation coefficient between the epitope cluster entropy and on-rate is R = 0.18. (B) Sequence entropy of the S spike protein of SARS-CoV-2 computed for all S protein sequences up to May 31st 2021 (sequences downloaded from www.gisaid.org). The correlation coefficient between the epitope cluster entropy and epitope cluster on-rate is R = 0.058. Same legend as Fig 3F. Time-dependence sequence entropy of SARS-CoV-2. The entropy of the S spike protein of SARS-CoV-2 computed for sequences collected at 5 time periods since the beginning of the pandemic (panel i) and correlation to the on-rate map, following epitope clustering (panel ii) (same clusters as those shown and used in Fig 3D-ii and 3F). (C) up to February 1st 2020, R = -0.16, (D) February-May 2020, R = -0.079 (E) June-November 2020, R = 0.3, (F) December 2020, R = 0.39, (G) January-May 2021, R = 0.061. (H) The correlation coefficient as a function of time. (Find an interactive, comparison of the time-dependent mutability map to the on-rate map here https://amitaiassaf.github.io/SpikeGeometry/SARSCoV2EvoT.html). Functional role of SARS-CoV-2 spike mutations. (I) Residues where key mutations were identified in SARS-CoV-2 variants are marked with colored beads. Residues were ranked based on their on-rate (targeting) by Abs according to the model prediction. The upper 66th on-rate percentile rank is the threshold between “high on-rate” (mutation due to escape) and “low on-rate” (mutation due to other factors) residues. Red residues have high on-rate and mutations in them were found to confer Ab escape (true positives) [Residue positions: 136, 140, 141, 143, 244, 345, 441, 444, 447, 449, 450, 452, 489, 490 493, 499, and 501]. Blue residues have a high on-rate and mutations in them have not been shown as of yet to not confer Ab escape (false positives) [Residues: 69, 80, and 138]. Green residues have a low on-rate and mutations in them do not confer Ab escape (true negatives) [Residues: 614, 655, and 701]. Orange residues have a low on-rate and mutations in them confer Ab escape (false negatives) [Residues: 346, 439, and 453]. Yellow residues have a high on-rate but it is unknown whether mutations in them confer Ab escape [Residues: 102, 367]. See S1 Data for a complete list.