Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the RV144 Vaccine Efficacy Trial
Figure 2
Signature sites by HIV-1 protein.
All sites with evidence for a different amino acid distribution in vaccine versus placebo sequences relative to a reference residue (unadjusted p < 0.05) by any of the site-scanning methods DVE, GWJ, or MBS. Panel (A) depicts signature sites found in the full HIV-1 genome, including in vaccine-immunogen regions (relative to a vaccine immunogen sequence) and non-vaccine-immunogen regions (relative to the consensus AE sequence) and (B) depicts a more detailed view of the vaccine immunogen regions in Gag, Pol, and Env. The blue horizontal lines above the protein regions in panel (B) indicate the regions included in the vaccine immunogen sequences, and the blue lines below the Env protein region indicate the positions of the variable loops. Signature sites are indicated by red vertical lines, with a red point that is placed on the line as an indicator of the magnitude of the site’s test statistic using the GWJ method, which is a t statistic comparing substitution weights across treatment groups. For sites with multiple reference AAs, the red point indicates the largest magnitude of the multiple test statistics. The black dashed horizontal lines in the middle of the gene and protein regions indicate the zero-point for the test statistic, so the farther away the point is from the center line, the more significant it was observed to be with this method. Points above the dashed line indicate that a site was found to have a “vMatch” sieve effect, while points below the dashed line indicate “vMismatch” signature sites.