The construction and evaluation of blood transcription modules (BTM) is fully described in the Supplementary Note. The expression values of member genes in a module are combined into a single module activity score (the mean value). The module activity scores are used for subsequent analysis, such as Student t-test or Pearson correlation. All vaccine data were excluded from the BTM construction process. In antibody correlation analysis, the statistical significance of BTM modules was estimated by comparing to random permutation data, i.e., module memberships and sample labels were permutated to estimate the null distribution. Such significance is further enhanced when the same module is seen in two independent vaccine datasets. The analysis result with GSEA using BTM modules is comparable to that presented in this paper (Supplementary Table 3).
Day 30 polysaccharide specific IgG (sum of serogroup A and C) data subtracted by day 0 baseline were used for the antibody responses in MCV4 and MPSV4, as they were robust indicators throughout the study (Supplementary Fig. 1c). Day 30/0 anti-DT IgG data was used as DT specific response in MCV4. As previously reported, day 60 neutralizing antibody titers were used for the yellow fever vaccine 4 (link), and maximum fold change of hemagglutination inhibition (HAI) titers (day 28/0) were used for the influenza TIV vaccine 6 (link).