Summary of how mutations affect both antibody escape and cell entry
Interactive plot of both antibody escape and cell entry
The plot below shows how mutations affect antibody escape from all six antibodies and cell entry, and allows you to zoom and mouseover sites and mutations. Positive cell entry values indicate better entry than the parental GPC while negative values indicate impaired entry. Positive escape values indicate reduced neutralization by an antibody while negative values indicate more neutralization. Note that the two different shades of gray in the heatmaps have differing meanings: light gray means a mutation was missing (not measured) in the library, whereas dark gray means a mutation was measured but was so deleterious for cell entry it is not possible to reliably estimate its effect on antibody escape (the threshold for how deleterious a mutation must be for cell entry to be shown in dark gray is controlled by the cell entry slider at the bottom of the plot).
Here is an explanation of the key plot elements:
- The zoom bar at the top of the plot shows different regions of GPC, and can be used to zoom in on specific sites.
- The line plots summarize the average escape from neutralization by all six monoclonal antibodies, and then below that in gray the escape for each individual antibody. The height of each line summarizes the total escape caused by mutations at each site using the site escape statistic specified by the interactive options at the bottom of the plot.
- The heatmaps show how each individual mutation affects each phenotype. The
x's indicate the amino-acid identity in the parental GPC strain, light gray indicates mutations that were not measured, and dark gray indicates mutations that are filtered out by one of the interactive sliders at the bottom of the plot (eg, they have a very negative effect on cell entry). You can mouse over any of the points for details. - The options at the bottom of the plot allow you to interactively adjust what is displayed. For instance, the minimum mutation entry in 293T cells only shows mutations with at least some minimal cell entry function (and grays out mutations that are more deleterious). You can also select to floor the escape at zero to show / not show "negative" escape values.
Click on the expansion box in the upper right of the plot to enlarge it for easier viewing, or click here to open the plot in a stand-alone window.